Publications

vaccine effect using a live attenuated nef-deficient simian immunodeficiency virus of african green monkeys in the absence of detectable vaccine virus replication in vivo.	immunization of adult macaques with live attenuated simian immunodeficiency viruses (sivs) lacking the nef genes has been shown to protect against challenge with full-length pathogenic siv. to test live attenuated virus vaccines for the first time in a natural host we have constructed a mutant siv from african green monkeys (sivagm) with a deletion of 125 bp in the nef gene (sivagm3 delta nef). this mutant showed moderately delayed in vitro replication in the t cell line molt-4/8 and in primary ...	1997	9108105
loss of the sivsmmpbj14 phenotype and nef genotype during long-term survival of macaques infected by mucosal routes.	the ability of the simian immunodeficiency virus sivsmmpbj14 (siv-pbj14) to activate and induce proliferation of quiescent peripheral blood lymphocytes from macaques is an in vitro correlate of its acutely lethal in vivo phenotype. siv-pbj14 differs from other siv strains by encoding tyrosine at amino acid 17 (y17) in nef, which generates an activation motif important for signal transduction. although intravenous inoculation of pig-tailed macaques with siv-pbj14 uniformly leads to death within 2 ...	1997	9126264
isolation of sooty mangabey simian t-cell leukemia virus type i [stlv-i(sm)] and characterization of a mangabey t-cell line coinfected with stlv-i(sm) and simian immunodeficiency virus sivsmmpbj14.	it has been postulated that dual infections of humans with human immunodeficiency virus (hiv) and human t-cell leukemia/lymphotropic virus (htlv) may potentiate disease progression. counterparts of both of these pathogenic human retroviruses have been identified in various simian species indigenous to asia and africa, including sooty mangabey monkeys (cercocebus atys). using peripheral blood mononuclear cells (pbmc) from a mangabey naturally infected with both siv and stlv-i, t-cell lines were e ...	1997	9281507
the cytopathicity of a simian immunodeficiency virus mne variant is determined by mutations in gag and env.	previous studies suggested that the rapidly replicating, highly cytopathic, syncytium-inducing (rapid-high/si) phenotype of simian immunodeficiency virus mne variants that evolved in macaques inoculated with a slowly replicating, minimally cytopathic, non-syncytium-inducing (slow-low/nsi) molecular clone was not solely the result of changes in the envelope surface protein (env su). to define the viral determinants responsible for the change in phenotype, we molecularly cloned a rapid-high/si var ...	1997	9311845
specific n-linked and o-linked glycosylation modifications in the envelope v1 domain of simian immunodeficiency virus variants that evolve in the host alter recognition by neutralizing antibodies.	during progression to aids in simian immunodeficiency virus (siv) mne-infected macaques, viral variants are selected that encode sequences with serine and threonine changes in variable region 1 (v1) of the surface component of the viral envelope protein (env-su). because these serine and threonine amino acid changes are characteristic of sites for o-linked and n-linked glycosylation, we examined whether they were targets for modification by carbohydrates. for this purpose, we used several bioche ...	1997	9311856
infection of macaca nemestrina neonates with hiv-1 via different routes of inoculation.	receptive anal intercourse but not orogenital sex has been identified as a major risk factor for transmission of hiv-1. recent studies using simian immunodeficiency virus (siv) in rhesus macaques have demonstrated relatively efficient infection following oral administration, indicating that modes of transmission may vary between hiv-1 and siv. here, we investigate whether hiv-1 infection of macaques via the oral route is more efficient than via the rectal route.	1997	9365759
