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optic nerve morphometry following axonal degeneration from saids in rhesus monkeys.in order to further study aids (acquired immunodeficiency syndrome) related neuropathologic findings, specifically progressive diffuse leuko-encephalopathy (pdl) and optic neuropathy, ten macaque monkeys (macaca mulatta) were infected with simian immunodeficiency virus (siv), observed for varying periods, and then sacrificed and tissue prepared for analysis. a marked difference from human aids pathology was found: in all monkeys, there was significant peripheral axonal dropout, as opposed to rel ...19947956315
cellular immune responses in rhesus macaques infected rectally with low dose simian immunodeficiency virus.monkeys infected rectally with low dose simian immunodeficiency virus (siv) were resistant to high dose challenge with siv. peripheral blood mononuclear cells (pbmc) from two of four challenged monkeys were unable to support siv replication in vitro unless cultures were depleted of cd8+ lymphocytes. monkeys that had survived high dose rectal infection with siv also suppressed virus replication in cultured pbmc. pbmc from uninfected monkeys supported virus replication in both unfractionated and c ...19947966226
infectivity of titered doses of simian immunodeficiency virus clone e11s inoculated intravenously into rhesus macaques (macaca mulatta).the macaque infectious dose (mid) of a single-cell clone of simian immunodeficiency virus isolated from a pig-tailed macaque (siv/mne clone e11s) was determined in rhesus macaques (macaca mulatta). twenty-one macaques were inoculated with 10-fold dilutions of the virus stock (three or four animals per dose). the virologic and clinical status of these animals was monitored for 26 weeks. the 25% mid (mid25) occurred at a 10(5)-fold dilution of the viral stock.19947966238
mucosal immunization with a live, virulence-attenuated simian immunodeficiency virus (siv) vaccine elicits antiviral cytotoxic t lymphocytes and antibodies in rhesus macaques.an effective aids vaccine must protect against sexual transmission of human immunodeficiency virus (hiv). therefore, vaccine regimens which stimulate antiviral immunity in the genital tract as well as in peripheral blood and systemic lymphoid tissues are needed. here, we describe a method of immunization by direct inoculation of the vaginal submucosa with a live attenuated siv, sivmac1a11. immunization by this route generated low levels of siv-specific igg and iga antibodies in serum and vaginal ...19947966240
induction of antigen-specific killer t lymphocyte responses using subunit sivmac251 gag and env vaccines containing qs-21 saponin adjuvant.subunit vaccines based on recombinant proteins have proved useful for inducing antibody responses and they are safe for widespread use because they do not contain any live components. unfortunately, they do not typically induce the types of cell-mediated immune responses required to control viral pathogens; specifically, they do not induce cd8+ cytotoxic t lymphocyte (ctl) responses. to increase the immunogenicity of recombinant proteins, we have used the qs-21 saponin adjuvant in subunit vaccin ...19947986590
the repertoire of cytotoxic t lymphocytes in the recognition of mutant simian immunodeficiency virus variants.the importance of the repertoire of a primed, aids virus-specific population of ctl in the recognition of emerging mutant viruses was assessed in simian immunodeficiency virus (siv)-infected rhesus monkeys. these studies were done by using the well-characterized ctl recognition of the sivmac gag peptide 11c (p11c) epitope in rhesus monkeys expressing the mhc class i molecule mamu-a*01. lysis of peptide-pulsed targets by bulk pbl effector cells from sivmac-infected, mamu-a*01+ monkeys was signifi ...19947989780
induction of humoral and cellular immunity to simian immunodeficiency virus: what are the requirements for protection?in an effort to produce a strong humoral and cellular immune response that might protect against simian immunodeficiency virus (siv) infection, groups of five rhesus macaques each were immunized intramuscularly at 0, 2 and 6 months with 100 micrograms of an inactivated preparation of siv/delta b670 in either an oil-in-water emulsion with ribi detox, containing mycobacterial cell wall skeleton and monophosphoryl lipid a (cws/mpl) (group a) or a water-in-oil emulsion with incomplete freund's adjuv ...19947998424
major histocompatibility complex class i-associated vaccine protection from simian immunodeficiency virus-infected peripheral blood cells.to evaluate the effectiveness of vaccine protection from infected cells from another individual of the same species, vaccinated rhesus macaques (macaca mulatta) were challenged with peripheral blood mononuclear cells from another animal diagnosed with acquired immune deficiency syndrome (aids). half of the simian immunodeficiency virus (siv)-vaccinated animals challenged were protected, whereas unprotected vaccinates progressed as rapidly to aids. protection was unrelated to either total antibod ...19948046353
early events in tissues during infection with pathogenic (sivmac239) and nonpathogenic (sivmac1a11) molecular clones of simian immunodeficiency virus.the extent of virus replication, tissue distribution, localization of virus within tissues, and the presence of pathological lesions was examined early after experimental infection of rhesus monkeys with simian immunodeficiency virus (siv). three strains of siv were used: molecularly cloned pathogenic sivmac239; molecularly cloned nonpathogenic sivmac1a11; and uncloned pathogenic sivmac. the major targets of infection in all animals at 2 weeks postinoculation were the thymus and spleen. the dist ...19948053500
mucosal infection of neonatal rhesus monkeys with cell-free siv.although the mechanisms for maternal transmission are unknown, approximately half of the infants congenitally infected with the human immunodeficiency virus type 1 (hiv-1) seem to become infected late in gestation or during delivery. previously, we have developed a rhesus monkey model for congenital infection by injecting cell-free simian immunodeficiency virus (siv) directly into amniotic fluid. our results suggested that fetal infection may have occurred via skin or mucous membrane exposure. m ...19948068415
intravaginal inoculation of rhesus macaques with cell-free simian immunodeficiency virus results in persistent or transient viremia.the simian immunodeficiency virus (siv)-rhesus macaque model of heterosexual human immunodeficiency virus transmission consists of atraumatic application of cell-free sivmac onto the intact vaginal mucosa of mature female rhesus macaques. this procedure results in systemic infection, and eventually infected animals develop the clinical signs and pathologic changes of simian aids. to achieve 100% transmission with the virus stocks used to date, multiple intravaginal inoculations are required. the ...19948083977
mucosal model of genital immunization in male rhesus macaques with a recombinant simian immunodeficiency virus p27 antigen.human immunodeficiency virus (hiv) can be transmitted through infected seminal fluid or vaginal or rectal secretions during heterosexual or homosexual intercourse. to prevent mucosal transmission and spread to the regional lymph nodes, an effective vaccine may need to stimulate immune responses at the genitourinary mucosa. in this study, we have developed a mucosal model of genital immunization in male rhesus macaques, by topical urethral immunization with recombinant simian immunodeficiency vir ...19948107223
