Publications
| Title | Abstract | Year(sorted ascending) Filter | PMID Filter |
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| a dominant block to hiv-1 replication at reverse transcription in simian cells. | although nonhuman primates are genetically close to humans, their t cells do not support productive replication of hiv-1. in contrast, hiv-1 replicates in activated human cd4(+) t cells, monocytes, and metabolically active human cells of a variety of cell types become permissive for hiv-1 replication when transduced to express cd4 and ccr5 or cxcr4. the molecular basis of this species restriction to hiv-1 replication was investigated by using african green monkey and rhesus macaque cell lines th ... | 2002 | 12368468 |
| amino acid deletions are introduced into the v2 region of gp120 during independent pathogenic simian immunodeficiency virus/hiv chimeric virus (shiv) infections of rhesus monkeys generating variants that are macrophage tropic. | highly pathogenic simian immunodeficiency virus/hiv chimeric viruses (shivs) cause extremely rapid, irreversible, and systemic depletions of cd4(+) t lymphocytes in inoculated rhesus monkeys. in the absence of this t cell subset, virus production can be sustained for several months by tissue macrophage. during independent infections of seven animals with uncloned virus stocks, shiv variants emerged bearing amino acid deletions that affected specific residues of the gp120 v2 loop. some of these m ... | 2002 | 12370415 |
| elispot and elisa analysis of spontaneous, mitogen-induced and antigen-specific cytokine production in cynomolgus and rhesus macaques. | evaluation of cytokine production in macaques has been hampered by a lack of availability of optimized and standardized immunoassays such as elisa and enzyme-linked immune spot assay (elispot); only a limited number of macaque cytokines have been assessed by elispot. using monoclonal antibodies (mab) to human cytokines that cross-react with cynomolgus and rhesus macaque interferon-gamma (ifn-gamma), interleukin (il)-2, il-4, il-5, il-6, il-12, il-13 and granulocyte monocyte colony-stimulating fa ... | 2002 | 12379341 |
| live, attenuated simian immunodeficiency virus sivmac-m4, with point mutations in the env transmembrane protein intracytoplasmic domain, provides partial protection from mucosal challenge with pathogenic sivmac251. | attenuated molecular clones of simian immunodeficiency virus (sivmac) are important tools for studying the correlates of protective immunity to lentivirus infection in nonhuman primates. the most highly attenuated sivmac mutants fail to induce disease but also fail to induce immune responses capable of protecting macaques from challenge with pathogenic virus. we recently described a novel attenuated virus, sivmac-m4, containing multiple mutations in the transmembrane protein (tm) intracytoplasmi ... | 2002 | 12388697 |
| elicitation of simian immunodeficiency virus-specific cytotoxic t lymphocytes in mucosal compartments of rhesus monkeys by systemic vaccination. | since most human immunodeficiency virus (hiv) infections are initiated following mucosal exposure to the virus, the anatomic containment or abortion of an hiv infection is likely to require vaccine-elicited cellular immune responses in those mucosal sites. studying vaccine-elicited mucosal immune responses has been problematic because of the difficulties associated with sampling t lymphocytes from those anatomic compartments. in the present study, we demonstrate that mucosal cytotoxic t lymphocy ... | 2002 | 12388710 |
| escape in one of two cytotoxic t-lymphocyte epitopes bound by a high-frequency major histocompatibility complex class i molecule, mamu-a*02: a paradigm for virus evolution and persistence? | it is now accepted that an effective vaccine against aids must include effective cytotoxic-t-lymphocyte (ctl) responses. the simian immunodeficiency virus (siv)-infected rhesus macaque is the best available animal model for aids, but analysis of macaque ctl responses has hitherto focused mainly on epitopes bound by a single major histocompatibility complex (mhc) class i molecule, mamu-a*01. the availability of mamu-a*01-positive macaques for vaccine studies is therefore severely limited. further ... | 2002 | 12388723 |
| changes in dendritic cell migration and activation during siv infection suggest a role in initial viral spread and eventual immunosuppression. | dendritic cells (dc) serve an essential function in linking the innate and acquired immune responses to antigen. peripheral dc acquire antigen and migrate to draining lymph nodes, where they localize to the t cell-rich paracortex and function as potent antigen presenting cells. we examined the effects of human immunodeficiency virus (hiv) infection on dc function in vivo using the rhesus macaque/simian immunodeficiency virus (siv) model. our data show that during acute siv infection, langerhans ... | 2002 | 12390541 |
| whole inactivated siv virion vaccines with functional envelope glycoproteins: safety, immunogenicity, and activity against intrarectal challenge. | a novel type of whole inactivated simian immunodeficiency virus (siv) virion vaccine immunogen with functional envelope glycoproteins was evaluated, without adjuvant, in rhesus macaques. immunogens included purified inactivated virions of sivmac239, a designed mutant of sivmac239 with gp120 carbohydrate attachment sites deleted (sivmac239 g4,5), and sivmnee11s. the vaccines were noninfectious, safe, and immunogenic, inducing antibody responses and cellular responses, including responses by cd8+ ... | 2002 | 12390543 |
| protection by siv vlp dna prime/protein boost following mucosal siv challenge is markedly enhanced by il-12/gm-csf co-administration. | the ever increasing number of people infected by human immunodeficiency virus (hiv) throughout the world renders the development of effective vaccines an urgent priority. herein, we report on an attempt to induce and enhance antiviral responses using a deoxyribonucleic acid (dna) prime/virus-like particles (vlp) protein boost strategy adjuvanted with interleukin (il)-12/gm-csf in rhesus macaques challenged with simian immunodeficiency virus (siv). thus, groups of monkeys were administered three ... | 2002 | 12390544 |
| evaluation in rhesus macaques of tat and rev-targeted immunization as a preventive vaccine against mucosal challenge with shiv-bx08. | recent evidence suggests that a cd8-mediated cytotoxic t-cell response against the regulatory proteins of human immunodeficiency virus (hiv) or simian immunodeficiency virus (siv) may control infection after pathogenic virus challenge. here, we evaluated whether vaccination with tat or tat and rev could significantly reduce viral load in nonhuman primates. rhesus macaques were primed with semliki forest virus (sfv) expressing hiv-1 tat (sfv-tat) and hiv-1 rev (sfv-rev) and boosted with modified ... | 2002 | 12396607 |
| regulation of indoleamine 2,3-dioxygenase expression in simian immunodeficiency virus-infected monkey brains. | the human immunodeficiency virus type 1-associated cognitive-motor disorder, including the aids dementia complex, is characterized by brain functional abnormalities that are associated with injury initiated by viral infection of the brain. indoleamine 2,3-dioxygenase (ido), the first and rate-limiting enzyme in tryptophan catabolism in extrahepatic tissues, can lead to neurotoxicity through the generation of quinolinic acid and immunosuppression and can alter brain chemistry via depletion of try ... | 2002 | 12414962 |
| t-cell receptor:cd3 down-regulation is a selected in vivo function of simian immunodeficiency virus nef but is not sufficient for effective viral replication in rhesus macaques. | we investigated the function of severely truncated simian immunodeficiency virus (siv) nef proteins (tnef) in vitro and in vivo. these variants emerged in rhesus monkeys infected with sivmac239 containing a 152-bp deletion in the nef-unique region and have been suggested to enhance siv virulence (e. t. sawai, m. s. hamza, m. ye, k. e. shaw, and p. a. luciw, j. virol. 74:2038-2045, 2000). we found that the tnef proteins were unable to down-regulate the cell surface expression of major histocompat ... | 2002 | 12414978 |