a malignant astrocytoma containing simian virus 40 dna in a macaque infected with simian immunodeficiency virus.	polyomaviruses have proven oncogenicity in nonhost experimental animals; however, studies concerning the association between human brain tumors and simian and human polyomaviruses have yielded inconclusive results. we examined the relationship of sv40 to a malignant astrocytoma found in the right frontal lobe of a pigtail macaque (macaca nemestrina) infected with simian immunodeficiency virus (siv). consistent with the histologic diagnosis, the tumor was immunoreactive with antibodies to s-100 p ...	1997	9379484
protection against lethal simian immunodeficiency virus sivsmmpbj14 disease by a recombinant semliki forest virus gp160 vaccine and by a gp120 subunit vaccine.	infection of pigtail macaques with sivsmmpbj14, biological clone 3 (siv-pbj14-bc13), produces an acute and usually fatal shock-like syndrome 7 to 14 days after infection. we used this simian immunodeficiency virus (siv) model as a rapid and rigorous challenge to evaluate the efficacy of two siv env vaccine strategies. groups of four pigtail macaques were immunized four times over a 25-week span with either a recombinant semliki forest virus expressing the siv-pbj14 env gp160 (sfv-sivgp160) or pu ...	1996	8627721
chimeric simian/human immunodeficiency virus that causes progressive loss of cd4+ t cells and aids in pig-tailed macaques.	by animal-to-animal passage of simian/human immunodeficiency virus (shiv) in pig-tailed macaques, we have developed a macaque model of human immunodeficiency virus type 1 (hiv-1) disease in humans. passaging was begun with a chimeric virus containing the env gene of hiv-1 hxbc2 and the gag and pol genes of simian immunodeficiency virus sivmac239. shiv was passaged serially in cohorts of two macaques each, using bone marrow-to-bone marrow transfers at 5, 5, and 16 weeks for passages 2, 3, and 4, ...	1996	8627799
requirements for lymphocyte activation by unusual strains of simian immunodeficiency virus.	when residues 17 and 18 in nef of simian immunodeficiency virus strain sivmac239 were changed from rq to ye, the resultant virus was able to replicate in peripheral blood mononuclear cell cultures without prior lymphocyte activation and without the addition of exogenous interleukin-2, caused extensive lymphocyte activation in these cultures, and produced an acute disease in rhesus and pigtail macaques (z. du, s. m. lang, v. g. sasseville, a. a. lackner, p. 0. ilyinskii, m. d. daniel, j. u. jung, ...	1996	8648760
deletion of the nef gene abrogates the ability of siv smmpbj to induce acutely lethal disease in pigtail macaques.	simian immunodeficiency virus (siv) infection in macaque species is typically associated with the development of a progressive immunodeficiency disease, similar to human aids, resulting in death of animals in months to years after infection. in contrast, a variant virus, termed sivsmmpbj, induces an acute disease in macaques, resulting in death in 5 to 14 days after infection. previously, we have shown that several viral determinants contribute to the pathogenesis of this disease. the present st ...	1996	8744583
a case of pulmonary cestodiasis in a simian immunodeficiency virus-infected pigtailed macaque (macaca nemestrina) in which virus-infected leukocytes are present within the lesion.	the larvae of mesocestoides are rarely encountered in nonhuman primates, with most cases reported in baboons. infection of macaques has been occasionally diagnosed, but mesocestoides in the lung parenchyma is extremely rare. we have previously demonstrated that in macaques with terminal aids, simian immunodeficiency virus (siv)-infected leukocytes are rarely found in cellular infiltrates associated with opportunistic infections or preexisting disease. here we describe larvae (tetrathyridia) of t ...	1996	8906603
nucleotide sequence of the hiv-2 eho genome, a divergent hiv-2 isolate.	the hiv-2 eho isolate from cote d'ivoire has been characterized as a highly cytopathic hiv-2 strain, which can be differentiated from other isolates by the smaller size of its external envelope glycoprotein. the entire nucleotide sequence (10,352 bp) of the hiv-2 eho genome is filed in the embl/genbank data libraries under accession no. u27200. despite its high degree of variability, the genetic organization of hiv-2 eho was found to be similar to other hiv-2 and simian immunodeficiency virus ...	1995	7546916
