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motor evoked potentials in a rhesus macaque model of neuro-aids.previous work using bone marrow passaged sivmac239 (simian immunodeficiency virus) has shown that macrophage tropic strains of this virus enter the rhesus macaque brain early following inoculation (sharma et al, 1992; desrosiers et al, 1991; zhu et al, 1995; and narayan et al, 1997). as part of an effort to more fully characterize the extent of neurologic impairment associated with siv infection of the brain, we used transcranial electrical stimulation of motor cortex and the spinal cord to evok ...199910414512
induction of mucosal antibody responses by microsphere-encapsulated formalin-inactivated simian immunodeficiency virus in a male urethral challenge model.male rhesus macaques were immunized mucosally with microsphere-encapsulated formalin-inactivated simian immunodeficiency virus (siv) particles in a test of immunogenicity and protection against mucosal siv challenge. tracheal boosting of animals that had been primed intramuscularly resulted in strong serum elisa titers to siv, and evidence of local iga responses in broncho-alveolar washes. the bulk of the antibody response was against non-envelope epitopes. no neutralizing antibody was observed, ...199910438051
factors associated with slow disease progression in macaques immunized with an adenovirus-simian immunodeficiency virus (siv) envelope priming-gp120 boosting regimen and challenged vaginally with sivmac251.rhesus macaques were immunized with a combination vaccine regimen consisting of adenovirus type 5 host range mutant-simian immunodeficiency virus envelope (ad5hr-sivenv) recombinant priming and boosting with native siv gp120. upon intravaginal challenge with sivmac251, both persistently and transiently viremic animals were observed (s. l. buge, e. richardson, s. alipanah, p. markham, s. cheng, n. kalyan, c. j. miller, m. lubeck, s. udem, j. eldridge, and m. robert-guroff, j. virol. 71:8531-8541, ...199910438833
effective induction of simian immunodeficiency virus-specific cytotoxic t lymphocytes in macaques by using a multiepitope gene and dna prime-modified vaccinia virus ankara boost vaccination regimen.dna and modified vaccinia virus ankara (mva) are vaccine vehicles suitable and safe for use in humans. here, by using a multicytotoxic t-lymphocyte (ctl) epitope gene and a dna prime-mva boost vaccination regimen, high levels of ctls specific for a single simian immunodeficiency virus (siv) gag-derived epitope were elicited in rhesus macaques. these vaccine-induced ctls were capable of killing siv-infected cells in vitro. fluorescence-activated cell sorter analysis using soluble tetrameric major ...199910438842
induction of inhibitory antibodies to the ccr5 chemokine receptor and their complementary role in preventing siv infection in macaques.the seven-transmembrane g-protein-linked ccr5 molecule functions as a major coreceptor for hiv or simian immunodeficiency virus (siv) infection. antibodies to ccr5 were studied in rhesus macaques immunized with siv grown in human cd4(+) t cells. these macaques were completely protected against i.v. challenge with live siv. sera from the protected macaques showed significantly greater inhibition of siv replication (p < 0.001) and macrophage inflammatory protein-1beta-generated ccr5-dependent chem ...199910458756
combined systemic and mucosal immunization with microsphere-encapsulated inactivated simian immunodeficiency virus elicits serum, vaginal, and tracheal antibody responses in female rhesus macaques.we determined the efficacy of immunization with microsphere-encapsulated whole inactivated simian immunodeficiency virus (siv) by combined systemic and mucosal administration to protect female rhesus macaques against vaginal challenge with homologous rhesus pbmc-grown sivmac251. animals in one group were primed and boosted intramuscularly. two groups were primed intramuscularly and boosted either intratracheally or orally. a final group was primed by vaccinia/rgp140 scarification and subdivided ...199910461832
neutralizing antibody responses in africa green monkeys naturally infected with simian immunodeficiency virus (sivagm).this study assessed the magnitude and cross-reactivity of the neutralizing antibody response generated by natural siv infection in wild-caught african green monkeys. neutralizing antibodies of variable potency, sometimes exceeding a titer of 1:1,000, were detected in 20 of 20 siv-seropositive african green monkeys in kenya. detection of those neutralizing antibodies was dependent on the strain of virus and the cells used for assay, where the most sensitive detection was made with sivagm1532 in s ...199910475110
motor skill impairment in siv-infected rhesus macaques with rapidly and slowly progressing disease.a number of studies have shown that simian immunodeficiency virus (siv) infection in rhesus macaques parallels many aspects of hiv disease in humans. the purpose of this study was to further characterize the rhesus macaque infected with neurovirulent siv as a model of neuroaids. using a motor skill task, our objective was to detect siv-related movement impairments in behaviorally trained macaques. the motor skill task required retrieval of a food pellet from a cup in a rotating turntable across ...199910475111
the simian immunodeficiency virus envelope glycoprotein contains two epitopes presented by the mamu-a*01 class i molecule.cytotoxic t lymphocyte (ctl) responses against the simian immunodeficiency virus (siv) envelope and gag proteins were monitored in a mamu-a*01-positive rhesus macaque infected with sivsme660. peripheral blood mononuclear cells (pbmc) cultured with synthetic peptides spanning the entire gp160 and gag coding region recognized a total of three epitopes. one located in gag was identified as the previously described mamu-a*01-restricted p11cc-->m epitope (ctpydinqm). the other two epitopes, designate ...199910482552
the human immunodeficiency virus type 1 nef gene can to a large extent replace simian immunodeficiency virus nef in vivo.the nef gene of the pathogenic simian immunodeficiency virus (siv) 239 clone was replaced with primary human immunodeficiency virus type 1 (hiv-1) nef alleles to investigate whether hiv-1 nef can substitute for siv nef in vivo. initially, two rhesus macaques were infected with the chimeric viruses (nef-shivs). most of the nef alleles obtained from both animals predicted intact open reading frames. furthermore, forms containing upstream nucleotide substitutions that enhanced expression of the ins ...199910482588
nodular pneumocystis carinii pneumonia in siv-infected macaques.pneumocystis carinii (pc) pneumonia is a frequent manifestation of the acquired immunodeficiency syndrome (aids) in humans and macaques. an unusual nodular type of pc pneumonia was observed in two simian immunodeficiency virus (siv)-inoculated rhesus macaques (macaca mulatta). these animals developed clinical signs of simian aids, including anorexia, weight loss, dyspnea, and collapse. grossly, both animals had multifocal tan-white nodules 1-10 mm in diameter scattered throughout the lungs. one ...199910490219
induction of b cell hyperplasia in simian immunodeficiency virus-infected rhesus macaques with the simian homologue of kaposi's sarcoma-associated herpesvirus.a simian homologue of kaposi's sarcoma-associated herpesvirus (kshv), the eighth human herpesvirus (hhv8), was isolated from a simian immunodeficiency virus (siv)-infected rhesus macaque (macaca mulatta) that developed a multicentric lymphoproliferative disorder (lpd). this simian rhadinovirus is genetically similar to a recently described rhesus rhadinovirus (rrv) (desrosiers, r.c., v.g. sasseville, s.c. czajak, x. zhang, k.g. mansfield, a. kaur, r.p. johnson, a.a. lackner, and j.u. jung. 1997. ...199910499921