incomplete protection, but suppression of virus burden, elicited by subunit simian immunodeficiency virus vaccines.we compared the efficacy of immunization with either simian immunodeficiency virus (siv) env glycoprotein (env), env plus gag proteins (gag-env), or whole inactivated virus (wiv), with or without recombinant live vaccinia vector (vv) priming, in protecting 23 rhesus macaques (six vaccine and two control groups) from challenge with sivmac251 clone bk28. vaccination elicited high titers of syncytium-inhibiting and anti-env (gp120/gp160) antibodies in all vaccinated macaques and anti-gag (p27) anti ...19948107246
upstream u3 sequences in simian immunodeficiency virus are selectively deleted in vivo in the absence of an intact nef gene.major transcriptional control elements are located within the u3 region of the long terminal repeats (ltrs) of lentivirus and other retroviral genomes. the nef auxiliary gene of simian immunodeficiency virus (siv) and human immunodeficiency virus overlaps about 70% of the 450- to 560-bp-long u3 region present in these primate lentiviruses. we analyzed viral dna sequences present in rhesus monkeys infected with a mutant of sivmac containing a 182-bp deletion in the region of nef that does not ove ...19948107267
cytopathologic and neurochemical correlates of progression to motor/cognitive impairment in siv-infected rhesus monkeys.neurochemical, pathologic, virologic, and histochemical correlates of simian immunodeficiency virus (siv)-associated central nervous system (cns) dysfunction were assessed serially or at necropsy in rhesus monkeys that exhibited motor and cognitive deficits after siv infection. some infected monkeys presented with signs of acquired immunodeficiency disease (aids) at the time of sacrifice. seven of eight animals exhibited motor skill impairment which was associated with elevated quinolinic acid i ...19948120538
molecular and biological characterization of simian immunodeficiency virus macaque strain 32h proviral clones containing nef size variants.the proviral genome of the 32h reisolate of simian immunodeficiency of macaques (sivmac32h) has been cloned and sequenced. including both long terminal repeats, it is 10277 base pairs in length and contains open reading frames for all known siv genes (gag, pol, vif, vpx, vpr, tat, rev, env and nef). this is the first report of an infectious sivmac molecular clone which contains no premature termination codons. three molecular clones of sivmac32h have been constructed differing in sequence only w ...19948126450
simian immunodeficiency virus as a model for vaccination against hiv. induction in rhesus macaques of gag- or nef-specific cytotoxic t lymphocytes by lipopeptides.the protection against infection by hiv probably requires the induction of both neutralizing abs and ctl responses. vaccination by attenuated hiv is hardly acceptable and the use of viral genes inserted in recombinant living vectors needs further development, especially with respect to safety. the peptidic vaccination is a promising approach but free peptides are usually poorly immunogenic. because potent immune responses have been obtained in mice with modified peptides such as lipopeptides, we ...19948133061
immunopathogenic events in acute infection of rhesus monkeys with simian immunodeficiency virus of macaques.infection of the rhesus monkey with simian immunodeficiency virus of macaques (sivmax) was employed to explore the early immune events associated with the initial containment of an acute aids virus infection. in nine rhesus monkeys infected intravenously with uncloned sivmac strain 251, high-level p27 plasma antigenemia was usually detected transiently from approximately day 7 through day 21 following virus inoculation. sivmac replication in lymph nodes measured by in situ rna hybridization clos ...19948139022
pathology and localization of simian immunodeficiency virus in the reproductive tract of chronically infected male rhesus macaques.despite the fact that human immunodeficiency virus (hiv) is transmitted by sexual contact, the biology of this mode of transmission remains largely undefined. hiv is present in semen in both cell-free and cell-associated forms and can be isolated from asymptomatic individuals and aids patients. the source of hiv in semen and the target cells for hiv transmission to men are unknown. epidemiologic studies have shown that in men, the presence of an intact foreskin is associated with increased risk ...19948139266
primary acute simian immunodeficiency virus infection of intestinal lymphoid tissue is associated with gastrointestinal dysfunction.human immunodeficiency virus (hiv)-associated intestinal abnormalities can occur before immunodeficiency or infection with opportunistic enteropathogens. rhesus macaques infected with simian immunodeficiency virus (siv) develop an aids-like illness that frequently includes enteropathy. the development of enteropathy and its association with siv infection in the intestinal tract was examined. by 1 week after infection, siv-infected macrophages and t lymphocytes were detected in gut-associated lym ...19948169404
immune responses induced by prototype vaccines for aids in rhesus monkeys.a battery of assay systems was used to profile both humoral and cell-mediated immune responses induced by immunization with candidate vaccines consisting of recombinant simian immunodeficiency virus (siv) glycoproteins rgp110 (nondenatured) with saf-m adjuvant (gp110 + saf-m) or rgp140 (denatured) with freund's adjuvant (gp140 + fa). all of the monkeys became infected after intravenous challenge. however, 16 days following infection, viral antigenemia was reduced in both groups of vaccinates com ...19948179961
intrathecal synthesis of igg in simian immunodeficiency virus (siv)-infected rhesus macaques (macaca mulatta).we examined cerebrospinal fluid (csf) and serum from 25 simian immunodeficiency (siv)-infected rhesus macaques for the presence of siv-specific immunoglobulin g (igg) and for intrathecal synthesis of igg. siv-specific igg was present in csf from almost 50% of the macaques. in approximately half of these animals the siv-specific igg appeared to be derived from serum by leakage across a disrupted blood-brain barrier, whereas in the remaining animals there was evidence of intrathecal igg synthesis. ...19948179966
the "v3" domain is a determinant of simian immunodeficiency virus cell tropism.thirty-one different mutant forms of simian immunodeficiency virus (sivmac) were created with changes in the region of env corresponding to the v3 domain of hiv-1. sixteen of these mutants had one amino acid change, 12 had two changes, two had three changes, and one had four changes in the sivmac "v3" loop. the ability of the mutant viruses to replicate in cemx174 cells, rhesus monkey peripheral blood mononuclear cells, and rhesus monkey alveolar macrophages was investigated. ten of the mutant v ...19948189506
in vitro susceptibility of macaca nemestrina to human herpesvirus 6: a potential animal model of coinfection with primate immunodeficiency viruses.human herpesvirus 6 (hhv-6), a lymphotropic herpesvirus, has been suggested as a potential cofactor in the acquired immunodeficiency syndrome (aids). previous studies indicate that hhv-6 has a restricted range of susceptible species. in this study, we tested the in vitro susceptibility to hhv-6 of macaca nemestrina (pig-tailed macaque), a species that has been found to be infectable by human immunodeficiency virus type i in vivo and that develops an aids-like syndrome following simian immunodefi ...19948198870
reduced virus load in rhesus macaques immunized with recombinant gp160 and challenged with simian immunodeficiency virus.as a safe alternative to inactivated and live-attenuated whole-virus siv vaccines, we have evaluated the potential of sivmac239 gp160 expressed by recombinant vaccinia virus (vsivgp160) and baculovirus (bsivgp160) to protectively immunize rhesus macaques against intravenous (i.v.) infection with pathogenic sivmac isolates. macaques were immunized with live vsivgp160 and/or bsivgp160 protein partially purified from insect cells. the challenge viruses, propagated in rhesus peripheral blood mononuc ...19948198872