phylogeny and natural history of the primate lentiviruses, siv and hiv.	studies of primate lentivirus phylogeny over the past decade have established a minimum of five related, but genetically distinct, groups of simian immunodeficiency virus (siv), each originating from a different african primate species. the hypothesis that hiv-2 (and sivmac) arose by cross-species transmission from sooty mangabeys (cercocebus atys has been strengthened by a more detailed characterization of the sivsm/sivmac/hiv-2 group of viruses. siv from all four subspecies of african green mo ...	1995	8745080
receptor function of cd4 structures from african green monkey and pig-tail macaque for simian immunodeficiency virus, sivsm, sivagm, and human immunodeficiency virus type-1.	differences in kinetics of infection, cellular tropism, and cytopathology of siv and hiv appear to depend on both viral and host factors. we investigated the role of critical cd4 structures from african green monkeys (agm) a natural siv host, from pig-tailed macaques (pt) an unnatural siv host, and from humans, as well as the role of species-specific cellular factors involved in the tropism, kinetics of infection, and cytopathic effects of several siv and hiv-1. critical regions of the pt macaqu ...	1995	8833265
[progress in vaccination against aids].	two vaccination trials against aids viruses are reported. the first trial was a prophylactic vaccination carried out in the pig-tailed macaque (macacca nemestrina) against simian immunodeficiency virus (siv) variant pbj14. the immunogen was a semliki forest virus (sfv) recombinant expressing sfv - pbj14 envelope protein. vaccination did not prevent infection but protected the animals against the disease (a fulminant form of aids that kills the animal within 12-15 days). the second trial was a th ...	1995	8845793
the u3 promoter region of the acutely lethal simian immunodeficiency virus clone smmpbj1.9 confers related biological activity on the apathogenic clone agm3mc.	infection with the acutely pathogenic molecular virus clone sivsmmpbj1.9, cloned from isolate pbj14 of simian immunodeficiency virus (siv) from sooty mangabey monkeys (cercocebus atys), leads to acute viral and often lethal disease within days or weeks. sivsmmpbj1.9 has the unique property of replicating in nonstimulated peripheral blood mononuclear cells from pig-tailed macaques. in contrast, molecular virus clone sivagm3mc of siv from african green monkeys (cercopithecus aethiops), which is ap ...	1995	7877983
molecular and biological analyses of quasispecies during evolution of a virulent simian immunodeficiency virus, sivsmmpbj14.	a prototypic simian immunodeficiency virus (sivsmm9), isolated from a naturally infected sooty mangabey (cercocebus atys), was passaged in vivo in a pig-tailed macaque (macaca nemestrina) having the identifier pbj. when pbj died of a typical aids-like syndrome 14 months after infection, the virus isolated from its tissues was subsequently shown to differ from sivsmm9 genetically and biologically. most notably, this isolate, sivsmmpbj14 (siv-pbj14), is the most virulent primate lentivirus known: ...	1995	7884848
an acutely lethal simian immunodeficiency virus stimulates expansion of v beta 7- and v beta 14-expressing t lymphocytes.	sivsmmpbj14, a variant simian immunodeficiency virus isolated from a pig-tailed macaque, stimulates the proliferation of macaque t lymphocytes in vitro and induces an acutely lethal disease in macaques characterized, in part, by lymphadenopathy and splenomegaly. to determine whether sivsmmpbj14 exhibits superantigen-like activity, in vitro and in vivo studies of t-cell receptor v beta repertoire were undertaken using pcr-based quantitative methods. whereas in vitro phytohemagglutinin stimulation ...	1994	7914369
viral genetic determinants in sivsmmpbj pathogenesis.	a variant simian immunodeficiency virus (siv) from sooty mangabeys, sivsmmpbj, induces an acutely lethal disease in pigtailed macaques (macaca nemestrina). this study further characterizes the viral genetic determinants involved in this acutely lethal disease. we have generated chimeric molecular clones constructed between sivsmmpbj and either sivsmh4 or sivsmm9 to analyze the role of the 5' half of the genome and the envelope gene in the induction of acute disease. these studies suggest that th ...	1994	7966228