neuropathogenesis of simian immunodeficiency virus in neonatal rhesus macaques.neonatal human immunodeficiency virus (hiv) infection usually occurs intrapartum or postpartum and results in a higher incidence of neurological dysfunction than is seen in adults. to explore the neuropathogenesis of neonatal hiv infection, we infected neonatal macaques with simian immunodeficiency virus (siv) and followed the course of infection focusing on early time points. infected neonates had decreased brain growth and mild histological changes in brain that resembled those seen in pediatr ...199910514404
co-receptor usage of bob/gpr15 in addition to ccr5 has no significant effect on replication of simian immunodeficiency virus in vivo.human immunodeficiency virus type 2 (hiv-2) and the closely related simian immunodeficiency viruses (sivs) frequently use the orphan receptor bob/gpr15 in addition to the chemokine receptor ccr5 for efficient entry and replication. however, the role of bob/gpr15 in replication and pathogenesis of hiv-2 and siv in vivo is unclear. this study shows that a single amino acid substitution in the v3 loop of the pathogenic sivmac239 clone, 321p-->s, impaired the ability to use bob/gpr15 for entry and r ...199910515808
evolution of two types of rhesus lymphocryptovirus similar to type 1 and type 2 epstein-barr virus.rhesus monkeys and other nonhuman old world primates are naturally infected with lymphocryptoviruses (lcv) that are closely related to epstein-barr virus (ebv). a rhesus lcv isolate (208-95) was derived from a b-cell lymphoma in a simian immunodeficiency virus-infected rhesus macaque. the ebna-2 homologues from 208-95 and a previous rhesus lcv isolate (lcl8664) were polymorphic on immunoblotting, so the ebna-2 genes from these two rhesus lcv were cloned, sequenced, and compared. the ebna-2 genes ...199910516028
the effect of one injection of depo-provera on the human vaginal epithelium and cervical ectopy.two studies in rhesus monkeys have shown that progesterone implants, depo-provera and norplant, were associated with vaginal thinning. progesterone implants have also been associated with an increased risk of simian immunodeficiency virus (siv) acquisition. this study in 16 women was done to assess vaginal epithelial thickness and number of cell layers from biopsies taken in the untreated follicular and luteal phases, and at 1 month and 3 months after administration of depo-provera. there was no ...199910549448
transforming growth factor beta is a growth-inhibitory cytokine of b cell lymphoma in siv-infected macaques.cytokine dysregulation is accepted as one of the pivotal factors in the pathogenesis of b cell lymphomas in hiv-positive patients. so far no data exist on inhibitory cytokines in the regulatory network of hiv-associated b-nhl. simian immunodeficiency virus (siv)-infected macaques are a well-established in vivo model of hiv infection in humans. we used this model for the identification of tgf-beta as a growth-inhibitory cytokine of siv-associated b cell lymphomas. fifty-seven rhesus macaques were ...199910555111
performance norms for a rhesus monkey neuropsychological testing battery: acquisition and long-term performance.a computerized behavioral battery based upon human neuropsychological tests (cantab, cenes, cambridge, uk) has been developed to assess cognitive behaviors of rhesus monkeys. monkeys reliably performed multiple tasks, providing long-term assessment of changes in a number of behaviors for a given animal. the overall goal of the test battery is to characterize changes in cognitive behaviors following central nervous system (cns) manipulations. the battery addresses memory (delayed non-matching to ...199910556598
experimental infection of rhesus and pig-tailed macaques with macaque rhadinoviruses.the recognition of naturally occurring rhadinoviruses in macaque monkeys has spurred interest in their use as models for human infection with kaposi sarcoma-associated herpesvirus (human herpesvirus 8). rhesus macaques (macaca mulatta) and pig-tailed macaques (macaca nemestrina) were inoculated intravenously with rhadinovirus isolates derived from these species (rhesus rhadinovirus [rrv] and pig-tailed rhadinovirus [prv]). nine rhadinovirus antibody-negative and two rhadinovirus antibody-positiv ...199910559350
cytotoxic t lymphocytes specific for the simian immunodeficiency virus.a non-human primate model for acquired immunodeficiency syndrome (aids), the simian immunodeficiency virus (siv)-infected rhesus monkey, was used to explore the role of the aids virus-specific cytotoxic t-lymphocyte (ctl) response in disease pathogenesis. this ctl response was measured using the major histocompatibility complex (mhc) class i/peptide tetramer technology. large numbers of tetramer-binding cd8+ t lymphocytes were demonstrable not only in the peripheral blood, but in lymph nodes and ...199910566147
specific passage of simian immunodeficiency virus from end-stage disease results in accelerated progression to aids in rhesus macaques.to determine whether passage of late-stage variants of simian immunodeficiency virus (siv) would lead to a more virulent infection and rapid disease progression, a study was designed to examine the effects of selective transmission of siv from late-stage cases of aids in macaca mulatta. in a uniform group of 10 age-matched animals from the same genetic breeding stock infected with siv(b670), it took 7 months before one of the ten animals developed aids. passage of virus taken from this animal im ...199910567639
survival and failure to thrive in the siv-infected juvenile rhesus monkey.in aids patients, wasting in adults and failure to thrive in children are common and devastating problems. weight loss in rhesus macaques infected with simian immunodeficiency virus (siv) has not been well characterized. the purpose of this study was to determine growth curves in siv-infected juvenile macaques to determine the effects of siv infection on body weight and growth. medical records of seven juvenile male siv-infected macaques were retrospectively reviewed to determine body weights, s ...199910843524
immunohistochemical studies of productive rhesus cytomegalovirus infection in rhesus monkeys (macaca mulatta) infected with simian immunodeficiency virus.in humans infected with the human immunodeficiency virus (hiv), clinical disease due to human cytomegalovirus (hcmv) infection is one of the aids-defining diseases; hcmv is the most common opportunistic infection found postmortem. histologically, the typical lesions are characterized by "owl's eye cells." in rhesus monkeys infected with simian immunodeficiency virus (siv), comparable lesions are caused by an infection with the rhesus cmv (rhcmv). the aim of this study was to investigate the inci ...19999921756
control of viremia in simian immunodeficiency virus infection by cd8+ lymphocytes.clinical evidence suggests that cellular immunity is involved in controlling human immunodeficiency virus-1 (hiv-1) replication. an animal model of acquired immune deficiency syndrome (aids), the simian immunodeficiency virus (siv)-infected rhesus monkey, was used to show that virus replication is not controlled in monkeys depleted of cd8+ lymphocytes during primary siv infection. eliminating cd8+ lymphocytes from monkeys during chronic siv infection resulted in a rapid and marked increase in vi ...19999933172
recombinant simian immunodeficiency virus expressing green fluorescent protein identifies infected cells in rhesus monkeys.we engineered recombinant derivatives of simian immunodeficiency virus (siv) to express enhanced green fluorescent protein (egfp). replacement of vpr sequences with egfp resulted in a genome that did not produce detectable levels of replication-competent virus. replication-competent virus and bright fluorescence of infected cells were obtained with two other constructs, one in which siv nef sequences were replaced by egfp and another in which egfp was inserted into the siv nef locus and hiv-1 ne ...199910024048