| mamu-a*01 allele-mediated attenuation of disease progression in simian-human immunodeficiency virus infection. | expression of several major histocompatibility complex (mhc) class i alleles is associated with a protective effect against disease progression in both human immunodeficiency virus type 1 and simian immunodeficiency virus infection. to understand the mechanism underlying this effect, we investigated the expression of the mhc class i allele mamu-a*01 in simian-human immunodeficiency virus (shiv) infection, one of the major models for evaluation of aids vaccine candidates. we found that disease pr ... | 2002 | 12438610 |
| reactivation of a trypanosoma cruzi infection in a rhesus monkey (macaca mulatta) experimentally infected with siv. | trypanosoma cruzi-like flagellates were incidentally noted in blood smears of a routinely monitored rhesus monkey experimentally infected with the simian immunodeficiency virus (siv). immunodeficiency in the course of the siv infection reactivated a chronic infection of chagas' disease that had been unnoticed when the macaque was imported to europe. the animal developed no specific clinical symptoms of american trypanosomiasis, but histologically a chagasic myocarditis was detected. analysis of ... | 2002 | 12450203 |
| tenofovir treatment at 30 mg/kg/day can inhibit cortical bone mineralization in growing rhesus monkeys (macaca mulatta). | the acyclic nucleoside phosphonate analog, 9-[2-(r)-(phosphonomethoxy)propyl]adenine (pmpa; tenofovir: gilead sciences, inc., foster city, ca), has been shown to effectively inhibit simian immunodeficiency virus (siv) replication in rhesus macaques by blocking reverse transcription. however, chronic long-term tenofovir treatment at 30 mg/kg/day, intended to reduce viral replication and illness, has been shown to result in bone deformities and spontaneous fractures in rhesus monkeys. based on the ... | 2002 | 12472227 |
| rhesus monkey simian immunodeficiency virus infection as a model for assessing the role of selenium in aids. | the objective of this study was to determine whether simian immunodeficiency virus (siv) infection of macaques could be used as a model system to assess the role of selenium in aids. plasma and serum selenium levels were determined by standard assays in monkeys before and after inoculation of siv. siv-infected cells or cells expressing the hiv tat protein were labeled with 75se, and protein extracts were prepared and electrophoresed to analyze selenoprotein expression. total trna was isolated fr ... | 2002 | 12473832 |
| enhanced in vitro stimulation of rhesus macaque dendritic cells for activation of siv-specific t cell responses. | the macaque-simian immunodeficiency virus (siv) system is one of the best animal models available to study the role of dendritic cells (dcs) in transmission and pathogenesis of hiv, as well as to test dc-based vaccine and therapeutic strategies. to better define and optimize this system, the responsiveness of macaque monocyte-derived dcs to a variety of maturation stimuli was examined. characteristic immunophenotypic and functional dc maturation induced by standard monocyte conditioned medium (m ... | 2002 | 11792391 |
| replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity. | recent studies of human immunodeficiency virus type 1 (hiv-1) infection in humans and of simian immunodeficiency virus (siv) in rhesus monkeys have shown that resolution of the acute viral infection and control of the subsequent persistent infection are mediated by the antiviral cellular immune response. we comparatively assessed several vaccine vector delivery systems-three formulations of a plasmid dna vector, the modified vaccinia ankara (mva) virus, and a replication incompetent adenovirus t ... | 2002 | 11797011 |
| eventual aids vaccine failure in a rhesus monkey by viral escape from cytotoxic t lymphocytes. | potent virus-specific cytotoxic t lymphocyte (ctl) responses elicited by candidate aids vaccines have recently been shown to control viral replication and prevent clinical disease progression after pathogenic viral challenges in rhesus monkeys. here we show that viral escape from ctl recognition can result in the eventual failure of this partial immune protection. viral mutations that escape from ctl recognition have been previously described in humans infected with human immunodeficiency virus ... | 2002 | 11797012 |
| administration of recombinant rhesus interleukin-12 during acute simian immunodeficiency virus (siv) infection leads to decreased viral loads associated with prolonged survival in sivmac251-infected rhesus macaques. | the ability of recombinant rhesus interleukin-12 (rmamu-il-12) administration during acute simian immunodeficiency virus sivmac251 infection to influence the quality of the antiviral immune responses was assessed in rhesus macaques. group i (n = 4) was the virus-only control group. group ii and iii received a conditioning regimen of rmamu-il-12 (10 and 20 microg/kg, respectively, subcutaneously [s.c.]) on days -2 and 0. thereafter, group ii received 2 microg of il-12 per kg and group iii receive ... | 2002 | 11799168 |
| expression of dc-sign by dendritic cells of intestinal and genital mucosae in humans and rhesus macaques. | to better understand the role of dendritic cells (dcs) in human immunodeficiency virus (hiv) transmission at mucosal surfaces, we examined the expressions of the hiv adhesion molecule, dendritic-cell-specific icam-3 grabbing nonintegrin (dc-sign), its closely related homologue dc-signr, and hiv coreceptors by distinct dc populations in the intestinal and genital tracts of humans and rhesus macaques. we also developed monoclonal antibodies (mabs) specific for dc-sign or dc-signr. in the peyer's p ... | 2002 | 11799181 |
| recombinant canarypox vaccine-elicited ctl specific for dominant and subdominant simian immunodeficiency virus epitopes in rhesus monkeys. | since virus-specific ctl play a central role in containing hiv replication, a candidate aids vaccine should generate virus-specific ctl responses. in this study, the ability of a recombinant canarypox virus expressing siv gag-pol-env (alvac/siv gag-pol-env) was assessed for its ability to elicit both dominant and subdominant epitope-specific ctl responses in rhesus monkeys. following a series of five immunizations, memory ctl responses specific for a dominant gag epitope could be demonstrated in ... | 2002 | 11823518 |
| contribution of peaks of virus load to simian immunodeficiency virus pathogenesis. | the mechanisms causing aids and subsequently death in human immunodeficiency virus type 1 infection are not yet fully understood. nonetheless, correlates of accelerated progression to disease based on immunological and virological markers have been identified. the best correlate identified to date is the baseline virus load or the so-called viral set point. by focusing on a virus load measurement from a restricted time range, however, we ignore valuable information contained in the long-term pro ... | 2002 | 11836438 |
| fetal and maternal outcome after administration of tenofovir to gravid rhesus monkeys (macaca mulatta). | tenofovir has been shown to cross the placenta in quantities sufficient to sustain reductions in viral load in simian immunodeficiency virus (siv)-infected fetal monkeys. with chronic exposure (30 mg/kg), however, significant bone-related toxicity has been shown in approximately 25% of infants studied. further investigations were conducted to determine whether the bone-related toxicity observed was initiated during fetal life. gravid rhesus monkeys (n = 4) were administered tenofovir subcutaneou ... | 2002 | 11873070 |
| induction of mucosal protection against primary, heterologous simian immunodeficiency virus by a dna vaccine. | an effective vaccine against human immunodeficiency virus (hiv) should protect against mucosal transmission of genetically divergent isolates. as a safe alternative to live attenuated vaccines, the immunogenicity and protective efficacy of a dna vaccine containing simian immunodeficiency virus (siv) strain 17e-fr (siv/17e-fr) gag-pol-env was analyzed in rhesus macaques. significant levels of cytotoxic t lymphocytes (ctl), but low to undetectable serum antibody responses, were observed following ... | 2002 | 11884556 |