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.	1994	7966238
immune activation and viral burden in acute disease induced by simian immunodeficiency virus sivsmmpbj14: correlation between in vitro and in vivo events.	the simian immunodeficiency virus sivsmmpbj14 (siv-pbj14) is an atypical lentivirus that causes acute disease and death in pig-tailed macaques and in vitro replicates efficiently in resting macaque lymphocytes and activates and induces proliferation of lymphocytes. the present study was conducted to test the hypothesis that production of large quantities of siv-pbj14 induces widespread immune activation and elaboration of cytokines which lead directly to the death of infected pig-tailed macaques ...	1994	8057436
spontaneous substitutions in the vicinity of the v3 analog affect cell tropism and pathogenicity of simian immunodeficiency virus.	simian immunodeficiency virus (siv) exists within tissues of infected macaques as a mixture of diverse genotypes. the goal of this study was to investigate the biologic significance of this variation in terms of cellular tropism and pathogenicity. pcr was used to amplify and clone 3'-half genomes from the spleen of an immunodeficiency siv-infected pig-tailed macaque (macaca nemestrina). eight infectious clones were generated by ligation of respective 3' clones into a related sivsm 5' clone, and ...	1994	8139042
simian immunodeficiency virus sivsmmpbj 1.9 induces multinucleated giant cell formation in human peripheral blood monocytes.	sivsmmpbj 1.9 is an extremely virulent clone of the simian immunodeficiency virus sivsmmpbj 14 that causes an acute lethal disease in pigtail macaques, with death occurring 6 to 8 days after infection. the disease is characterized by bloody mucoid diarrhea, lymphoid hyperplasia, and giant cell pneumonia. we have developed an in vitro model for the production of multinucleated giant cells (mgcs) in which peripheral blood monocytes rapidly fuse to form mgcs when cultured in lymphocyte-conditioned ...	1994	8179965
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 ...	1994	8198870
intrarectal inoculation of macaques by the simian immunodeficiency virus, sivmne e11s: cd4+ depletion and aids.	macaca nemestrina and macaca fascicularis were inoculated with various doses of a single-cell clone of sivmne-infected hut 78 cells (e11s) by both the intravenous and intrarectal routes. animals inoculated intravenously at each dose seroconverted and virus was isolated from peripheral blood mononuclear cells, but only the high-dose intrarectally exposed macaques became viremic and seroconverted. however, some seronegative, virus isolation negative intrarectally inoculated macaques showed evidenc ...	1994	7731030
comparison of rates of intracellular metabolism of zidovudine in human and primate peripheral blood mononuclear cells.	3'-azido-3'-deoxythymidine (azt) is a drug of choice for the treatment of aids. on the basis of pharmacokinetic data, the nonhuman primate macaca nemestrina has been shown to be a suitable animal model for use in the study of the disposition of azt. however, since azt is activated to its metabolite, the azt triphosphate (azttp), intracellularly, we investigated the intracellular activation of azt in peripheral blood mononuclear cells (pbmcs) of healthy and simian immunodeficiency virus-infected ...	1994	7840577
genetic variation of the sivagm transmembrane glycoprotein in naturally and experimentally infected primates.	an in-frame stop codon prematurely truncating the transmembrane glycoprotein (tmp) is a common feature of many simian immunodeficiency virus, african green monkey strain (sivagm) molecular clones. the purpose of this study was to investigate the native form of the sivagm tmp in a naturally infected african green monkey (agm) and to study the fate of the stop codon following the passage of sivagm in primates.	1993	8397939
multiple viral determinants contribute to pathogenicity of the acutely lethal simian immunodeficiency virus sivsmmpbj variant.	simian immunodeficiency virus (siv) induces an immunodeficiency syndrome similar to human aids. although the disease course of siv-induced immunodeficiency is generally measured in months to years, a disease syndrome that results in death in 5 to 14 days has been described in pig-tailed macaques infected with the sivsmmpbj (pbj) strain. the purpose of this study was to derive an acutely lethal pbj molecular clone in order to study viral genes involved in pathogenesis. six infectious molecular cl ...	1993	8474153