effect of complement consumption by cobra venom factor on the the course of primary infection with simian immunodeficiency virus in rhesus monkeys.cobra venom factor (cvf)-induced consumption of complement proteins was used to investigate the role of complement in vivo in the immunopathogenesis of simian immunodeficiency virus of macaques (sivmac) infection in rhesus monkeys. repeated administration of cvf was shown to deplete complement to <5% of baseline hemolytic activity of serum complement for 10 days in a normal monkey. three groups of sivmac-infected animals were then evaluated: monkeys treated with cvf resulting in complement deple ...199910029251
recombinant, attenuated salmonella typhimurium stimulate lymphoproliferative responses to siv capsid antigen in rhesus macaques.recombinant bacteria are useful vectors for delivering foreign antigens to mucosal surfaces and may elicit immune protection against sexually-transmitted pathogens. recombinant, attenuated salmonella typhimurium expressing the simian immunodeficiency virus capsid protein (p27) were given to rhesus macaques by intragastric intubation. this route of immunization was compared with intramuscular injection of soluble p27 in adjuvant, and with immunization protocols that combined intragastric and intr ...199910067699
activation in vivo of retroperitoneal fibromatosis-associated herpesvirus, a simian homologue of human herpesvirus-8.retroperitoneal fibromatosis-associated herpesvirus of rhesus macaques (rfhvmm) is a gammaherpesvirus closely related to human herpesvirus-8 (hhv-8), which is thought to be a necessary cofactor for the development of kaposi's sarcoma (ks) in humans. here, rfhvmm infection of rhesus macaques exposed to the d-type retrovirus simian retrovirus-2 (srv-2) is described. development of srv-2 viraemia, infection with simian immunodeficiency virus or administration of cyclosporin a could result in persis ...199910073709
early short-term 9-[2-(r)-(phosphonomethoxy)propyl]adenine treatment favorably alters the subsequent disease course in simian immunodeficiency virus-infected newborn rhesus macaques.simian immunodeficiency virus (siv) infection of newborn macaques is a useful animal model of human pediatric aids to study disease pathogenesis and to develop intervention strategies aimed at delaying disease. in the present study, we demonstrate that very early events of infection greatly determine the ultimate disease course, as short-term antiviral drug administration during the initial viremia stage significantly delayed the onset of aids. fourteen newborn macaques were inoculated orally wi ...199910074144
comparison of immunity generated by nucleic acid-, mf59-, and iscom-formulated human immunodeficiency virus type 1 vaccines in rhesus macaques: evidence for viral clearance.the kinetics of t-helper immune responses generated in 16 mature outbred rhesus monkeys (macaca mulatta) within a 10-month period by three different human immunodeficiency virus type 1 (hiv-1) vaccine strategies were compared. immune responses to monomeric recombinant gp120sf2 (rgp120) when the protein was expressed in vivo by dna immunization or when it was delivered as a subunit protein vaccine formulated either with the mf59 adjuvant or by incorporation into immune-stimulating complexes (isco ...199910074183
dramatic rise in plasma viremia after cd8(+) t cell depletion in simian immunodeficiency virus-infected macaques.to determine the role of cd8(+) t cells in controlling simian immunodeficiency virus (siv) replication in vivo, we examined the effect of depleting this cell population using an anti-cd8 monoclonal antibody, okt8f. there was on average a 99.9% reduction of cd8 cells in peripheral blood in six infected macaca mulatta treated with okt8f. the apparent cd8 depletion started 1 h after antibody administration, and low cd8 levels were maintained until day 8. an increase in plasma viremia of one to thre ...199910075982
oral transmission of primate lentiviruses.oral transmission of human immunodeficiency virus type 1 (hiv-1) is well documented in children who become infected postnatally through breast milk. in contrast, epidemiologic surveys have yielded conflicting data regarding oral hiv-1 transmission among adults, even though case reports have described seroconversion and the development of aids in adults whose only risk was oral-genital contact. to study oral virus transmission in primate models, we exposed rhesus macaques of various ages to cell- ...199910099108
t cell-tropic simian immunodeficiency virus (siv) and simian-human immunodeficiency viruses are readily transmitted by vaginal inoculation of rhesus macaques, and langerhans' cells of the female genital tract are infected with siv.intravaginal inoculation with t cell-tropic molecular clones of simian immunodeficiency virus (siv) or simian-human immunodeficiency virus (shiv) or some dual-tropic strains of siv or shiv produced systemic infection in rhesus macaques. vaginal inoculation with other dual-tropic molecular clones of siv or shiv did not infect rhesus macaques even after multiple inoculations. while in vitro measures of macrophage tropism do not predict which primate lentiviruses will produce systemic infection aft ...199910099109
mucosal th1- versus th2-type responses for antibody- or cell-mediated immunity to simian immunodeficiency virus in rhesus macaques.simian immunodeficiency virus (siv)-specific b cell responses and the th1- or th2-type profiles of cytokine expression were determined for rhesus macaques immunized with siv antigens via the iliac lymph nodes (by use of a targeted lymph node [tln] procedure) or orally with siv p55gag plus cholera toxin (ct) as a mucosal adjuvant. analysis of cd4+ t cells purified from siv-stimulated peripheral blood mononuclear cells of immunized macaques revealed that th2 cytokine production gradually increased ...199910099124
9-[2-(phosphonomethoxy)propyl]adenine (pmpa) therapy prolongs survival of infant macaques inoculated with simian immunodeficiency virus with reduced susceptibility to pmpa.simian immunodeficiency virus (siv) infection of newborn rhesus macaques is a useful animal model of human immunodeficiency virus infection for the study of the emergence and clinical implications of drug-resistant viral mutants. we previously demonstrated that siv-infected infant macaques receiving prolonged treatment with 9-[2-(phosphonomethoxy)propyl]adenine (pmpa) developed viral mutants with fivefold reduced susceptibility to pmpa in vitro and that the development of these mutants was assoc ...199910103184
effect of 3-hydroxyphthaloyl-beta-lactoglobulin on vaginal transmission of simian immunodeficiency virus in rhesus monkeys.heterosexual transmission of human immunodeficiency virus type 1 (hiv-1) is the major cause of the ongoing aids epidemic. application of chemical barrier methods is expected to contribute to the worldwide control of this epidemic. bovine beta-lactoglobulin modified by 3-hydroxyphthalic anhydride (3-hydroxyphthalovyl-beta-lactoglobulin [3hp-beta-lg]) was shown to inhibit hiv-1, hiv-2, simian immunodeficiency virus (siv), herpes simplex virus type 1 and 2, and chlamydia trachomatis infection in vi ...199910103216
differential tumor necrosis factor alpha production in simian immunodeficiency virus-infected rhesus macaques coinfected with mycobacterium avium.mycobacterium avium infections are the third most common opportunistic infection in patients with aids. simian immunodeficiency virus (siv)-infected rhesus macaques naturally acquire m. avium infections from the environment, and their clinical symptoms are similar to those observed in aids patients. we characterized concurrent infection with siv and m. avium in monkeys on the basis of the growth of the bacteria in macrophages (mphis) from rhesus macaques and the ability of m. avium to induce siv ...199910194069
cd8+ lymphocyte antiviral activity in monkeys immunized with siv recombinant poxvirus vaccines: potential role in vaccine efficacy.protection against intravenous simian immunodeficiency virus (siv) challenge was assessed in rhesus macaques after immunization with a highly attenuated vaccinia (nyvac)-siv recombinant. one-third of vaccinated animals controlled viral infection and progressed to disease more slowly than control animals (benson j, et al.: j virol 1998;72:4170). however, this protection was not associated with neutralizing antibodies, cytotoxic t lymphocytes, or helper t cell responses. to explore other potential ...199910195756