titration and characterization of two rhesus-derived sivmac challenge stocks.simian immunodeficiency virus infection of macaques is a model for human immunodeficiency virus infection of humans. in vivo-titrated stocks of siv are essential for the utilization of this model for vaccine development. the elicitation of anti-human cell antibodies by some vaccines prepared in human cells and the related protective effects of the vaccine produced in human cells suggest a need for new macaque-derived siv stocks. here we describe the titration and characterization of two stocks o ...19948198874
emergence of antigenic variants of simian immunodeficiency virus (sivmac) in a seronegative macaque after sivmac239 infection.infection with the macaque strain of the simian immunodeficiency virus (sivmac) induces simian immunodeficiency syndrome in rhesus macaques. this report describes the isolation and identification of antigenic variants of sivmac in one of the infected monkeys (macaque #22803). eight naive rhesus monkeys were inoculated with a titered viral stock of the molecularly cloned sivmac239. standard serological analysis revealed that all but two were seroconverted. western blot analysis confirmed the sero ...19947787884
signs of kupffer cell involvement in productive simian immunodeficiency virus infection in monkey liver.the livers of 21 rhesus monkeys inoculated with sivmac251 were examined at 4 days to 39 months after infection. siv antigens were detected in the cytoplasm of kupffer cells (kc), macrophages and lymphocytes in two-thirds of the livers tested. the number of cells containing viral proteins substantially increased during the development of the disease, and kc were the main cell type displaying siv proteins at an advanced stage of infection. mature and immature lentiviral particles were found in cyt ...19947800950
development of malabsorption and nutritional complications in simian immunodeficiency virus-infected rhesus macaques.to assess the development and cause of malabsorption in rhesus macaques following experimental simian immunodeficiency virus (siv) infection and to evaluate its impact on nutritional status.19947802976
persistent infection with sivmac chimeric virus having tat, rev, vpu, env and nef of hiv type 1 in macaque monkeys.a chimeric human and simian immunodeficiency virus carrying the tat, rev, vpu, env, and nef genes of human immunodeficiency virus type 1 was generated. the chimeric virus, nm-3n, grew competently in peripheral blood mononuclear cells from cynomolgus monkeys like the parental sivmac. two cynomolgus monkeys and one rhesus monkey inoculated with nm-3n raised antibodies to sivmac gag and hiv-1 env. the antibodies raised in the cynomolgus monkeys persisted for at least 1.7 years. the antibodies conta ...19947811533
monocyte adhesion to endothelium in simian immunodeficiency virus-induced aids encephalitis is mediated by vascular cell adhesion molecule-1/alpha 4 beta 1 integrin interactions.because the mechanisms associated with recruitment of monocytes to brain in aids encephalitis are unknown, we used tissues from rhesus monkeys infected with simian immunodeficiency virus (siv) to examine the relative contributions of various adhesion pathways in mediating monocyte adhesion to endothelium from encephalitic brain. using a modified stamper and woodruff tissue adhesion assay, we found that the human monocytic cell lines, thp-1 and u937, and the b cell line, ramos, preferentially bou ...19947507300
an epitope in the v1 domain of the simian immunodeficiency virus (siv) gp120 protein is recognized by cd8+ cytotoxic t lymphocytes from an siv-infected rhesus macaque.cytotoxic t-lymphocyte (ctl) responses against the external envelope glycoprotein (gp120) of the simian immunodeficiency virus (siv) were studied in a rhesus macaque infected with sivmac/239. cd8+ t cells enriched from concanavalin a-stimulated peripheral blood mononuclear cells lysed autologous target cells infected with recombinant vaccinia virus vectors expressing the sivmac/239 or sivsm/h4 envelope protein, which share approximately 80% identity in amino acid sequence. a cd8+ ctl line derive ...19947511178
vaccine-induced neutralizing antibodies directed in part to the simian immunodeficiency virus (siv) v2 domain were unable to protect rhesus monkeys from siv experimental challenge.the potential of the simian immunodeficiency virus (siv) variable 2 (v2) domain as an effective region to boost siv-neutralizing antibodies and to protect against live siv challenge was tested in rhesus macaques. in this study, two rhesus macaques were primed with vaccinia virus recombinants expressing the surface glycoprotein gp140 of sivmac and were given booster injections with the sivmac v2 domain presented by a highly immunogenic carrier, the hepatitis b surface antigen (hbsag). the two vac ...19947521918
a simian immunodeficiency virus envelope v3 cytotoxic t-lymphocyte epitope in rhesus monkeys and its restricting major histocompatibility complex class i molecule mamu-a*02.the use of the simian immunodeficiency virus (siv) macaque model for assessing human immunodeficiency virus vaccine strategies will be facilitated by the characterization of predominant siv cytotoxic t-lymphocyte (ctl) epitopes and their restricting major histocompatibility complex (mhc) class i molecules in macaque species. we now define a rhesus monkey sivmac ctl epitope in the third hypervariable region of the envelope glycoprotein of the virus. this epitope, ynltmkcr, contains the first two ...19947521921
effects of u-75875, a peptidomimetic inhibitor of retroviral proteases, on simian immunodeficiency virus infection in rhesus monkeys.u-75875 inhibits human immunodeficiency virus types 1 and 2 and simian immunodeficiency virus (siv) proteases and blocks gag-pol protein processing and viral maturation and replication in vitro. rhesus monkeys were treated with vehicle alone or with formulated u-75875 at doses of 7 or 20 mg/kg of body weight per day for 26 days by continuous intravenous infusion beginning 6 h prior to intravenous inoculation with 10 monkey 50% infectious doses of siv delta b670, and the monkeys were monitored un ...19947522427
inhibition of simian immunodeficiency virus (siv) replication by cd8+ cells of siv-infected rhesus macaques: implications for immunopathogenesis.the ability of the cd8+ cells from simian immunodeficiency virus (siv)-infected rhesus macaques to inhibit siv replication was investigated. inhibition was produced by a heat-stable soluble factor of molecular size greater than 10kda. cd8+ supernatants from some macaques were found not only to suppress siv growth but also to be cytolytic toward both infected and uninfected cd4+ cells. such indiscriminate cd8+ cell-mediated cell killing may therefore account for dc4+ cell depletion in certain siv ...19947534828
t cell receptor v beta repertoire in an acute infection of rhesus monkeys with simian immunodeficiency viruses and a chimeric simian-human immunodeficiency virus.changes in t cell receptor (tcr) v beta repertoire and their correlation with virologic events were investigated in rhesus monkeys after acute infection with the simian immunodeficiency virus (siv). 11 genetically defined rhesus monkeys were experimentally infected with sivmac or a chimeric simian-human immunodeficiency virus (shiv), and their peripheral blood lymphocytes (pbl) and lymph nodes were prospectively assessed for tcr v beta gene expression. pbl and lymph nodes of the acutely infected ...19957540651