acute infection of macaca nemestrina by human immunodeficiency virus type 1.	the pigtail macaque (macaca nemestrina) has a marked sensitivity to infection by simian immunodeficiency virus and human immunodeficiency virus type 2 (hiv-2). on this basis, we previously studied this species' susceptibility to hiv-1 and demonstrated infection in six macaques inoculated with either cell-associated hiv-1 or cell-free virus alone. this report expands upon our initial in vitro and in vivo findings. five laboratory-adapted and one primary clinical strain of hiv-1 replicated in vitr ...	1993	8101673
infection of rhesus and cynomolgus macaques with a rapidly fatal siv (sivsmm/pbj) isolate from sooty mangabeys.	a variant of simian immunodeficiency virus (sivsmm/pbj), isolated from a chronically infected pig-tailed macaque has been shown in previous studies to produce acutely fatal disease uniformly in pig-tailed macaques and in some rhesus macaques. the present study extends investigation of sivsmm/pbj pathogenesis in rhesus and cynomolgus monkeys. cynomolgus and rhesus macaques were found to be uniformly susceptible to infection, but as previously reported, the rhesus were found to not be uniform in t ...	1992	1457209
infection of macaca nemestrina by human immunodeficiency virus type-1.	after observations that macaca nemestrina were exceptionally susceptible to simian immunodeficiency virus and human immunodeficiency virus type-2 (hiv-2), studies of hiv-1 replication were initiated. several strains of hiv-1, including a recent patient isolate, replicated in vitro in peripheral blood mononuclear cells (pbmcs) and in cd4-positive m. nemestrina lymphocytes in a cd4-dependent fashion. eight animals were subsequently inoculated with either cell-associated or cell-free suspensions of ...	1992	1621083
method for detection of simian immunodeficiency virus neutralizing antibodies using a noncommercial antigen capture enzyme-linked immunosorbent assay.	a neutralization test (nt) using a noncommercial antigen capture enzyme-linked immunosorbent assay (elisa) to detect simian immunodeficiency virus (siv) growth in vitro was developed. the capture antibody was a mixture of purified macaque anti-siv immunoglobulin g (igg) and a monoclonal antibody to siv p27. captured antigens were detected by using purified macaque anti-siv igg conjugated to horseradish peroxidase. the nt reliably and sensitively detected differences when various amounts of siv w ...	1992	1624558
genetic differences accounting for evolution and pathogenicity of simian immunodeficiency virus from a sooty mangabey monkey after cross-species transmission to a pig-tailed macaque.	we determined the nucleotide sequences of two related isolates of simian immunodeficiency virus from the sooty mangabey monkey (sivsmm) that exhibit dramatic differences in virulence. these isolates are separated by one experimental cross-species transmission, from sooty mangabey to pig-tailed macaque. the parental virus (sivsmm9), nonpathogenic in the original host (sooty mangabeys), causes a chronic aids-like disease in macaques. in contrast, the variant virus (sivsmmpbj14) induces an acute le ...	1992	1727495
replication of an acutely lethal simian immunodeficiency virus activates and induces proliferation of lymphocytes.	a variant of simian immunodeficiency virus from sooty mangabey monkeys (sivsmm), termed sivsmmpbj14, was previously identified and shown to induce acute disease and death within 1 to 2 weeks of inoculation of pig-tailed macaques and mangabey monkeys (p. n. fultz, h. m. mcclure, d. c. anderson, and w. m. switzer, aids res. hum. retroviruses 5:397-409, 1989). sivsmmpbj14 differed from its parent virus, sivsmm9, not only in pathogenicity but also in multiple in vitro properties. as a first approach ...	1991	1870205