high major histocompatibility complex-unrestricted lysis of simian immunodeficiency virus envelope-expressing cells predisposes macaques to rapid aids progression.before the development of virus-specific immune responses, peripheral blood mononuclear cells (pbmc) from uninfected rhesus monkeys and human beings have the capacity to lyse target cells expressing simian immunodeficiency virus (siv) or human immunodeficiency virus-1 (hiv) envelope (gp130 and gp120) antigens. lysis by naive effector cells does not require major histocompatibility complex (mhc)-restricted antigen presentation, is equally effective for allogeneic and xenogeneic targets, and is de ...199910196261
nef enhances human immunodeficiency virus replication and responsiveness to interleukin-2 in human lymphoid tissue ex vivo.the nef gene is important for the pathogenicity associated with simian immunodeficiency virus infection in rhesus monkeys and with human immunodeficiency virus type 1 (hiv-1) infection in humans. the mechanisms by which nef contributes to pathogenesis in vivo remain unclear. we investigated the contribution of nef to hiv-1 replication in human lymphoid tissue ex vivo by studying infection with parental hiv-1 strain nl4-3 and with a nef mutant (deltanefnl4-3). in human tonsillar histocultures, nl ...199910196292
immunization with a live, attenuated simian immunodeficiency virus vaccine leads to restriction of viral diversity in rhesus macaques not protected from pathogenic challenge.rhesus macaques immunized with simian immunodeficiency virus sivmac239deltanef but not protected from sivmac251 challenge were studied to determine the genetic and biological characteristics of the breakthrough viruses. assessment of siv genetic diversity (env v1-v2) revealed a reduction in the number of viral species in the immunized, unprotected macaques, compared to the number in nonimmunized controls. however, no evidence for selection of a specific v1-v2 genotype was observed, and biologica ...199910196343
type 1 cd4(+) t-cell help is required for induction of antipeptide multispecific cytotoxic t lymphocytes by a lipopeptidic vaccine in rhesus macaques.we have optimized the induction of antiviral cytotoxic t lymphocytes (ctl) in rhesus macaques by a lipopeptide vaccine containing seven peptides from simian immunodeficiency virus (siv) nef and gag proteins and a strong t-helper peptide from tetanus toxoid (tt) that is promiscuous in humans (peptide tt 830-846). two of the eight immunized macaques showed t-helper (th) cell proliferation and a specific synthesis of gamma interferon in response to tt 830-846 peptide. they also showed multispecific ...199910196344
detection of simian immunodeficiency virus gag-specific cd8(+) t lymphocytes in semen of chronically infected rhesus monkeys by cell staining with a tetrameric major histocompatibility complex class i-peptide complex.evaluation of human immunodeficiency virus type 1-specific mucosal cytotoxic t lymphocytes can be hampered by limited cell yields from mucosal sites. we sought to characterize virus-specific cd8(+) t lymphocytes with cytotoxic activity in the male genital tracts of sivmac-infected rhesus monkeys by using a peptide epitope-specific functional t-cell assay and a tetrameric major histocompatibility complex class i-peptide complex. this tetrameric complex was constructed with the rhesus monkey hla-a ...199910196357
gastrointestinal epithelium is an early extrathymic site for increased prevalence of cd34(+) progenitor cells in contrast to the thymus during primary simian immunodeficiency virus infection.the objective of this study was to determine the effects of primary simian immunodeficiency virus (siv) infection on the prevalence and phenotype of progenitor cells present in the gastrointestinal epithelia of siv-infected rhesus macaques, a primate model for human immunodeficiency virus pathogenesis. the gastrointestinal epithelium was residence to progenitor cells expressing cd34 antigen, a subset of which also coexpressed thy-1 and c-kit receptors, suggesting that the cd34(+) population in t ...199910196359
the siv-infected rhesus monkey model for hiv-associated dementia and implications for neurological diseases.the neuropathogenesis of human immunodeficiency virus (hiv)-associated dementia has remained elusive, despite identification of hiv as the causal agent. although a number of contributing factors have been identified, the series of events that culminate in motor and cognitive impairments after hiv infection of the central nervous system (cns) are still not known. rhesus monkeys infected with simian immunodeficiency virus (siv) manifest immunosuppression and cns disease that is pathologically [l. ...199910204575
simian immunodeficiency virus evades a dominant epitope-specific cytotoxic t lymphocyte response through a mutation resulting in the accelerated dissociation of viral peptide and mhc class i.the ability of an aids virus to escape from immune containment by selective mutation away from recognition by ctl was explored in simian immunodeficiency virus of macaques (sivmac)-infected rhesus monkeys. ctl recognition of a previously defined common viral mutation in an immunodominant sivmac gag epitope was evaluated. ctl were assessed for their ability to recognize a sivmac gag protein with a single residue 2 (t --> a) replacement in the minimal epitope peptide bound by the mhc class i molec ...200010843704
the intracytoplasmic domain of the env transmembrane protein is a locus for attenuation of simian immunodeficiency virus sivmac in rhesus macaques.the human and simian immunodeficiency virus (hiv-1 and sivmac) transmembrane proteins contain unusually long intracytoplasmic domains (icd-tm). these domains are suggested to play a role in envelope fusogenicity, interaction with the viral matrix protein during assembly, viral infectivity, binding of intracellular calmodulin, disruption of membranes, and induction of apoptosis. here we describe a novel mutant virus, sivmac-m4, containing multiple mutations in the coding region for the icd-tm of ...200010846063
simian immunodeficiency virus rapidly penetrates the cervicovaginal mucosa after intravaginal inoculation and infects intraepithelial dendritic cells.despite recent insights into mucosal human immunodeficiency virus (hiv) transmission, the route used by primate lentiviruses to traverse the stratified squamous epithelium of mucosal surfaces remains undefined. to determine if dendritic cells (dc) are used by primate lentiviruses to traverse the epithelial barrier of the genital tract, rhesus macaques were intravaginally exposed to cell-free simian immunodeficiency virus sivmac251. we examined formalin-fixed tissues and hla-dr(+)-enriched cell s ...200010846092
the rate of progression to aids is independent of virus dose in simian immunodeficiency virus-infected macaques.of the viral factors that are proposed to influence the rate of progression to aids, the role of infectious dose remains unresolved. intravenous infection of outbred macaca mulatta with various doses of simian immunodeficiency virus isolate 8980 (siv(8980)) revealed an endpoint from which an infectious dose 50 (id(50)) was defined. in the six infected animals, the time to develop aids was variable with a spectrum of rapid, intermediate and slow progressors. high and sustained plasma viraemia wit ...200010859377
direct measurement of cd8+ t cell responses in macaques infected with simian immunodeficiency virus.the simian immunodeficiency virus (siv) macaque model system has been used extensively to study aids pathogenesis and to test candidate vaccines for their ability to protect against homologous or heterologous challenge with pathogenic siv or shiv. recent studies suggest that stimulation of hiv-1-specific ctl responses is important for effective vaccination against hiv-1. while quantitative measurements of siv-specific cytotoxic t lymphocyte (ctl) responses have been facilitated by the use of tet ...200010873778