passive immunization of rhesus macaques against siv infection and disease.to evaluate the role of humoral immunity against simian immunodeficiency virus (siv), we tested whether passive immunization with plasma from sivmac251 vaccine-protected or healthy infected animals would protect rhesus monkeys against intravenous infection with ten 50% animal infectious doses of the cell-free homologous virus. the challenge dose of this sivmac251 virus stock had previously caused persistent infection in all (21 of 21) nonimmunized controls. a plasma pool was obtained from a dono ...19957546912
effects of viral virulence on intrauterine growth in siv-infected fetal rhesus macaques (macaca mulatta).studies with a simian immunodeficiency virus (siv)-infected fetal monkey model were conducted with a focus on fetal growth and viral pathogenesis. twenty-six fetuses were inoculated in utero via ultrasound guidance with an uncloned pathogenic strain of siv or vehicle during the second or third trimesters [gestational day (gd) 65, 110, or 130], sonographically monitored weekly (biometrics, blood flow), then necropsied at incremental time points postinfection. peripheral blood hematologic (complet ...19957552476
construction of human immunodeficiency virus 1/simian immunodeficiency virus strain mac chimeric viruses having vpr and/or nef of different parental origins and their in vitro and in vivo replication.we constructed a series of human immunodeficiency virus 1 (hiv-1)/simian immunodeficiency virus strain mac (sivmac) chimeric viruses having vpr and/or nef genes of either hiv-1 or sivmac based on a chimeric virus with ltrs, gag, pol, vif and vpx derived from sivmac and tar, rev, vpu and env from hiv-1. all of the chimeric viruses replicated in human and macaque peripheral blood mononuclear cells (pbmcs) and in several cd4+ human cell lines, though their growth potentials were slightly different ...19957561755
cellular immune response of rhesus monkeys infected with a partially attenuated nef deletion mutant of the simian immunodeficiency virus.to date the vaccines most successful in the simian immunodeficiency virus (siv) model of aids are live attenuated viruses. however, the virus-specific immune response induced after infection of monkeys with attenuated siv has not been described comprehensively. therefore, we investigated the cellular immune response of eight rhesus macaques infected with a nef deletion mutant of sivmac32h (pc8). in contrast to monkeys infected with pathogenic siv, pc8-infected macaques developed a virus-specific ...19957571408
serial passage of microglial siv results in selection of homogeneous env quasispecies in the brain.the pathogenic effects of hiv include infection of the central nervous system (cns) which can result in cognitive and motor dysfunction. simian immunodeficiency virus (siv) infection of rhesus macaques provides an excellent model of hiv-induced disease. we have achieved a reproducible infection of the cns using a stock of virus obtained by serial passage of microglia-associated siv. since the envelope genes of both hiv and siv encode determinants important in viral pathogenesis, and the variabil ...19957571415
gamma delta t cells in rhesus monkeys and their response to simian immunodeficiency virus (siv) infection.recent reports of the increase in peripheral blood gamma delta t cells in hiv+ patients prompted us to examine the gamma delta t cell system in rhesus monkeys (macaca mulatta) and the responses of these cells to siv infection. our results reveal differences in the gamma delta t cell subset composition and their expression of cd8 in the peripheral blood of monkeys and humans. the outgrowth of simian gamma delta t cells in response to daudi cells is similar to that in humans, but the exposure to i ...19957586674
constitutive expression of major histocompatibility complex class ii antigens on monocytes and b cells correlates with disease in simian immunodeficiency virus-infected rhesus macaques.constitutive host factors that influence progression to aids are understood poorly. in the macaque model for aids, 35 animals infected with simian immunodeficiency virus (siv) were analyzed for major histocompatibility complex class ii antigen expression on blood monocytes and b cells by immunostaining and flow cytometry. expression varied widely between animals but was constant with time. level of expression and the proportion of monocytes and b cells that expressed class ii were not affected b ...19957594662
vpr deletion mutant of simian immunodeficiency virus induces aids in rhesus monkeys.in previous experiments, animals infected with sivmac239 containing a point mutation in the vpr and nef genes developed aids-like symptoms after early reversion of the vpr and nef genes. here we show that two animals in which the nef gene but not the vpr gene had reverted in the first few months did not develop disease during a 3-year observation period even after reversion to a functional vpr gene 70 weeks postinfection. to study the influence of a stable vpr mutation on virus load and pathogen ...19957609047
repair and evolution of nef in vivo modulates simian immunodeficiency virus virulence.experimental evidence from the simian immunodeficiency virus (siv) model of aids has shown that the nef gene is critical in the pathogenesis of aids. consequently, nef is of considerable interest in both antiviral drug and vaccine development. preliminary findings in two rhesus macaques indicated that a deletion of only 12 bp found in the overlapping nef/3' long terminal repeat (ltr) region (9501 to 9512) of the sivmacc8 molecular clone was associated with reduced virus isolation frequency. we s ...19957609080
suppression of simian immunodeficiency virus replication by human immunodeficiency virus type 1 trans-dominant negative rev mutants.we demonstrate that trans-dominant negative rev mutants are able to suppress simian immunodeficiency virus provirus replication in both transient cotransfection assays and stably transduced hut 78 cells. these studies suggest that the efficacy of trans-dominant rev strategies in reducing viral burden may be evaluated in a simian immunodeficiency virus-rhesus macaque animal model.19957609088
squamous epithelial proliferative lesions associated with rhesus epstein-barr virus in simian immunodeficiency virus-infected rhesus monkeys.proliferative lesions were found on the squamous epithelium of the tongue, esophagus, or penis or haired skin of the lip, hand, or thorax of 8 simian immunodeficiency virus-infected rhesus monkeys that died of simian aids. the lesions were focal and consisted of hyperkeratosis, parakeratosis, and acanthosis in the skin, with additional ballooning degeneration in the tongue, esophagus, and penis. the epithelial surfaces were frequently colonized by candida species or gram-positive cocci. intranuc ...19957622899
infection of baboons with simian/human immunodeficiency viruses.baboons were evaluated for their utility to serve as a model for testing envelope-based vaccines against human immunodeficiency virus type 1 (hiv-1). the ability of hiv-1 strains iiib, rf, and sf2 to infect baboons was compared with that of simian/human immunodeficiency virus (shiv) recombinant viruses comprised of either hxb2 or sf2 env, tat, rev, and vpu genes inserted into the sivmac239 backbone. both shiv recombinants replicated in baboon pbmc in vitro, while no evidence of replication was n ...19957627620
in vivo administration of cd4-specific monoclonal antibody: effect on provirus load in rhesus monkeys chronically infected with the simian immunodeficiency virus of macaques.since monoclonal antibodies (mab) specific for cd4 are potent inhibitors of hiv and siv replication in vitro, we explored their potential usefulness in vivo as an aids therapy. the anti-cd4 mab 5a8 binds to domain 2 of the cd4 molecule and inhibits virus replication and virus-induced cell fusion at a postvirus binding step. administration of this mab to normal rhesus monkeys coats all circulating and lymph node cd4 cells and induces neither cd4 cell clearance nor measurable immunosuppression. in ...19957632466