| generation of a life-expanded rhesus monkey fibroblast cell line for the growth of rhesus rhadinovirus (rrv). | rrv, the rhesus macaque equivalent to hhv-8 or kaposi's sarcoma-associated herpesvirus (kshv) was recently isolated from a simian immunodeficiency virus (siv) infected macaque with a lymphoproliferative disorder. the growth of rrv in tissue culture requires propagation of primary rhesus monkey fibroblasts (rfs). in an effort to extend the life of these primary cells in tissue culture, the catalytic subunit of telomerase (htert) was introduced into rf cells using a recombinant retrovirus. this ne ... | 2002 | 11890526 |
| development of anti-cd4 mab hu5a8 for treatment of hiv-1 infection: preclinical assessment in non-human primates. | the anti-cd4 mab 5a8 is a potent inhibitor of cd4-mediated infection of hiv-1. cd4 is obligatory for infection with primary hiv-1 isolates. humanized 5a8 (hu5a8) was constructed to reduce the potential immunogenicity and enhance the in vivo half-life when used in humans. hu5a8 is a molecularly engineered human igg4 antibody retaining the binding and functional properties of the murine version of 5a8 (mu5a8). this humanized mab has been shown to be very effective in inhibiting hiv-1 infection of ... | 2002 | 11893418 |
| the simian immunodeficiency virus deltanef vaccine, after application to the tonsils of rhesus macaques, replicates primarily within cd4(+) t cells and elicits a local perforin-positive cd8(+) t-cell response. | deletion of the nef gene from simian immunodeficiency virus (siv) strain sivmac239 yields a virus that undergoes attenuated growth in rhesus macaques and offers substantial protection against a subsequent challenge with some siv wild-type viruses. we used a recently described model to identify sites in which the sivdeltanef vaccine strain replicates and elicits immunity in vivo. a high dose of sivdeltanef was applied to the palatine and lingual tonsils, where it replicated vigorously in this por ... | 2002 | 11752159 |
| dominance of cd8 responses specific for epitopes bound by a single major histocompatibility complex class i molecule during the acute phase of viral infection. | cytotoxic t-lymphocyte (ctl) responses are thought to control human immunodeficiency virus replication during the acute phase of infection. understanding the cd8(+) t-cell immune responses early after infection may, therefore, be important to vaccine design. analyzing these responses in humans is difficult since few patients are diagnosed during early infection. additionally, patients are infected by a variety of viral subtypes, making it hard to design reagents to measure their acute-phase immu ... | 2002 | 11752176 |
| induction of anti-simian immunodeficiency virus cellular and humoral immune responses in rhesus macaques by peptide immunogens: correlation of ctl activity and reduction of cell-associated but not plasma virus load following challenge. | lipopeptides which carry the n-terminal moiety tripalmitoyl-s-glyceryl-cysteinyl-seryl-seryl (p(3)css) have been shown to have effective adjuvant and transmembrane carrier properties. to test the ability of these constructs to immunize against simian immunodeficiency virus [(siv)(mac)] infection, rhesus macaques, prescreened for expression of the mamu-a*01 mhc class i molecule, were immunized at regular intervals with lipopeptides corresponding to known siv(mac) ctl epitopes alone or in combinat ... | 2002 | 11752704 |
| alvac-siv-gag-pol-env-based vaccination and macaque major histocompatibility complex class i (a*01) delay simian immunodeficiency virus sivmac-induced immunodeficiency. | t-cell-mediated immune effector mechanisms play an important role in the containment of human immunodeficiency virus/simian immunodeficiency virus (hiv/siv) replication after infection. both vaccination- and infection-induced t-cell responses are dependent on the host major histocompatibility complex classes i and ii (mhc-i and mhc-ii) antigens. here we report that both inherent, host-dependent immune responses to sivmac251 infection and vaccination-induced immune responses to viral antigens wer ... | 2002 | 11739694 |
| alcohol unmasks simian immunodeficiency virus-induced cognitive impairments in rhesus monkeys. | alcohol and human immunodeficiency virus (hiv) produce similar neuropathological profiles, including loss of neurons in the frontal cortex. additionally, hiv-positive patients with a history of alcohol abuse have greater neurologic deficits, and chronic alcohol abuse produces electrophysiological deficits earlier in the hiv disease process. few studies, preclinical or clinical, have examined whether alcohol administration exacerbates the neuropsychological deficits in subjects with lentiviruses ... | 2002 | 12500109 |
| modulation of immunity and viral-host interactions by alcohol. | this manuscript represents the proceedings of a symposium at the 2001 rsa meeting in montreal, canada. the organizers/chairs were gyongyi szabo and geoffrey m. thiele. the presentations were (1) introduction, by gyongyi szabo; (2) chemokine dysregulation after acute ethanol exposure, by elizabeth j. kovacs; (3) chemokine production and innate immunity in the livers of simian immunodeficiency virus-infected macaca mulatta following chronic alcohol administration, by abraham p. bautista; (4) influ ... | 2002 | 12500115 |
| expression of il-18 by siv does not modify the outcome of the antiviral immune response. | interleukin 18 (il-18) is a proinflammatory cytokine expressed by several cell types, including activated dendritic cells and macrophages, that acts in synergy with il-12 as an important amplifying factor for ifn-gamma production and th1 development. to study the immunological and virological effects of il-18 expression in the context of a lentiviral infection, we inoculated rhesus macaques with a high dose of replication-competent simian immunodeficiency virus (siv) vectors carrying the rhesus ... | 2002 | 12490394 |
| how oestrogen or progesterone might change a woman's susceptibility to hiv-1 infection. | worldwide, 18.5 million women are infected with the human immunodeficiency virus (hiv-1). at least 80% of these hiv infections have occurred as a result of sexual intercourse with an infected male partner. this review focuses on how hiv-1 enters the human female reproductive tract, and how oestrogen or progesterone, by altering the cervicovaginal epithelium, might change a woman's susceptibility to hiv infection. experiments on hysterectomised rhesus monkeys suggest that the vagina, rather than ... | 2002 | 12495087 |
| effects of intestinal survival surgery on systemic and mucosal immune responses in siv-infected rhesus macaques. | evaluation of cellular immunity in the intestinal lamina propria of rhesus macaques has been used previously to assess protective immunity against mucosal simian immunodeficiency virus (siv) challenges. as this technique requires survival surgery to obtain jejunal tissue, effects of surgical stress on the immune system were investigated. siv-specific immune responses, including igg and iga binding antibodies in sera and mucosal secretions, igg and iga secreting cells in peripheral blood, igg neu ... | 2002 | 12519209 |
| vaccine development using the simian immunodeficiency virus model for aids. | a number of trials in primates using a wide range of putative vaccines based on simian immunodeficiency virus (siv) have been performed and are summarised here. | 2002 | 12566709 |
| simian-human immunodeficiency virus shiv89.6-induced protection against intravaginal challenge with pathogenic sivmac239 is independent of the route of immunization and is associated with a combination of cytotoxic t-lymphocyte and alpha interferon responses. | attenuated primate lentivirus vaccines provide the most consistent protection against challenge with pathogenic simian immunodeficiency virus (siv). thus, they provide an excellent model to examine the influence of the route of immunization on challenge outcome and to study vaccine-induced protective anti-siv immune responses. in the present study, rhesus macaques were immunized with live nonpathogenic simian-human immunodeficiency virus (shiv) 89.6 either intravenously or mucosally (intranasall ... | 2003 | 12584336 |