antiviral treatment normalizes neurophysiological but not movement abnormalities in simian immunodeficiency virus-infected monkeys.simian immunodeficiency virus (siv) infection of rhesus monkeys provides an excellent model of the central nervous system (cns) consequences of hiv infection. to discern the relationship between viral load and abnormalities induced in the cns by the virus, we infected animals with siv and later instituted antiviral treatment to lower peripheral viral load. measurement of sensory-evoked potentials, assessing cns neuronal circuitry, revealed delayed latencies after infection that could be reversed ...200010880046
expression and coreceptor activity of strl33/bonzo on primary peripheral blood lymphocytes.ccr5 and cxcr4 are the major coreceptors that mediate human immunodeficiency virus 1 (hiv-1) infection, while most simian immunodeficiency virus (siv) isolates use ccr5. a number of alternative coreceptors can also mediate infection of some virus strains in vitro, although little is known about their in vivo relevance. therefore, we characterized the expression pattern and coreceptor activity of one of these alternative coreceptors, strl33/bonzo, using a newly developed monoclonal antibody. in a ...200010891428
definition of five new simian immunodeficiency virus cytotoxic t-lymphocyte epitopes and their restricting major histocompatibility complex class i molecules: evidence for an influence on disease progression.simian immunodeficiency virus (siv) infection of the rhesus macaque is currently the best animal model for aids vaccine development. one limitation of this model, however, has been the small number of cytotoxic t-lymphocyte (ctl) epitopes and restricting major histocompatibility complex (mhc) class i molecules available for investigating virus-specific ctl responses. to identify new mhc class i-restricted ctl epitopes, we infected five members of a family of mhc-defined rhesus macaques intraveno ...200010906193
simian immunodeficiency virus (siv) gag dna-vaccinated rhesus monkeys develop secondary cytotoxic t-lymphocyte responses and control viral replication after pathogenic siv infection.the potential contribution of a plasmid dna construct to vaccine-elicited protective immunity was explored in the simian immunodeficiency virus (siv)/macaque model of aids. making use of soluble major histocompatibility class i/peptide tetramers and peptide-specific killing assays to monitor cd8(+) t-lymphocyte responses to a dominant siv gag epitope in genetically selected rhesus monkeys, a codon-optimized siv gag dna vaccine construct was shown to elicit a high-frequency siv-specific cytotoxic ...200010906202
vaccine protection against simian immunodeficiency virus by recombinant strains of herpes simplex virus.an effective vaccine for aids may require development of novel vectors capable of eliciting long-lasting immune responses. here we report the development and use of replication-competent and replication-defective strains of recombinant herpes simplex virus (hsv) that express envelope and nef antigens of simian immunodeficiency virus (siv). the hsv recombinants induced antienvelope antibody responses that persisted at relatively stable levels for months after the last administration. two of seven ...200010933680
differential effects of simian immunodeficiency virus infection on immune inductive and effector sites in the rectal mucosa of rhesus macaques.the rectal mucosa, a region involved in human immunodeficiency virus/simian immunodeficiency virus (siv) infection and transmission, contains immune inductive sites, rectal lymphoid nodules (rln), and effector sites, the lamina propria (lp). this study was designed to evaluate cell populations involved in rectal mucosal immune function in both rln and lp, by immunocytochemical analysis of rectal mucosa from 11 siv-infected (2 to 21 months postinfection) and five naive rhesus macaques. in the rec ...200010934152
inverse correlation of telomerase activity/proliferation of cd4+ t lymphocytes and disease progression in simian immunodeficiency virus-infected nonhuman primates.both increased lymphocyte renewal with subsequent exhaustion of the immune system and impaired t-cell renewal have been put forth to account for cd4+ t-cell depletion and development of aids in hiv-1-infected humans and siv-infected nonhuman primates. in the present study, telomeric terminal restriction fragment length and telomerase activity were used as measures of proliferative activity of t lymphocytes from three nonhuman primate species before and after being infected with siv. in periphera ...200010935683
simian immunodeficiency virus-specific cytotoxic t lymphocytes and cell-associated viral rna levels in distinct lymphoid compartments of sivmac-infected rhesus monkeys.major histocompatibility class i-peptide tetramer technology and simian immunodeficiency virus of macaques (sivmac)-infected rhesus monkeys were used to clarify the distribution of acquired immunodeficiency syndrome virus-specific cytotoxic t lymphocytes (ctl) in secondary lymphoid organs and to assess the relationship between these ctl and the extent of viral replication in the various anatomic compartments. sivmac gag epitope-specific cd8(+) t cells were evaluated in the spleen, bone marrow, t ...200010942394
homozygosity for a conserved mhc class ii dq-drb haplotype is associated with rapid disease progression in simian immunodeficiency virus-infected macaques: results from a prospective study.in human immunodeficiency virus type 1 (hiv-1)-infected individuals, disease progression varies considerably. this is also observed after experimental infection of macaques with simian immunodeficiency virus (siv). major histocompatibility complex (mhc) genes may influence disease progression in both species. homozygosity for mhc-mamu (macaca mulatta)-dqb1*0601 was previously identified to be associated with rapid disease progression in siv-infected macaques. to validate the association of this ...200010950764
differential dynamics of cd4(+) and cd8(+) t-lymphocyte proliferation and activation in acute simian immunodeficiency virus infection.although lymphocyte turnover in chronic human immunodeficiency virus and simian immunodeficiency virus (siv) infection has been extensively studied, there is little information on turnover in acute infection. we carried out a prospective kinetic analysis of lymphocyte proliferation in 13 rhesus macaques inoculated with pathogenic siv. a short-lived dramatic increase in circulating ki-67(+) lymphocytes observed at 1 to 4 weeks was temporally related to the onset of siv replication. a 5- to 10-fol ...200010954541
induction of mucosal homing virus-specific cd8(+) t lymphocytes by attenuated simian immunodeficiency virus.induction of virus-specific t-cell responses in mucosal as well as systemic compartments of the immune system is likely to be a critical feature of an effective aids vaccine. we investigated whether virus-specific cd8(+) lymphocytes induced in rhesus macaques by immunization with attenuated simian immunodeficiency virus (siv), an approach that is highly effective in eliciting protection against mucosal challenge, express the mucosa-homing receptor alpha4beta7 and traffic to the intestinal mucosa ...200010954580
simian-human immunodeficiency virus-associated nephropathy in macaques.a number of chimeric simian-human immunodeficiency virus (shiv) viruses containing tat, rev, vpu, and env from hiv-1 (strain hxbc2) in a genetic background of simian immunodeficiency virus (siv(mac)239) have been derived from the parental nonpathogenic shiv-4 virus. in this article we examine the renal pathology associated with the derivation of these pathogenic shiv strains. the first of the pathogenic shivs, shiv(ku-1), is associated with rapid cd4(+) t cell loss and opportunistic infections a ...200010957726