a macaque adherent cell line that expresses human cd4 is susceptible to siv: utility for assessing neutralizing antibody.a macaque cd4 + adherent cell line was generated by stable expression of the human cd4 gene in a rhesus macaque mammary tumor cell line, cmmt. the resulting cell line cmmt/cd4 expressed surface cd4 and was sensitive to infection by a wide range of isolates of simian immunodeficiency virus (siv) of different subgroups, but was not susceptible to infection with hiv-1. the cmmt/cd4 cell line was used to develop a microassay for measurement of neutralizing antibody in plasma of siv-infected or immun ...19957635923
persistent infection of rhesus macaques with t-cell-line-tropic and macrophage-tropic clones of simian/human immunodeficiency viruses (shiv).to elucidate the functions of human immunodeficiency virus type 1 (hiv-1) genes in a nonhuman primate model, we have constructed infectious recombinant viruses (chimeras) between the pathogenic molecular clone of simian immunodeficiency virus (siv) sivmac239 and molecular clones of hiv-1 that differ in phenotypic properties controlled by the env gene. hiv-1sf33 is a t-cell-line-tropic virus which induces syncytia, and hiv-1sf162 is a macrophage-tropic virus that does not induce syncytia. a dna f ...19957638218
simian immunodeficiency virus (human hiv-ii) transmission in allograft bone procedures.infection of rhesus monkeys (macaca mulatta) with simian immunodeficiency virus (siv, hiv-ii) was used to study disease transmission in allograft bone. four allograft bone processing techniques--fresh, fresh frozen, double freeze-thaw, and double freeze-thaw with chemical decontamination--were evaluated.19957676330
morphological changes in lymph nodes and expression of vcam1 and cytokines at the late stages of siv-induced disease in rhesus monkeys.four patterns of structural alterations were found in lymph nodes (lns) from rhesus monkeys 17 to 34 months after infection with simian immunodeficiency virus (siv-mac251). siv p27gag antigen and viral particles were localized either between the processes of follicular dendritic cells (fdcs) or in the cytoplasm of macrophages. in hyperplastic follicles, enlarged germinal centres contained numerous ki67+ proliferating centroblasts which were rather rare in light zones occupied by the cd23+ fdc ne ...19957481091
both virus and host components are important for the manifestation of a nef- phenotype in hiv-1 and hiv-2.while it has been demonstrated that the nef protein of simian immunodeficiency virus is obligatory for the establishment of high viral loads and the development of simian aids in rhesus macaques, demonstrating a critical role for the human immunodeficiency virus (hiv) nef protein in tissue culture has been elusive. data have been contradictory as to whether nef has a negative or positive influence on in vitro virus replication. in an attempt to define a role for nef during virus propagation in t ...19957483259
identification of v3 mutations that can compensate for inactivating mutations in c4 of simian immunodeficiency virus.a valine to isoleucine substitution at position 322 within variable region 3 (v3) of envelope of simian immunodeficiency virus was previously shown to compensate for an inactivating valine to glycine mutation at position 448 in constant region 4 (c4) (morrison et al., virology 195, 167-174, 1993). cloned dna fragments with inactivating c4 mutations were combined with complex mixtures of mutant v3 sequences, and full length genomes were transfected into cos-1 cells. by cocultivating transfected c ...19957483261
the simian immunodeficiency virus transmembrane protein is poorly immunogenic in inactivated virus vaccine.the transmembrane proteins (tmp) of immunodeficiency lentiviruses are primary candidates for inclusion in aids vaccines, the design and testing of which is facilitated by the siv-macaque infection model. antibody responses to linear determinants in the sivmac tmp were investigated in rhesus macaques either infected with the sivmac j5 molecular clone or vaccinated with partially purified, formalin-inactivated sivmac. infected animals were shown to recognise predominantly four regions in the exter ...19957483761
characterization of a cd4-expressing macaque cell line that can detect virus after a single replication cycle and can be infected by diverse simian immunodeficiency virus isolates.primate lentiviruses such as human immunodeficiency virus (hiv) and simian immunodeficiency virus (siv) are phenotypically diverse, and virus isolates vary in cytopathicity, replication rate, and cell tropism. while all virus isolates infect primary peripheral blood lymphocytes, only a subset of strains infect established cd4-expressing t-cell lines. here, we describe the development and characterization of a macaque cell line that can be infected by all of the strains of siv that we have tested ...19957491763
limited viral spread and rapid immune response in lymph nodes of macaques inoculated with attenuated simian immunodeficiency virus.a comparative study was undertaken to characterize the very early events that distinguish attenuated and pathogenic simian immunodeficiency virus (siv) infections. three rhesus macaques were inoculated with the attenuated sivmac 251 delta nef virus, and three others with a virus of intermediate phenotype, sivmac 239 nef stop. they were compared to four macaques inoculated with the pathogenic sivmac 251 isolate. lymph nodes (ln) taken between 7 days and 2 months postinoculation were analyzed for ...19957491778
lymphocyte-tropic simian immunodeficiency virus causes persistent infection in the brains of rhesus monkeys.molecularly cloned sivmac239 is the prototypical sivmac lymphocyte-tropic virus that replicates productively in lymphocytes but poorly in macrophages. in macaques, the virus causes activation and productive infection of t lymphocytes which invade the central nervous system (cns) early after infection in the animal. however, infected animals develop immunosuppression and aids but rarely overt neurological disease. in this study, we examined multiple regions of the brain and spinal cord for the pr ...19957491784
highly attenuated hiv type 2 recombinant poxviruses, but not hiv-2 recombinant salmonella vaccines, induce long-lasting protection in rhesus macaques.immunization schemes employing priming with vector-based vaccine candidates followed by subunit booster administrations have been explored and shown to have merit in the human immunodeficiency virus type 1 (hiv-1) and simian immunodeficiency virus systems. in this study, we have assessed the priming capacity of highly attenuated poxvirus vector (nyvac and alvac)-based hiv-2 recombinants, as well as salmonella typhimurium hiv-2 recombinants in rhesus macaques. alvac- and nyvac-based vaccine candi ...19957492438
antiviral cytotoxic t lymphocytes in vaginal mucosa of simian immunodeficiency virus-infected rhesus macaques.the mucosal immune system of the female reproductive tract is of central importance for protection against sexually transmitted diseases, including hiv; however, this arm of the immune system remains poorly understood. antiviral ctl responses never have been documented in the genital tract and the role of ctl in this anatomic site is unknown. in this study, cd8+ intraepithelial lymphocytes (iel) in the vaginas of six simian immunodeficiency virus (siv)-infected female rhesus macaques were identi ...19957499875