sequence analysis and acute pathogenicity of molecularly cloned sivsmm-pbj14.	the pbj14 isolate of simian immunodeficiency virus from sooty mangabey monkeys (sivsmm-pbj14) is the most acutely pathogenic primate lentivirus so far described, always causing fatal disease in pig-tailed macaques (macaca nemestrina) within 8 days of inoculation. as a first step in identifying viral genes and gene products that influence pathogenicity, the sivsmm-pbj14 genome was amplified by the polymerase chain reaction as 5' and 3' genomic halves of 5.1 and 5.8 kilobases, respectively, and mo ...	1990	1971917
inoculation of macaca fascicularis with simian immunodeficiency virus, sivmne immunologic, serologic, and pathologic changes.	previous studies had tested the susceptibility of two macaque species, macaca nemestrina and m. mulatta, to infection with the primate lymphotropic lentivirus sivmne. in this report we describe the results obtained after infecting eleven m. fascicularis with sivmne. six of the animals had previously been immunized with a recombinant vaccinia virus expressing the envelope gene of hiv-1. all eleven animals became seropositive. to date ten animals have died 43 to 155 weeks post infection of an aids ...	1990	2231689
transmission of the simian immunodeficiency virus sivmne in macaques and baboons.	a primate lymphotropic lentivirus was isolated on hut 78 cells after cocultivation of a lymph node from a macaque that died with malignant lymphoma. in earlier studies siv/mne was inoculated into 17 macaques and two baboons. all of the macaques became viremic and seropositive. fifteen of the macaques succumbed to a classic aids-like disease, whereas the baboons did not become viremic. the siv/mne virus has now been molecularly cloned and inoculated into macaca nemestrina and baboons. a new trans ...	1989	2547959
molecularly cloned simian immunodeficiency virus sivagm3 is highly divergent from other sivagm isolates and is biologically active in vitro and in vivo.	simian immunodeficiency viruses have been isolated from african green monkeys originating from ethiopia. a molecular clone, termed sivagm3, was found to be highly divergent from sivagmtyo-1 in terms of its restriction map and partial nucleotide sequence. a premature stop codon present in the transmembrane protein of sivagm tyo-1 was absent in sivagm3. sivagm3 was biologically active in vitro and in vivo and displayed characteristics reminiscent of the wild-type virus. biological activity was dem ...	1989	2685353
identification and biologic characterization of an acutely lethal variant of simian immunodeficiency virus from sooty mangabeys (siv/smm).	a virus pool isolated from lymphoid tissue of a macaque (pbj) infected for 14 months with siv/smm was found to be associated with acute disease and death. six of six pig-tailed macaques, one of three rhesus macaques, and three of four siv/smm-seronegative mangabeys developed acute disease within 5 days and died from 7 to 13 days postinoculation; however, neither of two siv/smm-infected mangabeys died or developed disease. the virus associated with acute disease and death was shown by electron mi ...	1989	2765298
inoculation of baboons and macaques with simian immunodeficiency virus/mne, a primate lentivirus closely related to human immunodeficiency virus type 2.	a primate lymphotropic lentivirus was isolated on the human t-cell line hut 78 after cocultivation of a lymph node from a pig-tailed macaque (macaca nemestrina) that had died with malignant lymphoma. this isolate, originally designated m. nemestrina immunodeficiency virus (mniv) and now classified as simian immunodeficiency virus (siv/mne), was inoculated intravenously into three juvenile rhesus monkeys (macaca mulatta), three juvenile pig-tailed macaques (m. nemestrina), and two juvenile baboon ...	1988	3285032
molecular characterization of gag proteins from simian immunodeficiency virus (sivmne).	a simian immunodeficiency virus (siv) designated sivmne was isolated from a pig-tailed macaque with lymphoma housed at the university of washington regional primate research center, seattle. to better establish the relationship of sivmne to other immunodeficiency viruses, we purified and determined the partial amino acid sequences of six structural proteins (p1, p2, p6, p8, p16, and p28) from sivmne and compared these amino acid sequences to the translated nucleotide sequences of sivmac and huma ...	1988	3292789