progressive multifocal leukoencephalopathy and oligodendroglioma in a monkey co-infected by simian immunodeficiency virus and simian virus 40.a rhesus monkey experimentally inoculated with simian immunodeficiency virus (siv) mac251 was killed 42 months later because of poor general condition. cd4 lymphocyte count which was 3,430/mm3 before inoculation, had decreased to 638/mm3 2 months before death. neuropathological examination revealed changes characteristic of progressive multifocal leukoencephalopathy (pml) in the white matter of the cerebral hemispheres and brain stem. in situ hybridization was negative for jc virus but markedly ...200010965804
the chimpanzee and other non-human-primate models in hiv-1 vaccine research.animal models are of great importance for the study of disease pathogenesis, particularly non-human-primate models of infectious diseases. the role of non-human primates in hiv-1 research is continually discussed and debated. here, we examine three primate models: chimpanzee-hiv-1, rhesus macaque-simian immunodeficiency virus and rhesus macaque-shiv, and discuss immunological similarities and differences, safety and monetary issues, and ethical concerns.200010989311
the replicative capacity of rhesus macaque peripheral blood mononuclear cells for simian immunodeficiency virus in vitro is predictive of the rate of progression to aids in vivo.survival of rhesus macaques (macaca mulatta) experimentally infected with simian immunodeficiency virus (siv) varies significantly from animal to animal. some animals die within 2 months while others survive for more than 5 years, even when identical inocula are used. this diversity in survival creates a significant problem in the design of therapeutic and vaccine trials using the siv-macaque model because the use of small numbers of animals may provide results that are misleading. identifying a ...200010993932
intrinsic susceptibility of rhesus macaque peripheral cd4(+) t cells to simian immunodeficiency virus in vitro is predictive of in vivo viral replication.previous studies with simian immunodeficiency virus (siv) infection of rhesus macaques suggested that the intrinsic susceptibility of peripheral blood mononuclear cells (pbmc) to infection with siv in vitro was predictive of relative viremia after siv challenge. the present study was conducted to evaluate this parameter in a well-characterized cohort of six rhesus macaques selected for marked differences in susceptibility to siv infection in vitro. rank order relative susceptibility of pbmc to s ...200011000207
preparation and induction of immune responses by a dna aids vaccine.in an effort to evaluate the feasibility of developing a safe dna vaccine for acquired immunodeficiency syndrome (aids), we have prepared a plasmid-based immunogen modeled after a naturally occurring noninfectious mutant of the simian immunodeficiency virus (siv). the mutant siv genome produces defective virus particles that are noninfectious in vitro and nonpathogenic in vivo in rhesus macaques. analysis of the mutant genome revealed a 1.6 kb deletion that is in frame and spans integrase, vif, ...200011016598
viremia control following antiretroviral treatment and therapeutic immunization during primary siv251 infection of macaques.prolonged antiretroviral therapy (art) is not likely to eradicate human immunodeficiency virus type i (hiv-i) infection. here we explore the effect of therapeutic immunization in the context of art during primary infection using the simian immunodeficiency virus (siv251) macaque model. vaccination of rhesus macaques with the highly attenuated poxvirus-based nyvac-siv vaccine expressing structural genes elicited vigorous virus-specific cd4 + and cd8+ t cell responses in macaques that responded ef ...200011017146
disrupting surfaces of nef required for downregulation of cd4 and for enhancement of virion infectivity attenuates simian immunodeficiency virus replication in vivo.the multifunctional simian and human immunodeficiency virus (siv and hiv) nef proteins are important for virulence. we studied the importance of selected nef functions using an siv nef with mutations in two regions that are required for cd4 downregulation. this nef mutant is defective for downregulating cd4 and, in addition, for enhancing siv infectivity and induction of siv replication from infected quiescent peripheral blood mononuclear cells, but not for other known functions, including downr ...200011024110
enterocytozoon bieneusi as a cause of proliferative serositis in simian immunodeficiency virus-infected immunodeficient macaques (macaca mulatta).enterocytozoon bieneusi is the most frequent microsporidian parasite of human patients with acquired immunodeficiency syndrome and is a significant cause of diarrhea and wasting. recently, this organism has also been recognized as a spontaneous infection of several species of captive macaques. as in humans, e bieneusi frequently causes enteropathy and cholangiohepatitis in immunodeficient simian immunodeficiency virus (siv)-infected macaques.200011035580
effect of a cellulose acetate phthalate topical cream on vaginal transmission of simian immunodeficiency virus in rhesus monkeys.human immunodeficiency virus type 1 (hiv-1) infection continues to spread in developing countries, mostly through heterosexual transmission. the development of a safe and cost-effective topical microbicide, effective against a range of stds including hiv-1, would greatly impact the ongoing epidemic. when formulated in a vehicle, a micronized form of cellulose acetate phthalate (cap), which is an inactive pharmaceutical excipient, has been shown to inactivate hiv-1, herpes simplex virus types 1 a ...200011036053
b-cell leukemia in a rhesus macaque (macaca mulatta) infected with simian immunodeficiency virus.conditions associated with abnormal b-cell proliferation have an increased incidence in the hiv-infected population. a longitudinal study conducted at the tulane regional primate research center has followed more than 1,000 rhesus macaques infected with simian-immunodeficiency virus (siv) since 1984. while spontaneous b-cell malignancy in siv-negative macaques has not been reported, 42 cases of siv-associated-lymphoma (sal) have been documented in this cohort. recently we identified a single cas ...200011042530
mechanisms for adaptation of simian immunodeficiency virus to replication in alveolar macrophages.in contrast to the simian immunodeficiency virus sivmac239, which replicates poorly in rhesus monkey alveolar macrophages, a variant with nine amino acid changes in envelope (sivmac239/316e) replicates efficiently and to high titer in these same cells. we examined levels of viral dna, rna, antigen, and infectious virus to identify the nature of the block to sivmac239 replication in these cells. low levels of viral antigen (0.1 to 1.0 ng of p27 per ml) and infectious virus (100 to 1,000 infectiou ...200011044136
pulmonary cryptosporidiosis in simian immunodeficiency virus-infected rhesus macaques.cryptosporidiosis is a common opportunistic infection in the gastrointestinal tract of human and nonhuman primates with aids. pulmonary infection associated with cryptosporidium spp. has not been previously reported in monkeys. two macaques experimentally infected with simian immunodeficiency virus (siv) had lesions containing cryptosporidial organisms involving the trachea, lungs, bile ducts, pancreas, and intestine. the pulmonary sections revealed moderate to severe bronchopneumonia associated ...200011055873
the level of cd4 expression limits infection of primary rhesus monkey macrophages by a t-tropic simian immunodeficiency virus and macrophagetropic human immunodeficiency viruses.the entry of primate immunodeficiency viruses into cells is dependent on the interaction of the viral envelope glycoproteins with receptors, cd4, and specific members of the chemokine receptor family. although in many cases the tropism of these viruses is explained by the qualitative pattern of coreceptor expression, several instances have been observed where the expression of a coreceptor on the cell surface is not sufficient to allow infection by a virus that successfully utilizes the corecept ...200011069993