t cell responses in macaques after vaginal immunization with particulate siv p27 antigen.rhesus monkeys were immunized by the vaginal and oral routes using a recombinant particulate simian immunodeficiency virus (siv) antigen. augmenting vaginal by oral immunization in macaques elicits proliferative cd4+ t cells in the circulation which are specific to the immunizing p27 antigen. reconstitution of enriched cd4+ t cells, b cells and macrophages from circulating mononuclear cells help b cells in specific iga anti-p27 antibody synthesis. the results suggest that augmented vaginal immun ...19957502859
a mhc class i b locus allele-restricted simian immunodeficiency virus envelope ctl epitope in rhesus monkeys.in light of the importance of virus-specific ctl in the control of the spread of the aids virus, it will be important to assess the generation of these effector cell responses in trials of novel vaccine strategies for the prevention of aids virus infections. to facilitate such studies in the simian immunodeficiency virus (siv)/macaque model for aids, we have defined a rhesus monkey sivmac ctl epitope carboxy terminus to both the cd4-binding and v4 regions of the envelope glycoprotein. we also us ...19957532670
simian immunodeficiency virus sivmac chimeric virus whose env gene was derived from siv-encephalitic brain is macrophage-tropic but not neurovirulent.we inoculated four rhesus macaques with molecularly cloned simian immunodeficiency virus sivmac239/17e env, a chimeric virus whose env gene was derived from the brain of an siv-encephalitic macaque. blood and lymphoid tissues had high frequencies of infected cells. the virus was neuroinvasive, but productive virus replication did not occur in the brain, and animals did not develop encephalitis.19957815523
induction of aids by simian immunodeficiency virus from an african green monkey: species-specific variation in pathogenicity correlates with the extent of in vivo replication.previous studies suggested that simian immunodeficiency viruses isolated from african green monkeys (sivagm) are relatively nonpathogenic. the report describes the isolation and biologic and molecular characterization of a pathogenic sivagm strain derived from a naturally infected african green monkey. this virus induced an aids-like syndrome characterized by early viremia, frequent thrombocytopenia, severe lymphoid depletion, opportunistic infections, meningoencephalitis, and death of five of e ...19957815563
zidovudine treatment prolongs survival and decreases virus load in the central nervous system of rhesus macaques infected perinatally with simian immunodeficiency virus.to assess the potential therapeutic effects of zidovudine, rhesus macaques were inoculated with simian immunodeficiency virus (siv) strain smm/b670 at birth and infused either continuously or intermittently with zidovudine for 6-7 months. zidovudine did not prevent infection but did significantly increase survival time, which was associated with lower serum p26 viral core antigen levels, a lower virus burden in the cerebrospinal fluid (csf), and lower csf quinolinic acid levels than in untreated ...19957797947
immediate zidovudine treatment protects simian immunodeficiency virus-infected newborn macaques against rapid onset of aids.simian immunodeficiency virus (siv) infection of newborn rhesus macaques is a practical animal model of pediatric aids. intravenous inoculation of rhesus newborns with uncloned sivmac resulted in a high virus load, no antiviral immune responses, severe immunodeficiency, and a high mortality rate within 3 months. in contrast, immediate oral zidovudine (azt) treatment of siv-inoculated rhesus newborns either prevented infection or resulted in reduced virus load, enhanced antiviral immune responses ...19957695293
cross-protective immune responses induced in rhesus macaques by immunization with attenuated macrophage-tropic simian immunodeficiency virus.the simian immunodeficiency virus (siv) macaque model of aids has provided a valuable system with which to investigate vaccine approaches for protection against human immunodeficiency virus type 1 (hiv-1) infection. in particular, the ability of macaques persistently infected with attenuated infectious molecular clones of siv to resist challenge with the pathogenic parental swarm has conclusively demonstrated that protective immunity can be achieved by immunization prior to exposure. the breadth ...19957707496
transfer of neuropathogenic simian immunodeficiency virus with naturally infected microglia.the central nervous system (cns) is a target for human immunodeficiency virus infection, and, in individuals with acquired immune deficiency syndrome, this can lead to a devastating dementia. only certain viral variants appear capable of invading the cns and infecting microglia and brain macrophages. to determine whether the virus entering the brain may be particularly pathogenic to the cns, we isolated microglia from the brains of simian immunodeficiency virus-infected rhesus monkeys. serial tr ...19957717458
simian immunodeficiency virus (siv)-specific ctl in cerebrospinal fluid and brains of siv-infected rhesus macaques.simian immunodeficiency virus (siv)-specific cd8+ ctl were isolated from blood, cerebrospinal fluid, and brains of rhesus macaques infected i.v. with siv. ctl were found as early as 1 wk postinfection and their appearance correlated with a decrease of viral ag (p27) found in the blood. ctl isolated from cerebrospinal fluid and/or brain often recognized different viral proteins than ctl isolated from blood, suggesting either a unique migratory pattern to the central nervous system or a difference ...19957730657
permissiveness of kupffer cells for simian immunodeficiency virus (siv) and morphological changes in the liver of rhesus monkeys at different periods of siv infection.the pathogenesis of liver injury, which remains unclear in the course of human immunodeficiency virus infection, can be investigated in simian immunodeficiency virus-infected macaques, which develop an immunodeficiency disease resembling human acquired immune deficiency syndrome (aids). we studied the livers of 21 monkeys infected with simian immunodeficiency virus (sivmac251) for 4 days to 39 months and detected viral antigens in kupffer cells, macrophages, and lymphocytes in 65% of the livers ...19957737626
early intrathecal events in rhesus macaques (macaca mulatta) infected with pathogenic or nonpathogenic molecular clones of simian immunodeficiency virus.encephalitis is a common and devastating sequela of hiv infection in humans and of simian immunodeficiency virus (siv) infection in rhesus macaques. we used the siv-infected rhesus macaque model to study early intrathecal events in the pathogenesis of lentiviral encephalitis.19957745949
rapid screening for mamu-a1-positive rhesus macaques using a sivmac gag peptide-specific cytotoxic t-lymphocyte assay.as part of an ongoing vaccine study using peptide immunogens designed to stimulate simian immunodeficiency virus (siv)mac-specific cytotoxic t lymphocytes (ctl) it was necessary to identify rhesus macaques within our colony bearing the mamu-a1 major histocompatibility complex (mhc) class i haplotype. peripheral blood mononuclear cells (pbmc) from individual monkeys were analysed by immunoelectrofocusing for the presence of a band corresponding to the mamu-a1 molecule. in addition, pbmc were puls ...19957751033
viral factors determine progression to aids in simian immunodeficiency virus-infected newborn rhesus macaques.to evaluate how viral variants may affect disease progression in human pediatric aids, we studied the potential of three simian immunodeficiency virus (siv) isolates to induce simian aids in newborn rhesus macaques. the three virus isolates were previously shown to range from pathogenic (sivmac251 and sivmac239) to nonpathogenic (sivmac1a11) when inoculated intravenously into juvenile and adult rhesus macaques. six newborn macaques inoculated with pathogenic, uncloned sivmac251 developed persist ...19957769679