| turnover rates of b cells, t cells, and nk cells in simian immunodeficiency virus-infected and uninfected rhesus macaques. | we determined average cellular turnover rates by fitting mathematical models to 5-bromo-2'-deoxyuridine measurements in siv-infected and uninfected rhesus macaques. the daily turnover rates of cd4(+) t cells, cd4(-) t cells, cd20(+) b cells, and cd16(+) nk cells in normal uninfected rhesus macaques were 1, 1, 2, and 2%, respectively. daily turnover rates of cd45ra(-) memory t cells were 1%, and those of cd45ra(+) naive t cells were 0.5% for cd4(+) t cells and approximately 1% for cd4(-)cd45ra(+) ... | 2003 | 12594273 |
| experimental pneumocystis carinii pneumonia in simian immunodeficiency virus-infected rhesus macaques. | to establish experimental pneumocystis carinii infection in simian immunodeficiency virus (siv)-infected macaques as a model of acquired immunodeficiency syndrome (aids)-associated p. carinii pneumonia (pcp), siv-infected macaques were inoculated intrabronchially with macaque-derived p. carinii, and p. carinii-specific polymerase chain reaction (pcr) and flow cytometric analysis of bronchoalveolar lavage fluid were done biweekly for up to 44 weeks after inoculation. all inoculated animals had a ... | 2003 | 12599074 |
| prevalence of antibodies to selected viruses in a long-term closed breeding colony of rhesus macaques (macaca mulatta) in brazil. | the rhesus macaque breeding colony of the oswaldo cruz foundation (fiocruz) was established in 1932 from a founding stock of 100 animals. this population has remained closed to new animal introductions for almost 70 years. a serologic survey was performed to determine the prevalence of antibodies to selected viruses as a first approach to identifying viral pathogens endemic in this population. banked serum samples were tested for antibodies to simian immunodeficiency virus (siv), simian t-lympho ... | 2003 | 12619046 |
| nef gene is required for robust productive infection by simian immunodeficiency virus of t-cell-rich paracortex in lymph nodes. | the pathogenesis of aids virus infection in a nonhuman primate aids model was studied by comparing plasma viral loads, cd4(+) t-cell subpopulations in peripheral blood mononuclear cells, and simian immunodeficiency virus (siv) infection in lymph nodes for rhesus macaques infected with a pathogenic molecularly cloned sivmac239 strain and those infected with its nef deletion mutant (deltanef). in agreement with many reports, whereas sivmac239 infection induced aids and depletion of memory cd4(+) t ... | 2003 | 12634375 |
| the effect of chronic binge ethanol consumption on the primary stage of siv infection in rhesus macaques. | alcohol abuse and infection with hiv individually compromise immune function, but the consequence of both conditions together is poorly understood owing to the difficulties of performing appropriate studies in human subjects. simian immunodeficiency virus (siv) infection of rhesus macaques is considered to closely model hiv disease in that the virus infects cd4+ cells and this infection leads to a similar aids state. this study was initiated to study the combined effects of chronic binge alcohol ... | 2003 | 12658116 |
| global dysfunction of cd4 t-lymphocyte cytokine expression in simian-human immunodeficiency virus/siv-infected monkeys is prevented by vaccination. | human immunodeficiency virus type 1 infection results in a dysfunction of cd4(+) t lymphocytes. the intracellular events contributing to that cd4(+) t-lymphocyte dysfunction remain incompletely elucidated, and it is unclear whether aspects of that dysfunction can be prevented. the present studies were pursued in a rhesus monkey model of aids to explore these issues. loss of the capacity of peripheral blood cd4(+) t lymphocytes to express cytokines was first detected in simian immunodeficiency vi ... | 2003 | 12663776 |
| a replication competent adenovirus 5 host range mutant-simian immunodeficiency virus (siv) recombinant priming/subunit protein boosting vaccine regimen induces broad, persistent siv-specific cellular immunity to dominant and subdominant epitopes in mamu-a*01 rhesus macaques. | ctl are important in controlling hiv and siv infection. to quantify cellular immune responses induced by immunization, cd8(+) t cells specific for the subdominant env p15m and p54m epitopes and/or the dominant gag p11c epitope were evaluated by tetramer staining in nine macaques immunized with an adenovirus (ad) 5 host range mutant (ad5hr)-sivenv/rev recombinant and in four of nine which also received an ad5hr-sivgag recombinant. two ad5hr-siv recombinant priming immunizations were followed by t ... | 2003 | 12682263 |
| decreased ccr5 expression on cd4+ t cells of siv-infected sooty mangabeys. | sooty mangabeys are the natural host of simian immunodeficiency virus (sivsm). when injected into rhesus macaques, sivsm infection results in progressive declines in cd4(+) t cells, opportunistic infections, and aids. in contrast, siv-infected sooty mangabeys do not develop disease and live an apparently normal life span in captivity, despite maintaining high levels of virus in plasma throughout their lives. determining the mechanisms by which sooty mangabeys have evolved to resist disease progr ... | 2003 | 12689415 |
| optimal preparation of rhesus macaque blood for cytokine flow cytometric analysis. | the rhesus macaque is a common substitute for human subjects in many disease models, including simian immunodeficiency virus, the non-human primate equivalent of the human immunodeficiency virus. monoclonal antibodies and fluorochromes optimized for use in macaques were included in samples examined for immune responses with the use of intracellular cytokine flow cytometry (cfc). | 2003 | 12701130 |
| direct relationship between suppression of virus-specific immunity and emergence of cytomegalovirus disease in simian aids. | although opportunistic infections like cytomegalovirus (cmv) are common sequelae of end-stage aids, the immune events leading to cmv reactivation in human immunodeficiency virus (hiv)-infected individuals are not well defined. the role of cellular and humoral cmv-specific immune responses in immune control of latent cmv infection was evaluated prospectively in a cohort of 11 simian immunodeficiency virus (siv)-infected cmv-seropositive rhesus macaques, 6 of whom had histologic evidence of cmv di ... | 2003 | 12719568 |
| rhesus rhadinovirus infection in healthy and siv-infected macaques at tulane national primate research center. | rhesus rhadinovirus (rrv) infection was quantified in peripheral blood mononuclear cells (pbmc) from healthy and simian immunodeficiency virus (siv)-infected rhesus macaques (macaca mulatta) at the tulane national primate research center and in a large collection of simian acquired immunodeficiency syndrome--(saids)-associated lymphomas. quantification of rrv load was performed by real-time pcr using amplification primers specific for the rrv interleukin-6 homologue (rrv vil-6). rrv infection wa ... | 2003 | 12733596 |
| latent infection as a source of disseminated disease caused by organisms of the mycobacterium avium complex in simian immunodeficiency virus-infected rhesus macaques. | whether infection with mycobacterium avium complex (mac) among patients with acquired immune deficiency syndrome results from recent exposure to virulent strains or reactivation of latent infection acquired years earlier is unknown. to address this question, tissue samples from 47 simian immunodeficiency virus (siv)-infected and 63 siv-uninfected rhesus macaques were cultured. mac was cultured from 14 siv-uninfected macaques (22.2%) and 32 siv-infected macaques (68.1%); median bacterial burdens ... | 2003 | 12751032 |
| [electron microscopic investigation of cd4+ lymphocyte cell line c8166 after infection with simian immunodeficiency virus (siv)]. | the siv infection of rhesus macaques (macaca mulatta) is the most appropriate animal model in hiv research. the permanent human t-cell line c8166 is used for in vitro siv propagation. this paper describes ultrastructural features of the cells after infection with sivmac. the c8166 cells are ultrastructurally characterized by a heterogenous morphology which is independent of the infection. siv induced cell syncytia are observed 18 hours after infection. viral particles and budding occur 48 hours ... | 2003 | 12756953 |