early changes in peripheral blood t cells during primary infection of rhesus macaques with a pathogenic siv.primary infection of rhesus macaques with pathogenic strains of simian immunodeficiency virus (siv) leads to rapid and dynamic changes in both viral load and t cell counts in the peripheral blood. we have performed a sequential analysis of peripheral blood cd4 and cd8 t cells in five macaques during the 8 weeks following sivmac251 infection. we observed a transient lymphopenia of both cd4 and cd8 t cells during the first 2 weeks, followed by a rebound. the primary phase of infection was associat ...200011085574
long-term follow-up study on siv intestinal proviral load in rhesus macaques.after experimental infection with simian immunodeficiency virus (siv), intestinal endoscopy proved to be an easily tolerated, minimal invasive procedure to obtain biopsies from the gastrointestinal tract of rhesus macaques during all stages of disease. as the gi tract is affected by many opportunistic infections and immunological impairment after siv/human immunodeficiency virus (hiv) infection, knowledge on the proviral load is an important parameter for a better understanding of disease pathog ...200011085575
identification of siv env-specific ctl in the jejunal mucosa in vaginally exposed, seronegative rhesus macaques (macaca mulatta).we previously reported major histocompatibility complex class i-restricted cytotoxic t lymphocytes (ctl) in jejunal lamina propria (lp) of monkeys following colonic exposure to subinfectious siv doses. those monkeys with strong mucosal ctl responses specific for simian immunodeficiency virus (siv) envelope (env) were protected from later colonic challenge with a heterologous pathogenic virus dose. here, env-specific ctl were similarly induced in jejunal lp in five of eight non-progesterone treat ...200011085580
interactions between mycobacterium leprae and simian immunodeficiency virus (siv) in rhesus monkeys.groups of rhesus monkeys were inoculated with: 1) simian immunodeficiency virus (siv)b670 alone; 2) mycobacterium leprae alone; 3) siv plus m. leprae on the same day; and 4) m. leprae 2 weeks after siv. animals were monitored at intervals for virus loads, antibody responses to m. leprae glycolipid antigens and to siv gp120, t-cell cd4+ and cd4+ cd29+ subset percentages, leprosy and acquired immunodeficiency syndrome (aids) clinical symptoms. five out of six animals developed leprosy in each co-i ...200011085588
effect of mycobacterial infection on virus loads and disease progression in simian immunodeficiency virus-infected rhesus monkeys.the effect of a mycobacterial infection on aids disease was studied in the simian model. monkeys were infected with the primary virulent isolate siv/deltab670 and inoculated 90 days later with bcg, an attenuated strain of mycobacterium bovis. all monkeys experienced a dramatic transient increase in plasma viremia and ccr5 expression on t lymphocytes after bcg inoculation. only two of the four siv+ animals had substantial proliferative responses to ppd, with poor responders developing disseminate ...200011118075
temporal loss of nef-epitope ctl recognition following macaque lipopeptide immunization and siv challenge.to address the subtle interactions between antiviral cytotoxic t-cell (ctl) immune responses and the evolution of viral quasispecies variants in vivo, we performed a longitudinal study in a simian immunodeficiency virus (siv)-infected rhesus macaque that had a long experimental siv infection before developing simian aids. before being infected with siv, this animal was immunized with a mixture of seven lipopeptides derived from siv nef and gag proteins and showed a bispecific antiviral ctl respo ...200011118377
vaccination of macaques against pathogenic simian immunodeficiency virus with venezuelan equine encephalitis virus replicon particles.vaccine vectors derived from venezuelan equine encephalitis virus (vee) that expressed simian immunodeficiency virus (siv) immunogens were tested in rhesus macaques as part of the effort to design a safe and effective vaccine for human immunodeficiency virus. immunization with vee replicon particles induced both humoral and cellular immune responses. four of four vaccinated animals were protected against disease for at least 16 months following intravenous challenge with a pathogenic siv swarm, ...200010590126
the kinetics of specific immune responses in rhesus monkeys inoculated with live recombinant bcg expressing siv gag, pol, env, and nef proteins.development of an effective preventive or therapeutic vaccine against hiv-1 is an important goal in the fight against aids. effective virus clearance and inhibition of spread to target organs depends principally on the cellular immune response. therefore, a vaccine against hiv-1 should elicit virus-specific cytotoxic lymphocyte (ctl) responses to eliminate the virus during the cell-associated stages of its life cycle. the vaccine should also be capable of inducing immunity at the mucosal surface ...200010683331
immunization with a modified vaccinia virus expressing simian immunodeficiency virus (siv) gag-pol primes for an anamnestic gag-specific cytotoxic t-lymphocyte response and is associated with reduction of viremia after siv challenge.the immunogenicity and protective efficacy of a modified vaccinia virus ankara (mva) recombinant expressing the simian immunodeficiency virus (siv) gag-pol proteins (mva-gag-pol) was explored in rhesus monkeys expressing the major histocompatibility complex (mhc) class i allele, mamua*01. macaques received four sequential intramuscular immunizations with the mva-gag-pol recombinant virus or nonrecombinant mva as a control. gag-specific cytotoxic t-lymphocyte (ctl) responses were detected in all ...200010684264
containment of simian immunodeficiency virus infection: cellular immune responses and protection from rechallenge following transient postinoculation antiretroviral treatment.to better understand the viral and host factors involved in the establishment of persistent productive infection by primate lentiviruses, we varied the time of initiation and duration of postinoculation antiretroviral treatment with tenofovir (9-[2-(r)-(phosphonomethoxy)propyl]adenine) while performing intensive virologic and immunologic monitoring in rhesus macaques, inoculated intravenously with simian immunodeficiency virus sivsme660. postinoculation treatment did not block the initial infect ...200010684272
recombinant modified vaccinia virus ankara expressing the surface gp120 of simian immunodeficiency virus (siv) primes for a rapid neutralizing antibody response to siv infection in macaques.neutralizing antibodies were assessed before and after intravenous challenge with pathogenic sivsme660 in rhesus macaques that had been immunized with recombinant modified vaccinia virus ankara expressing one or more simian immunodeficiency virus gene products (mva-siv). animals received either mva-gag-pol, mva-env, mva-gag-pol-env, or nonrecombinant mva. although no animals were completely protected from infection with siv, animals immunized with recombinant mva-siv vaccines had lower virus loa ...200010684319
the t-cell receptor zeta chain contains two homologous domains with which simian immunodeficiency virus nef interacts and mediates down-modulation.we have recently demonstrated that simian immunodeficiency virus (siv) nef binds to the zeta chain of the t-cell receptor (tcr), leading to its down-modulation from t-cell surfaces (i. bell, c. ashman, j. maughan, e. hooker, f. cook, and t. a. reinhart, j. gen. virol. 79:2717-2727, 1998). using a panel of human as well as rhesus macaque tcr zeta cytoplasmic domain mutants, we have identified in this report two linear peptides in the cytoplasmic domain of tcr zeta which independently interact wit ...200010708444