repeated exposure of rhesus macaques to low doses of simian immunodeficiency virus (siv) did not protect them against the consequences of a high-dose siv challenge.as part of an in vivo titration study of the macaque simian immunodeficiency virus (sivmac) strain 251/spl, macaques were inoculated intravenously with various dilutions of this infectious sivmac. seven animals received dilutions from 10(-3) to 10(-6) of sivmac251/spl. two monkeys infected with the 10(-3) dilution of sivmac exhibited a productive infection as indicated by seroconversion, detection of genomic rna and proviral dna and positive virus isolation. these animals showed a cytotoxic t ce ...19957782761
an early increase in somatostatin mrna expression in the frontal cortex of rhesus monkeys infected with simian immunodeficiency virus.motor and cognitive impairment is common in human immunodeficiency virus disease in humans and simian immunodeficiency virus (siv) disease in rhesus monkeys. we have examined peptide neurotransmitter expression in the frontal cortex of siv-infected rhesus monkeys to identify alterations in cortical neurons that might explain this impairment. a 2-fold higher number of preprosomatostatin (srif) mrna-positive interneurons was observed in layer iv of frontal cortex in two separate cohorts of siv-inf ...19957877985
a vaccine-elicited, single viral epitope-specific cytotoxic t lymphocyte response does not protect against intravenous, cell-free simian immunodeficiency virus challenge.protection against simian immunodeficiency virus (siv) challenge was assessed in rhesus monkeys with a vaccine-elicited, single siv epitope-specific cytotoxic t-lymphocyte (ctl) response in the absence of siv-specific antibody. strategies were first explored for eliciting an optimal siv gag epitope-specific ctl response. these studies were performed in rhesus monkeys expressing the major histocompatibility complex (mhc) class i gene mamu-a*01, a haplotype associated with a predominant siv ctl ep ...19957884874
progression to aids in the absence of a gene for vpr or vpx.rhesus monkeys (macaca mulatta) were experimentally infected with strains of simian immunodeficiency virus (siv) derived from sivmac239 lacking vpr, vpx, or both vpr and vpx genes. these auxiliary genes are not required for virus replication in cultured cells but are consistently conserved within the sivmac/human immunodeficiency virus type 2/sivsm group of primate lentiviruses. all four rhesus monkeys infected with the vpr deletion mutant showed an early spike in plasma antigenemia, maintained ...19957884883
bone marrow monocyte/macrophages are an early cellular target of pathogenic and nonpathogenic isolates of simian immunodeficiency virus (sivmac) in rhesus macaques.hematopoietic abnormalities are a common complication of human immunodeficiency virus infection in humans. however, the pathogenesis of these abnormalities remains unclear. simian immunodeficiency virus (siv) infection of rhesus macaques is a well-recognized animal model for acquired immunodeficiency syndrome. our previous studies have determined that in early siv infection, rhesus macaques develop peripheral blood and bone marrow pathologic changes within the first 14 days after intravenous ino ...19957898051
hippocampal neuronal atrophy occurs in rhesus macaques following infection with simian immunodeficiency virus.there is strong evidence that patients with aids have loss of cortical neurons. in this study we have examined the hippocampus of rhesus monkeys infected with simian immunodeficiency virus (siv) to determine whether neuronal damage occurs in this model of human aids and to investigate its time course. twenty-eight infected monkeys (23 young [< 9 years] and five elderly [> 16 years]) were compared with 11 controls (six young and five elderly). numbers of nucleolated neurons per unit area of secti ...19958745242
low susceptibility of resident microglia to simian immunodeficiency virus replication during the early stages of infection.to assess the susceptibility of resident microglia to simian immunodeficiency virus (siv) infection, we analysed the brains of rhesus macaques after intracerebral (i.c.) inoculation of the virus into the central region at 7 days, 1, 2 and 3 months post-inoculation (p.i.). the brains of animals showed the same moderate neuropathological changes in central, frontal and parietal regions of the brain, characterized by gliosis, microglial nodules, perivascular infiltrates and occasional white matter ...19958745243
origins of simian immunodeficiency virus infection in macaques at the new england regional primate research center.a cohort of rhesus macaques (macaca mulatta), obtained from the california regional primate research center (crprc) and necropsied in 1970-72 with lesions suggestive of simian immunodeficiency virus (siv) infection, was identified at the new england regional primate research center (nerprc). polymerase chain reaction (pcr), dna sequence analysis, and in situ hybridization were used to confirm the presence of siv nucleic acids. this represents the earliest case of siv infection at the nerprc and ...19958751050
vcam-1 expression and leukocyte trafficking to the cns occur early in infection with pathogenic isolates of siv.this study reports on the endothelial expression of vascular cell adhesion molecule-1 (vcam-1) in the central nervous system (cns) early after experimental infection of rhesus monkeys (macaca mulatta) with pathogenic and nonpathogenic simian immunodeficiency virus (siv). diffuse endothelial expression of vcam-1 was observed in the cns in all animals receiving pathogenic siv. these findings demonstrate the rapidity with which pathogenic siv is able to enter the cns and induce endothelial cell act ...19958751051
assessing genetic-based therapies for aids using the simian immunodeficiency virus.a plasmid encoding the full-length infectious molecular proviral clone of sivmac239 was generated. virus derived from cells transfected with this clone replicated to high levels and was cytopathic for some transformed human cd4+ cell lines and primary rhesus macaque peripheral blood mononuclear cells. since replication of siv requires the functional expression of the viral encoded rev protein, transient co-transfection studies were initiated with the infectious proviral clone and a well-characte ...19958751053
follicular dendritic cells productively infected with immunodeficiency viruses transmit infection to t cells.lymphoid organs have been proposed to function as the major reservoir for the human immunodeficiency virus type 1 (hiv-1). within lymphatic tissues germinal centers represent foci of rapidly proliferating b cells governed by the interaction between b and t cells and follicular dendritic cells (fdc). accumulating evidence suggests an important role of fdc in the pathophysiology of the acquired immunodeficiency syndrome. direct proof for the infectibility of fdc with hiv-1 has been lacking until r ...19958577313
protection from hiv-1 envelope-bearing chimeric simian immunodeficiency virus (shiv) in rhesus macaques infected with attenuated siv: consequences of challenge.to determine whether prior infection with simian immunodeficiency virus (siv)bk28 protects macaques from subsequent exposure to an hiv-1 envelope chimeric siv (shiv). also, to determine the consequences of viral challenge on cd4 numbers and virus load on the current siv infection.19958605046