| assessment of oral transmission using cell-free human immunodeficiency virus-1 in mice reconstituted with human peripheral blood leucocyte. | oral-genital contact is one of the risk factors for the transmission of human immunodeficiency virus (hiv) in adults. in recent reports, oral exposure to simian immunodeficiency virus (siv) was found to have important implications for the achievement of mucosal transmission of hiv in a rhesus monkey animal model. in the present study, we aimed first to establish a small animal model which did not develop tonsils suitable for hiv oral mucosa transmission, using non-obese diabetic/severe combined ... | 2003 | 12757623 |
| determinants of increased replicative capacity of serially passaged simian immunodeficiency virus with nef deleted in rhesus monkeys. | most rhesus macaques infected with simian immunodeficiency virus sivmac239 with nef deleted (either delta nef or delta nef delta vpr delta us [delta 3]) control viral replication and do not progress to aids. some monkeys, however, develop moderate viral load set points and progress to aids. when simian immunodeficiency viruses (sivs) recovered from two such animals (one delta nef and the other delta 3) were serially passaged in rhesus monkeys, the sivs derived from both lineages were found to co ... | 2003 | 12768002 |
| expression of simian immunodeficiency virus (siv) nef in astrocytes during acute and terminal infection and requirement of nef for optimal replication of neurovirulent siv in vitro. | as the most numerous cells in the brain, astrocytes play a critical role in maintaining central nervous system homeostasis, and therefore, infection of astrocytes by human immunodeficiency virus (hiv) or simian immunodeficiency virus (siv) in vivo could have important consequences for the development of hiv encephalitis. in this study, we establish that astrocytes are infected in macaques during acute siv infection (10 days postinoculation) and during terminal infection when there is evidence of ... | 2003 | 12768005 |
| simian immunodeficiency virus infection of cd4+cd8+ t cells in a macaque with an unusually high peripheral cd4+cd8+ t lymphocyte count. | we assessed the possible role in vivo cd4(+) cd8(+) t cells as a viral reservoir for simian immunodeficiency virus (siv), in a macaque with 50% cd4(+) cd8(+) t cells in peripheral blood. during primary infection (day 14) of this rhesus macaque with the pathogenic sivmac251 strain, proviruses were detected at similar frequencies in cd4(+) cd8(+) t cells (1/10) and cd4(+) t cells (1/10) and at a lower frequency in cd8(+) t cells (1/800). on day 235, no viral dna was detected in cd8(+) cells, despi ... | 2003 | 12804002 |
| viral escape from dominant simian immunodeficiency virus epitope-specific cytotoxic t lymphocytes in dna-vaccinated rhesus monkeys. | virus-specific cytotoxic t lymphocytes (ctl) are critical for control of human immunodeficiency virus type 1 replication. however, viral escape from ctl recognition can undermine this immune control. here we demonstrate the high frequency and pattern of viral escape from dominant epitope-specific ctl in siv gag dna-vaccinated rhesus monkeys following a heterologous simian immunodeficiency virus (siv) challenge. dna-vaccinated monkeys exhibited initial effective control of the siv challenge, but ... | 2003 | 12805435 |
| infection of macaques with simian immunodeficiency virus induces a species-specific antibody response to major histocompatibility complex class i and class ii molecules. | envelopes of retroviruses, including human immunodeficiency virus and simian immunodeficiency virus (siv), contain host cell proteins that potentially represent novel targets for vaccine development. we show here that sera from rhesus macaques recognized simian major histocompatibility complex (mhc) molecules in response to infection with siv. antibodies from these animals did not cross-react with human mhc antigens on mitogen-activated peripheral blood mononuclear cells. the development of anti ... | 2003 | 12810860 |
| new gene-based approaches for an aids vaccine. | vaccine approaches against aids have focused on inducing cellular immune responses, since many studies revealed the role of t cell responses in the control of human immunodeficiency virus or simian immunodeficiency virus (siv) infections. the experimental infection of rhesus macaques with siv or chimeric shiv is routinely used as a model for aids. in such models, dna immunization is a tool to elicit specific t cell responses and to study their protective efficacy. dna immunogenicity in primates ... | 2003 | 12818622 |
| quantitative evaluation of enterocytozoon bieneusi infection in simian immunodeficiency virus-infected rhesus monkeys. | the association of the microsporidia enterocytozoon bieneusi with chronic diarrhea and wasting in individuals with acquired immunodeficiency syndrome (aids) has been demonstrated. the disease caused by e. bieneusi has been linked to decreased levels of circulating cd4+ t lymphocytes. in this study, we investigated the relationship between the extent of excretion of e. bieneusi in feces of simian immunodeficiency virus (siv)-infected juvenile macaques and the cd4+ t lymphocyte counts in the perip ... | 2003 | 12823629 |
| truncated forms of human and simian immunodeficiency virus in infected individuals and rhesus macaques are unique or rare quasispecies. | truncated proviruses of variable sizes are present in peripheral blood mononuclear cells (pbmc) of human immunodeficiency virus type 1 (hiv-1)-infected persons and simian immunodeficiency virus (siv)-infected rhesus macaques. here, we investigated whether the highly deleted hiv and siv proviruses are present in infected organisms as multiple copies or whether each truncated provirus is unique. using end-point dilution, multiple long-distance (ld) dna pcr assays were run in parallel using dna ext ... | 2003 | 12832213 |
| heterogeneity of the simian immunodeficiency virus (siv) specific cd8(+) t-cell response in mucosal tissues during siv primary infection. | virus-specific cd8(+) t cells play an important role in controlling viral replication during acute primary infection. at this early stage, mucosal tissues represent a major site of viral replication. therefore, the presence of functional virus-specific cd8(+) effector t cells in the mucosa during primary infection is a key issue in the pathogenesis of infection. in order to evaluate the extent of this response, six rhesus macaques were infected with simian immunodeficiency virus (siv)mac251 and ... | 2003 | 12850201 |
| improved protection of rhesus macaques against intrarectal simian immunodeficiency virus siv(mac251) challenge by a replication-competent ad5hr-sivenv/rev and ad5hr-sivgag recombinant priming/gp120 boosting regimen. | in this study we investigated the ability of a replication-competent ad5hr-sivenv/rev and ad5hr-sivgag recombinant priming/gp120 boosting regimen to induce protective immunity in rhesus macaques against pathogenic simian immunodeficiency virus(mac251). immunization of macaques by two sequential administrations of the same recombinants by the same route resulted in boosting and persistence of siv-specific cellular immune responses for 42 weeks past the initial immunization. anti-siv gp120 immunog ... | 2003 | 12857905 |
| dna vaccination of macaques by a full-genome simian/human immunodeficiency virus type 1 plasmid chimera that produces non-infectious virus particles. | a dna vaccination regime was investigated previously in rhesus macaques using a full-genome human immunodeficiency virus type 1 (hiv-1) plasmid, which, due to mutations in the nucleocapsid (nc) proteins, produced only non-infectious hiv-1 particles (akahata et al., virology 275, 116-124, 2000). in that study, four monkeys were injected intramuscularly 14 times with the plasmid. all of them showed immunological responses against hiv-1 and partial protection from challenge with a simian immunodefi ... | 2003 | 12867656 |