modulation of antigen-specific humoral responses in rhesus macaques by using cytokine cdnas as dna vaccine adjuvants.an important limitation of dna immunization in nonhuman primates is the difficulty in generating high levels of antigen-specific antibody responses; strategies to enhance the level of immune responses to dna immunization may be important in the further development of this vaccine strategy for humans. we approached this issue by testing the ability of molecular adjuvants to enhance the levels of immune responses generated by multicomponent dna vaccines in rhesus macaques. rhesus macaques were coi ...200010708463
opioids suppress chemokine-mediated migration of monkey neutrophils and monocytes - an instant response.opioid users having acquired human immunodeficiency syndrome (aids) are at a greater risk than non-users of contracting opportunistic infections. opioid-administered and simian immunodeficiency virus (siv)-infected rhesus monkeys have been an excellent model for studying aids and drug abuse in humans. in this study, chemotaxis of monkey leukocytes was evaluated using the chemokines interleukin-8 (il-8) and regulated upon activation, normal t cell expressed (rantes) as the chemoattractants, and t ...200010708810
quantitative image analysis of simian immunodeficiency virus replication in macrophages coinfected with mycobacterium avium complex.mycobacterium avium is the most frequent cause of disseminated bacterial infection in patients with human immunodeficiency virus type 1 infection and in rhesus macaques with simian immunodeficiency virus (siv) infection. this animal model of aids was used to test the hypothesis that this frequent association is the result of reciprocal enhancement of replication of both microorganisms. the replication of m. avium and siv was analyzed in lymphatic tissues obtained from rhesus macaques experimenta ...200010720506
in vitro ethanol suppresses alveolar macrophage tnf-alpha during simian immunodeficiency virus infection.pulmonary infections are a significant cause of morbidity and mortality in patients with alcohol abuse and human immunodeficiency virus (hiv) infection, two immunocompromising conditions that frequently coexist. this study examined the separate and combined effects of in vivo lentiviral infection and in vitro alcohol exposure on alveolar macrophage (am) production of tumor necrosis factor- alpha (tnf-alpha), a proinflammatory cytokine that is critical to normal pulmonary host defense. ams, recov ...200010619810
normal t-cell turnover in sooty mangabeys harboring active simian immunodeficiency virus infection.sooty mangabeys naturally infected with simian immunodeficiency virus (siv) remain healthy though they harbor viral loads comparable to those in rhesus macaques that progress to aids. to assess the immunologic basis of disease resistance in mangabeys, we compared the effect of siv infection on t-cell regeneration in both monkey species. measurement of the proliferation marker ki-67 by flow cytometry showed that mangabeys harbored proliferating t cells at a level of 3 to 4% in peripheral blood ir ...200010627531
dilated cardiomyopathy associated with simian aids in nonhuman primates.cardiomyopathy is being recognized with increasing frequency in patients with aids, yet the relationship between hiv infection and cardiac contractile dysfunction remains obscure. the purpose of the present study was to determine if infection with simian immunodeficiency virus (siv) in nonhuman primates is associated with cardiac dysfunction and myocardial injury.200010637207
a strategy for cloning infectious molecular clones of retroviruses from serum or plasma.to enable biological characterisation of lentiviral variants which emerge during infection and development of aids, a method was developed to construct molecular clones from circulating simian immunodeficiency virus (siv) particles present in as little as 20 microl of serum from infected rhesus monkeys. this technique uses a long distance rt-pcr method optimised for the amplification of partly overlapping 5-kb siv (half genome) amplimers. ligation of the genome halves resulted in the constructio ...200010644085
cytokine expression, natural killer cell activation, and phenotypic changes in lymphoid cells from rhesus macaques during acute infection with pathogenic simian immunodeficiency virus.we studied the innate and adaptive immune system of rhesus macaques infected with the virulent simian immunodeficiency virus isolate sivmac251 by evaluating natural killer (nk) cell activity, cytokine levels in plasma, humoral and virological parameters, and changes in the activation markers cd25 (interleukin 2r ¿il-2r alpha chain), cd69 (early activation marker), and cd154 (cd40 ligand) in lymphoid cells. we found that infection with sivmac251 induced the sequential production of interferon-alp ...200010644334
antiretroviral therapy during primary immunodeficiency virus infection can induce persistent suppression of virus load and protection from heterologous challenge in rhesus macaques.a limited period of chemotherapy during primary immunodeficiency virus infection might provide a long-term clinical benefit even if treatment is initiated at a time point when virus is already detectable in plasma. to evaluate this strategy, we infected rhesus macaques with the pathogenic simian/human immunodeficiency virus rt-shiv and treated them with the antiretroviral drug (r)-9-(2-phosphonylmethoxypropyl)adenine (pmpa) for 8 weeks starting 7 or 14 days postinfection. pmpa treatment suppress ...200010644340
pathogenic conversion of live attenuated simian immunodeficiency virus vaccines is associated with expression of truncated nef.rhesus macaques infected with simian immunodeficiency virus (siv) containing either a large nef deletion (sivmac239delta(152)nef) or interleukin-2 in place of nef developed high virus loads and progressed to simian aids. viruses recovered from both juvenile and neonatal macaques with disease produced a novel truncated nef protein, tnef. viruses recovered from juvenile macaques infected with serially passaged virus expressing tnef exhibited a pathogenic phenotype. these findings demonstrated stro ...200010644378
rhesus lymphocryptovirus infection during the progression of saids and saids-associated lymphoma in the rhesus macaque.saids-associated lymphoma (sal) represents a monoclonal expansion of b-cell origin in which simian immunodeficiency virus (siv) infection is not detected. however, tumor cells are frequently infected with rhesus lymphocryptovirus (rhlcv), a rhesus homologue of epstein-barr virus (ebv). in previous studies, the incidence of rhlcv infection in sal was determined to be 89% as measured by polymerase chain reaction (pcr) and/or in situ hybridization. the main objective of the present study was to asc ...200010659055
simian immunodeficiency virus-specific cytotoxic t lymphocytes and protection against challenge in rhesus macaques immunized with a live attenuated simian immunodeficiency virus vaccine.in this study, we examined the role of simian immunodeficiency virus (siv)-specific cytotoxic t lymphocytes (ctls) in macaques immunized with an attenuated strain of simian immunodeficiency virus (sivmac239deltanef) in protection against pathogenic challenge with sivmac251. our results indicate that attenuated sivmac239deltanef can elicit specific ctl precursor cells (ctlp), but no correlation was observed between breadth or strength of ctlp response to structural proteins siv-env, -gamg or -pol ...200010612675
simian immunodeficiency virus containing mutations in n-terminal tyrosine residues and in the pxxp motif in nef replicates efficiently in rhesus macaques.sivmac nef contains two n-terminal tyrosines that were proposed to be part of an sh2-ligand domain and/or a tyrosine-based endocytosis signal and a putative sh3-ligand domain (p(104)xxp(107)). in the present study, we investigated the effects of combined mutations in these tyrosine and proline residues on simian immunodeficiency virus (siv) nef interactions with the cellular signal transduction and endocytic machinery. we found that mutation of y(28)f, y(39)f, p(104)a, and p(107)a (ffaa-nef) had ...200010756028
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