simian immunodeficiency virus (siv) gp130 oligomers protect rhesus macaques (macaca mulatta) against the infection with sivmac32h grown on t-cells or derived ex vivo.the efficacy of three sivmac32h gp130 vaccines was compared in rhesus monkeys. three rhesus monkeys were each immunized over a period of 20 weeks with a total of 600 microgram virion-derived gp130 oligomers (o-gp130) mixed with keyhole limpet hemocyanin and emulsified with incomplete freund's adjuvant. three other monkeys were infected with 5 x 10(8) pfu of vaccinia virus wild type (vv-wt) while three additional animals received an equivalent dose of vv expressing the gp130 of sivmac (vv-gp130). ...19968607276
efficient transcription and replication of simian immunodeficiency virus in the absence of nf-kappab and sp1 binding elements.ten mutants of the simian immunodeficiency virus (siv) sivmac239 bearing deletions (delta) or substitutions (subst) in the nf-kappab and/or sp1 binding elements were created, and the replicative capacities of the mutants were analyzed. all mutants, including one extensively mutagenized strain entirely missing the nf-kappab and four spl binding elements, replicated with wild-type kinetics and to a wild-type level in peripheral blood mononuclear cell cultures in 50 to 100% of the experiments. one ...19968627791
an env gene derived from a primary human immunodeficiency virus type 1 isolate confers high in vivo replicative capacity to a chimeric simian/human immunodeficiency virus in rhesus monkeys.to explore the roles played by specific human immunodeficiency virus type 1 (hiv-1) genes in determining the in vivo replicative capacity of aids viruses, we have examined the replication kinetics and virus-specific immune responses in rhesus monkeys following infection with two chimeric simian/human immunodeficiency viruses (shivs). these viruses were composed of simian immunodeficiency virus sivmac239 expressing hiv-1 env and the associated auxiliary hiv-1 genes tat, vpu, and rep. virus replic ...19968627800
polymyositis, arthritis, and uveitis in a macaque experimentally infected with human t lymphotropic virus type i.to establish a simian model of human t lymphotropic virus type i (htlv-i) infection and disease.19968630109
restriction of hiv-1 (subtype b) replication at the entry step in rhesus macaque cells.human immunodeficiency virus type 1 (hiv-1) is restricted for replication in rhesus macaque cells and does not establish infection in this species. the block to productive infection of macaque peripheral blood mononuclear cells (pbmc) in culture was investigated. a chimeric virus shiv containing hiv-1 tat, rev, and env and all other genes from a simian immunodeficiency virus clone pathogenic in macaques (i.e., sivmec239) replicated efficiently in macaque pbmc. thus, the attachment step, involvin ...19968638416
in vitro t lymphopoiesis of human and rhesus cd34+ progenitor cells.differentiation of hematopoietic progenitor cells into t lymphocytes generally occurs in the unique environment of the thymus, a feature that has hindered efforts to model this process in the laboratory. we now report that thymic stromal cultures from rhesus macaques can support t-cell differentiation of human or rhesus cd34+ progenitor cells. culture of rhesus or human cd34+ bone marrow-derived cells depleted of cd34+ lymphocytes on rhesus thymic stromal monolayers yielded cd3+cd4+cd8+, cd3+cd4 ...19968639759
vaccination of pregnant macaques protects newborns against mucosal simian immunodeficiency virus infection.simian immunodeficiency virus (siv) infection of newborn rhesus macaques is a rapid, sensitive animal model of human pediatric aids. newborn macaques were readily infected by uncloned sivmac following oral-conjunctival exposure and had persistently high viremia and rapid development of aids. in contrast, when 3 pregnant macaques were vaccinated against siv, 2 of the newborns that had transplacentally acquired antiviral antibodies were protected against mucosal siv infection at birth. these resul ...19968648204
vaccine protection by a triple deletion mutant of simian immunodeficiency virus.twelve rhesus monkeys were vaccinated with sivmac316 delta nef (lacking nef sequences), and 12 were vaccinated with sivmac239 delta3 (lacking nef, vpr, and upstream sequences in u3). sivmac316 and sivmac239 differ by only eight amino acids in the envelope; these changes render sivmac316 highly competent for replication in macrophages. seventeen of the animals developed persistent infections with the vaccine viruses. seven of the 24 vaccinated animals, however, developed infections that were appa ...19968648707
patterns of viral replication correlate with outcome in simian immunodeficiency virus (siv)-infected macaques: effect of prior immunization with a trivalent siv vaccine in modified vaccinia virus ankara.the dynamics of plasma viremia were explored in a group of 12 simian immunodeficiency virus (siv)-infected rhesus macaques (macaca mulatta) that had received prior immunization with either nonrecombinant or trivalent (gag-pol, env) siv-recombinant vaccinia viruses. three distinct patterns of viral replication observed during and following primary viremia accounted for significant differences in survival times. high-level primary plasma viremia with subsequently increasing viremia was associated ...19968648709
simian immunodeficiency virus dna vaccine trial in macaques.an experimental vaccine consisting of five dna plasmids expressing different combinations and forms of simian immunodeficiency virus-macaque (sivmac) proteins has been evaluated for the ability to protect against a highly pathogenic uncloned sivmac251 challenge. one vaccine plasmid encoded nonreplicating sivmac239 virus particles. the other four plasmids encoded secreted forms of the envelope glycoproteins of two t-cell-tropic relatives (sivmac239 and sivmac251) and one monocyte/macrophage-tropi ...19968648735
the effect of simian immunodeficiency virus infection in vitro and in vivo on the cytokine production of isolated microglia and peripheral macrophages from rhesus monkey.microglia are the major target for human immunodeficiency virus (hiv) infection within the central nervous system. because only a few cells are productively infected, it has been suggested that an aberrant cytokine production by this cell population may be an indirect mechanism leading to the development of neurological disorders in hiv-infected patients. therefore we decided to study the secretion pattern of several interleukins (il) by microglial cells and peripheral blood macrophages isolated ...19968661383
prolonged infection in rhesus macaques with simian immunodeficiency virus (sivmac239) results in animal-specific and rarely tissue-specific selection of nef variants.we analyzed the sequence of nef genes from different tissues of three rhesus macaques that had been infected with molecularly cloned sivmac239 for 88 to 92 weeks. comparison of the predicted amino acid sequences revealed that each macaque had selected out specific amino acid substitutions and that most of this variation (70%) was confined to four regions, amino acids 39 to 75, 90 to 105, 153 to 167, and 191 to 217, comprising 36% of the protein. the nef genes in these animals underwent extensive ...19968661405
whole body positron emission tomography imaging of simian immunodeficiency virus-infected rhesus macaques.pathogenesis of simian immunodeficiency virus (siv) infection in rhesus macaques begins with acute viremia and then progresses to a distributed infection in the solid lymphoid tissues, which is followed by a process of cellular destruction leading to terminal disease and death. blood and tissue specimens show the progress of infection at the cellular level but do not reveal the pattern of infection and host responses occurring throughout the body. the purpose of this investigation was to determi ...19968692831
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