| potent, persistent induction and modulation of cellular immune responses in rhesus macaques primed with ad5hr-simian immunodeficiency virus (siv) env/rev, gag, and/or nef vaccines and boosted with siv gp120. | immunity elicited by multicomponent vaccines delivered by replication-competent ad5hr-simian immunodeficiency virus (siv) recombinants was systematically investigated. rhesus macaques were immunized mucosally at weeks 0 and 12 with ad5hr-siv(smh4) env/rev, with or without ad5hr-siv(mac239) gag or ad5hr-siv(mac239) nef, or with all three recombinants. the total ad5hr dosage was comparably adjusted among all animals with empty ad5hr-deltae3 vector. the macaques were boosted with siv gp120 in monop ... | 2003 | 12885879 |
| high-throughput gene expression profiling indicates dysregulation of intestinal cell cycle mediators and growth factors during primary simian immunodeficiency virus infection. | during primary simian immunodeficiency virus (siv) infection, cd4+ t cells are severely depleted in gut-associated lymphoid tissue (galt), while cd8+ t-cell numbers dramatically increase. to gain an understanding of the molecular basis of this disruption in t-cell homeostasis, host gene expression was monitored in longitudinal jejunum tissue biopsies from siv-infected rhesus macaques by dna microarray analysis. transcription of cyclin e1, cdc2, retinoblastoma, transforming growth factor (tgf), f ... | 2003 | 12890623 |
| effect of humoral immune responses on controlling viremia during primary infection of rhesus monkeys with simian immunodeficiency virus. | cellular immune responses mediated by cd8+ lymphocytes exert efficient control of virus replication during primary simian immunodeficiency virus (siv) infection. however, the role that antibodies may play in the early control of virus replication remains unclear. to evaluate how antibody responses may affect virus replication during primary sivmac infection, we depleted rhesus monkeys of b cells with anti-cd20 antibody. in normal rhesus monkeys immunized with tetanus toxoid, anti-cd20 treatment ... | 2003 | 12525651 |
| mucosal priming of simian immunodeficiency virus-specific cytotoxic t-lymphocyte responses in rhesus macaques by the salmonella type iii secretion antigen delivery system. | nearly all human immunodeficiency virus (hiv) infections are acquired mucosally, and the gut-associated lymphoid tissues are important sites for early virus replication. thus, vaccine strategies designed to prime virus-specific cytotoxic t lymphocyte (ctl) responses that home to mucosal compartments may be particularly effective at preventing or containing hiv infection. the salmonella type iii secretion system has been shown to be an effective approach for stimulating mucosal ctl responses in m ... | 2003 | 12551977 |
| therapeutic dendritic-cell vaccine for simian aids. | an effective immune response against human immunodeficiency virus or simian immunodeficiency virus (siv) is critical in achieving control of viral replication. here, we show in siv-infected rhesus monkeys that an effective and durable siv-specific cellular and humoral immunity is elicited by a vaccination with chemically inactivated siv-pulsed dendritic cells. after three immunizations made at two-week intervals, the animals exhibited a 50-fold decrease of siv dna and a 1,000-fold decrease of si ... | 2003 | 12496959 |
| prevention of disease induced by a partially heterologous aids virus in rhesus monkeys by using an adjuvanted multicomponent protein vaccine. | recombinant protein subunit aids vaccines have been based predominantly on the virus envelope protein. such vaccines elicit neutralizing antibody responses that can provide type-specific sterilizing immunity, but in most cases do not confer protection against divergent viruses. in this report we demonstrate that a multiantigen subunit protein vaccine was able to prevent the development of disease induced in rhesus monkeys by a partially heterologous aids virus. the vaccine was composed of recomb ... | 2003 | 12502820 |
| reversion of the m184v mutation in simian immunodeficiency virus reverse transcriptase is selected by tenofovir, even in the presence of lamivudine. | the methionine-to-valine mutation in codon 184 (m184v) in reverse transcriptase (rt) of human immunodeficiency virus type 1 (hiv-1) or simian immunodeficiency virus (siv) confers resistance to (-)-2'-deoxy-3'-thiacytidine (3tc; lamivudine) and increased sensitivity to 9-[2-(phosphonomethoxy)propyl]adenine (pmpa; tenofovir). we have used the siv model to evaluate the effect of the m184v mutation on the emergence of resistance to the combination of 3tc plus pmpa. a site-directed mutant of sivmac23 ... | 2003 | 12502828 |
| control of viremia and prevention of simian-human immunodeficiency virus-induced disease in rhesus macaques immunized with recombinant vaccinia viruses plus inactivated simian immunodeficiency virus and human immunodeficiency virus type 1 particles. | an effective vaccine against the human immunodeficiency virus type 1 (hiv-1) will very likely have to elicit both cellular and humoral immune responses to control hiv-1 strains of diverse geographic and genetic origins. we have utilized a pathogenic chimeric simian-human immunodeficiency virus (shiv) rhesus macaque animal model system to evaluate the protective efficacy of a vaccine regimen that uses recombinant vaccinia viruses expressing simian immunodeficiency virus (siv) and hiv-1 structural ... | 2003 | 12502833 |
| a truncated form of nef selected during pathogenic reversion of simian immunodeficiency virus sivmac239deltanef increases viral replication. | the live, attenuated vaccine simian immunodeficiency virus sivmac239deltanef efficiently protects rhesus macaques against infection with wild-type sivmac but occasionally causes cd4(+) t-cell depletion and progression to simian aids (saids). virus recovered from a vaccinated macaque (rh1490) that progressed to saids had acquired an additional deletion in the nef gene, resulting in a frameshift that restored the original nef open reading frame (r. i. connor, d. c. montefiori, j. m. binley, j. p. ... | 2003 | 12502842 |
| convergent evolution of siv env after independent inoculation of rhesus macaques with infectious proviral dna. | the env gene of three simian immunodeficiency virus (siv) variants developed convergent mutations during disease progression in six rhesus macaques. the monkeys had been inoculated with supercoiled plasmids encoding infectious proviruses of sivmac239 (a pathogenic, wild-type strain), sivdelta3 (the live attenuated vaccine strain derived from sivmac239), or sivdelta3+ (a pathogenic progeny virus that had evolved from sivdelta3). all six monkeys developed immunodeficiency and progressed to fatal d ... | 2003 | 12919751 |
| distinct cycling cd4(+)- and cd8(+)-t-cell profiles during the asymptomatic phase of simian immunodeficiency virus sivmac251 infection in rhesus macaques. | elevated cd4 t-cell turnover may lead to the exhaustion of the immune system during human immunodeficiency virus type 1 (hiv-1) and simian immunodeficiency virus (siv) infections. however, this hypothesis remains controversial. most studies of this subject have concerned the blood, and information about the lymph nodes is rare and controversial. we used ki67 expression to measure cycling t cells in the blood and lymph nodes of uninfected macaques and of macaques infected with a pathogenic sivmac ... | 2003 | 12941915 |
| magnitude and diversity of cytotoxic-t-lymphocyte responses elicited by multiepitope dna vaccination in rhesus monkeys. | in an effort to develop an aids vaccine that elicits high-frequency cytotoxic-t-lymphocyte (ctl) responses with specificity for a diversity of viral epitopes, we explored two prototype multiepitope plasmid dna vaccines in the simian-human immunodeficiency virus/rhesus monkey model to determine their efficiency in priming for such immune responses. while a simple multiepitope vaccine construct demonstrated limited immunogenicity in monkeys, this same multiepitope genetic sequence inserted into an ... | 2003 | 12941922 |
| an in vivo replication-important function in the second coding exon of tat is constrained against mutation despite cytotoxic t lymphocyte selection. | human and simian immunodeficiency virus (hiv/siv) tat proteins are specified by two coding exons. tat functions in the transcription of primate lentiviruses. a plethora of in vitro data currently suggests that the second coding exon of tat is largely devoid of function. however, whether the second exon of tat contributes functionally to viral pathogenesis in vivo remains unknown. to address this question directly, we compared infection of rhesus macaques with an siv, engineered to express only t ... | 2003 | 12947089 |
| caspase-mediated apoptosis and cell death of rhesus macaque cd4+ t-cells due to cryopreservation of peripheral blood mononuclear cells can be rescued by cytokine treatment after thawing. | cryopreservation of peripheral blood mononuclear cells (pbmc) from animal model studies and clinical trials is utilized as a primary method for long-term storage of pbmc for future in vitro and in vivo applications. the objective of this study was to define the mechanistic pathways involved in cryopreservation-induced apoptosis of cd4+ t-cells in pbmc, and to evaluate a cytokine treatment of the cryopreserved samples to rescue apoptosis for the potential future use of the cryopreserved pbmc. usi ... | 2003 | 12963412 |
| use of interleukin 15 to enhance interferon-gamma production by antigen-specific stimulated lymphocytes from rhesus macaques. | the enzyme-linked immune spot (elispot) assay is receiving increased attention as a means for quantifying antigen-specific cd8 t-cell responses in rhesus macaques. further improving the sensitivity of this assay could aid in the evaluation of vaccine candidates and/or immune therapeutic candidates. interleukin (il)-15 has been demonstrated to stimulate expansion of human immunodeficiency virus (hiv)-specific cytotoxic t lymphocytes (ctl) and to regulate homeostatic proliferation of cd8+ memory c ... | 2003 | 12969547 |
| mother-to-infant transmission of siv via breast-feeding in rhesus macaques. | to decipher the mechanisms involved in oral transmission of human immunodeficiency virus/simian immunodeficiency virus (hiv/siv) through breast-feeding, we have developed an animal model using siv-infected lactating rhesus macaques (macaca mulatta) and their infants. five of eight macaque infants became infected during a 10-month study course after siv inoculation of lactating dams. in a second study, three of four chronically infected female macaques transmitted virus to their infants through b ... | 2003 | 14498978 |
| transient early post-inoculation anti-retroviral treatment facilitates controlled infection with sparing of cd4+ t cells in gut-associated lymphoid tissues in sivmac239-infected rhesus macaques, but not resistance to rechallenge. | like human immunodeficiency virus infection of humans, infection of rhesus macaques with pathogenic simian immunodeficiency virus (siv) strains typically results in persistent progressive infection, leading to clinically significant immunosuppression. in previous studies, we administered short term anti-retroviral treatment, shortly after intravenous inoculation with sivsme660, in an effort to allow immunologic sensitization under conditions not characterized by overwhelming cytopathic infection ... | 2003 | 14498980 |
| comparison of virology and immunology in shiv 89.6 proviral dna and virus-inoculated rhesus macaques. | inoculation of cats, goats and monkeys with plasmids encoding full-length proviral genomes results in persistent lentiviral infections. this system could be used as a method for administration of an attenuated human immunodeficiency virus (hiv) vaccine. here, we compare the virology and immunology in rhesus macaques inoculated with either simian/human immunodeficiency virus 89.6 (shiv 89.6) virus or a plasmid containing the shiv 89.6 proviral genome. there was a delay in appearance of systemic i ... | 2003 | 14498984 |
| expression of ifn-gamma induced cxcr3 agonist chemokines and compartmentalization of cxcr3+ cells in the periphery and lymph nodes of rhesus macaques during simian immunodeficiency virus infection and acquired immunodeficiency syndrome. | dysregulation of cytokines and chemokines during human immunodeficiency virus 1 (hiv-1) and simian immunodeficiency virus (siv) infection is thought to be critical in the progression of acquired immunodeficiency syndrome (aids). to evaluate the potential role of th1-agonist chemokines in disease progression during aids, we assessed cxcl9/mig and cxcl10/ip-10 expression simultaneously in the periphery and lymphoid tissues of siv-infected animals at a single-cell level by flow cytometry. we optimi ... | 2003 | 14498985 |
| early control of highly pathogenic simian immunodeficiency virus/human immunodeficiency virus chimeric virus infections in rhesus monkeys usually results in long-lasting asymptomatic clinical outcomes. | in contrast to simian immunodeficiency viruses (sivs), which induce immunodeficiency over a 1- to 2-year period, highly pathogenic simian-human immunodeficiency viruses (shivs) cause an irreversible and systemic depletion of cd4(+) t lymphocytes in macaque monkeys within weeks of inoculation. nonetheless, the seemingly more aggressive shivs have proven to be easier to control by the same vaccine regimens which fail to contain siv. because early events during in vivo infections may determine both ... | 2003 | 14512533 |
| the emergence and characterization of macrophage-tropic siv/hiv chimeric viruses (shivs) present in cd4+ t cell-depleted rhesus monkeys. | highly pathogenic simian immunodeficiency virus/human immunodeficiency virus type 1 chimeric viruses (shivs) induce an extremely rapid, systemic, and irreversible depletion of cd4+ t lymphocytes following their inoculation into rhesus macaques. confocal fluorescence microscopy was used to demonstrate that high levels of viremia in infected animals were sustained by virus-producing tissue macrophage (mphi) following the irreversible elimination of cd4+ t lymphocytes by highly pathogenic shivdh12r ... | 2003 | 14595005 |
| detection of antigen-specific t cell interferon gamma expression by elispot and cytokine flow cytometry assays in rhesus macaques. | both enzyme-linked immunospot (elispot) and cytokine flow cytometry (cfc) methods have been developed for the detection of low-frequency, antigen-specific, cytokine-producing t cells following short-term in vitro stimulation. peptide-based elispot and cfc assays were compared for the quantitative detection of interferon gamma-positive (ifn-gamma+) antigen-specific t cells in rhesus macaques. ten normal and nine simian immunodeficiency virus (siv)-infected monkeys were tested for the detection of ... | 2003 | 14604545 |
| genetic variation at the mitochondrial large-subunit rrna locus of pneumocystis isolates from simian immunodeficiency virus-infected rhesus macaques. | the nucleotide sequences of a segment of the pneumocystis mitochondrial large-subunit (mt lsu) rrna gene from rhesus macaques coinfected with simian immunodeficiency virus (siv) and pneumocystis carinii were examined. of 12 isolates examined, 3 were found to be identical and the others showed substantial sequence variation, with up to 13% divergence among variants. we identified two general sequence types that differed at several sites, including a conserved 26-nucleotide insertion. four monkeys ... | 2003 | 14607864 |
| use of a small molecule ccr5 inhibitor in macaques to treat simian immunodeficiency virus infection or prevent simian-human immunodeficiency virus infection. | human immunodeficiency virus type 1 (hiv-1) fuses with cells after sequential interactions between its envelope glycoproteins, cd4 and a coreceptor, usually cc chemokine receptor 5 (ccr5) or cxc receptor 4 (cxcr4). cmpd 167 is a ccr5-specific small molecule with potent antiviral activity in vitro. we show that cmpd 167 caused a rapid and substantial (4-200-fold) decrease in plasma viremia in six rhesus macaques chronically infected with simian immunodeficiency virus (siv) strains sivmac251 or si ... | 2003 | 14623909 |
| human immunodeficiency virus type 1 vif supports efficient primate lentivirus replication in rhesus monkey cells. | human immunodeficiency virus type 1 (hiv-1) and simian immunodeficiency virus (siv) vif share limited homology and display species-specific activity, leading to speculation that vif sequences could determine the block in hiv-1 replication in rhesus monkeys. to address this issue, we engineered a novel siv recombinant in which hiv-1 vif replaced siv vif in a sivmac239 background. insertion of hiv-1 vif into the siv vif locus did not produce a replication-competent virus. therefore, we inserted hi ... | 2003 | 14645904 |
| productive infection of dendritic cells by simian immunodeficiency virus in macaque intestinal tissues. | dendritic cells (dcs) are potent antigen-presenting cells that likely play multiple roles in human immunodeficiency virus-1 (hiv-1) and simian immunodeficiency virus (siv) pathogenesis. this paper describes the effects of pathogenic siv infection on the networks of dcs in rhesus macaque (macaca mulatta) intestinal tissues. intestinal tissues were obtained from macaques at different stages of disease following infection with the pathogenic siv/deltab670 isolate. the patterns and levels of express ... | 2003 | 14648666 |
| adenovirus-transduced dendritic cells injected into skin or lymph node prime potent simian immunodeficiency virus-specific t cell immunity in monkeys. | adenoviral vectors can be used to deliver complex ag to dendritic cells (dc), and thus may be ideal for stimulating broad t cell responses to viral pathogens and tumors. to test this hypothesis in a relevant primate model, we used recombinant adenovirus serotype 5 vectors expressing siv gag ag to transduce monocyte-derived dc from rhesus macaques, and then immunized donor animals either by intradermal or intranodal injections. t cell responses were evaluated by elispot assay using previously fro ... | 2003 | 14662894 |
| evidence for antibody-mediated enhancement of simian immunodeficiency virus (siv) gag antigen processing and cross presentation in siv-infected rhesus macaques. | by using the dominant simian immunodeficiency virus (siv) gag mamu-a01 restricted major histocompatibility complex (mhc) class i epitope p11cm, we demonstrate antibody-mediated enhanced mhc class i cross presentation of siv gag. in vitro restimulation of peripheral blood mononuclear cells from siv-infected rhesus macaques with recombinant full-length siv gag p55 plus p55 affinity-purified immunoglobulin g (p55 gag/p55-igg) led to the generation of markedly higher frequencies of p11cm specific pr ... | 2003 | 12477806 |
| immunization of newborn rhesus macaques with simian immunodeficiency virus (siv) vaccines prolongs survival after oral challenge with virulent sivmac251. | there is an urgent need for active immunization strategies that, if administered shortly after birth, could protect infants in developing countries from acquiring human immunodeficiency virus (hiv) infection through breast-feeding. better knowledge of the immunogenic properties of vaccine candidates in infants and of the effect of maternal antibodies on vaccine efficacy will aid in the development of such a neonatal hiv vaccine. simian immunodeficiency virus (siv) infection of infant macaques is ... | 2003 | 12477823 |
| importance of b-cell responses for immunological control of variant strains of simian immunodeficiency virus. | the properties of three variants of cloned simian immunodeficiency virus strain 239 (siv239) were compared. one strain (m5) lacked five sites for n-linked carbohydrate attachment in variable regions 1 and 2 (v1 and v2) of the gp120 envelope protein, one strain (deltav1-v2) completely lacked v1 and v2 sequences, and another (316) had nine mutations in the envelope that impart high replicative capacity for tissue macrophages. all three strains were capable of significant levels of fusion independe ... | 2003 | 12477842 |
| impact of simian immunodeficiency virus (siv) infection on lymphocyte numbers and t-cell turnover in different organs of rhesus monkeys. | hiv infection leads to reduced numbers and increased turnover of cd4(+) t cells in blood. however, blood represents only 2% of the total lymphocyte pool, and information about other organs is lacking, leading to controversy about the effects of hiv infection on t-cell homeostasis. therefore, we have determined phenotype and turnover of lymphocyte subsets in various tissues of macaques. infection with simian immunodeficiency virus (siv) resulted in increased proliferation rates of t cells in all ... | 2003 | 12393472 |
| modeling a safer smallpox vaccination regimen, for human immunodeficiency virus type 1-infected patients, in immunocompromised macaques. | we have modeled smallpox vaccination with dryvax (wyeth) in rhesus macaques that had depletion of cd4(+) t cells induced by infection with simian immunodeficiency virus or simian/human immunodeficiency virus. smallpox vaccination induced significantly larger skin lesions in immunocompromised macaques than in healthy macaques. unexpectedly, "progressive vaccinia" was infrequent. vaccination of immunocompromised macaques with the genetically-engineered, replication-deficient poxvirus nyvac, before ... | 2003 | 14551889 |
| caspase-dependent and -independent t-cell death pathways in pathogenic simian immunodeficiency virus infection: relationship to disease progression. | studies of human immunodeficiency virus (hiv) and nonhuman primate models of pathogenic and nonpathogenic simian immunodeficiency virus (siv) infections have suggested that enhanced ex vivo cd4 t-cell death is a feature of pathogenic infection in vivo. however, the relative contributions of the extrinsic and intrinsic pathways to programmed t-cell death in siv infection have not been studied. we report here that the spontaneous death rate of cd4+ t cells from pathogenic sivmac251-infected rhesus ... | 2003 | 14576776 |
| high frequency of virus-specific cd8+ t cells in the central nervous system of macaques chronically infected with simian immunodeficiency virus sivmac251. | infection with human immunodeficiency virus or simian immunodeficiency virus (siv) induces virus-specific cd8(+) t cells that traffic to lymphoid and nonlymphoid tissues. in this study, we used gag-specific tetramer staining to investigate the frequency of cd8(+) t cells in peripheral blood and the central nervous system of mamu-a*01-positive siv-infected rhesus macaques. most of these infected macaques were vaccinated prior to sivmac251 exposure. the frequency of gag(181-189) cm9 tetramer-posit ... | 2003 | 14581571 |
| high attenuation and immunogenicity of a simian immunodeficiency virus expressing a proteolysis-resistant inhibitor of nf-kappab. | nf-kappab/ikappab proteins play a major role in the transcriptional regulation of human immunodeficiency virus, type-1 (hiv-1). in the case of simian immunodeficiency virus (siv) the cellular factors required for the viral transcriptional activation and replication in vivo remain undefined. here, we demonstrate that the p50/p65 nf-kappab transcription factors enhanced the tat-mediated transcriptional activation of sivmac239. in addition, ikappab-alpha s32/36a, a proteolysis-resistant inhibitor o ... | 2004 | 14593121 |
| cytotoxic t lymphocytes in protection against equine infectious anemia virus. | cytotoxic t lymphocytes (ctl) are associated with virus control in horses infected with equine infectious anemia virus (eiav). early in infection, control of the initial viremia coincides with the appearance of ctl and occurs before the appearance of neutralizing antibody. in carrier horses, treatment with immunosuppressive drugs results in viremia before a change in serum neutralizing antibody occurs. clearance of initial viremia caused by other lentiviruses, including human immunodeficiency vi ... | 2004 | 15984338 |
| use of a replication-defective vector to track cells initially infected by siv in vivo: infected mononuclear cells rapidly appear in the draining lymph node after intradermal inoculation of rhesus monkeys. | a better understanding of the mechanisms of hiv dissemination, a key step in pathogenesis, would be possible if the cellular pathways of viral dissemination could be followed in simian immunodeficiency virus (siv)- inoculated monkeys or hiv-infected people. in an initial attempt to follow this process using a traceable virus infection, we inoculated rhesus monkeys intradermally (id) or directly into lymph nodes with a replication-defective siv-based vector expressing the enhanced jellyfish green ... | 2004 | 15650422 |