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1.
Novembre FJ de Rosayro J Nidtha S O'Neil SP Gibson TR Evans-Strickfaden T Hart CE McClure HM 《Journal of virology》2001,75(3):1533-1539
To investigate the pathogenicity of a virus originating in a chimpanzee with AIDS (C499), two chimpanzees were inoculated with a plasma-derived isolate termed human immunodeficiency virus type 1(NC) (HIV-1(NC)). A previously uninfected chimpanzee, C534, experienced rapid peripheral CD4(+) T-cell loss to fewer than 26 cells/microl by 14 weeks after infection. CD4(+) T-cell depletion was associated with high plasma HIV-1 loads but a low virus burden in the peripheral lymph node. The second chimpanzee, C459, infected 13 years previously with HIV-1(LAV), experienced a more protracted course of peripheral CD4(+) T-cell loss after HIV-1(NC) inoculation, resulting in fewer than 200 cells/microl by 96 weeks postinoculation. The quantities of viral RNA in the plasma and peripheral lymph node from C459 were below the lower limits of detection prior to inoculation with HIV-1(NC) but were significantly and persistently increased after superinfection, with HIV-1(NC) representing the predominant viral genotype. These results show that viruses derived from C499 are more pathogenic for chimpanzees than any other HIV-1 isolates described to date. 相似文献
2.
Molecular Cloning and Characterization of Viruses Isolated from Chimpanzees with Pathogenic Human Immunodeficiency Virus Type 1 Infections 总被引:3,自引:1,他引:2
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We have previously described the development of AIDS in a chimpanzee (C499) infected with human immunodeficiency virus type 1 (HIV-1) and the subsequent pathogenic HIV-1 infection in another chimpanzee (C455) transfused with blood from C499 (F. J. Novembre et al., J. Virol. 71:4086–4091, 1997). In the present study, two virus isolates were derived from these animals: HIV-1JC from peripheral blood mononuclear cells (PBMC) of C499, and HIV-1NC from plasma of C455. These virus isolates were used to generate two infectious molecular clones, termed HIV-1JC16 and HIV-1NC7 (JC16 and NC7, respectively). Comparative analyses of the sequences of the two clones showed that they were highly interrelated but distinct. Based on heteroduplex mobility assays, JC16 and NC7 appear to represent dominant viruses in the uncloned stock population. Compared with amino acid sequences of the parental viruses HIV-1SF2, HIV-1LAV-1b, and HIV-1NDK, JC16 and NC7 showed a number of differences, including insertions, deletions, and point mutations spread throughout the genome. However, insertion/deletion footprints in several genes of both JC16 and NC7 suggested that recombination between SF2 and LAV-1b could have occurred, possibly contributing to the generation of a pathogenic virus. Comparative in vitro analyses of the molecular clones and the uncloned stocks of HIV-1JC and HIV-1NC revealed that these viruses had strikingly similar replicative abilities in mitogen-stimulated PBMC and in macrophages. Compared to the SF2 and LAV-1b isolates of HIV-1, HIV-1JC and HIV-1NC isolates were more similar to LAV-1b with respect to the ability to replicate in mitogen-stimulated PBMC and macrophages. These viruses should prove to be useful in mapping determinants of pathogenesis. 相似文献
3.
Isolation and characterization of a syncytium-inducing, macrophage/T-cell line-tropic human immunodeficiency virus type 1 isolate that readily infects chimpanzee cells in vitro and in vivo. 总被引:12,自引:10,他引:2
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R Shibata M D Hoggan C Broscius G Englund T S Theodore A Buckler-White L O Arthur Z Israel A Schultz H C Lane et al. 《Journal of virology》1995,69(7):4453-4462
Fresh human immunodeficiency virus type 1 (HIV-1) isolates from patients with AIDS were screened for infectivity in chimpanzee peripheral blood mononuclear cells (PBMC) to identify strains potentially able to generate high virus loads in an inoculated animal. Only 3 of 23 isolates obtained were infectious in chimpanzee cells. Of these three, only one (HIV-1DH12) was able to initiate a productive infection in PBMC samples from all 25 chimpanzees tested. HIV-1DH12 tissue culture infections were characterized by extremely rapid replication kinetics, profound cytopathicity, and tropism for chimp and human PBMC, primary human macrophage, and several human T-cell lines. An infection was established within 1 week of inoculating a chimpanzee with 50 50% tissue culture infective doses of HIV-1DH12; cell-free virus was recovered from the plasma at weeks 1, 2, and 4 and was associated with the development of lymphadenopathy. Virus loads during the primary infection and at 6 months postinoculation were comparable to those reported in HIV-1-seropositive individuals. 相似文献
4.
Loss of CD4+ T Cells in Human Immunodeficiency Virus Type 1-Infected Chimpanzees Is Associated with Increased Lymphocyte Apoptosis
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Supportive evidence that apoptosis contributes to loss of CD4+ lymphocytes in human immunodeficiency virus type 1 (HIV-1)-infected humans comes from an apparent lack of abnormal apoptosis in apathogenic lentivirus infections of nonhuman primates, including HIV-1 infection of chimpanzees. Two female chimpanzees were inoculated, one cervically and the other intravenously, with HIV-1 derived from the LAI/LAV-1b strain, which was isolated from a chimpanzee infected with the virus for 8 years. Within 6 weeks of infection, both recipient chimpanzees developed a progressive loss of CD4+ T cells which correlated with persistently high viral burdens and increased levels of CD4+ T-cell apoptosis both in vitro and in vivo. Lymph nodes from both animals also revealed evidence of immune hyperactivation. Intermediate levels of T-cell apoptosis in both peripheral blood and lymph nodes were seen in a third chimpanzee that had been infected with the LAI/LAV-1b strain for 9 years; this animal has maintained depressed CD4/CD8 T-cell ratios for the last 3 years. Similar analyses of cells from 4 uninfected animals and 10 other HIV-1-infected chimpanzees without loss of CD4+ cells revealed no difference in levels of apoptosis in these two control groups. These results demonstrate a correlation between immune hyperactivation, T-cell apoptosis, and chronic loss of CD4+ T cells in HIV-1-infected chimpanzees, providing additional evidence that apoptosis is an important factor in T-cell loss in AIDS. Furthermore, the results show that some HIV-1 strains are pathogenic for chimpanzees and that this species is not inherently resistant to HIV-1-induced disease. 相似文献
5.
To identify mucosal immunity in HIV-infected chimpanzees, IgG, IgA, and IgM from plasma, saliva, rectal swabs, vaginal washes, semen, and urethral washes were tested from four male and three female HIV-1IIIB infected chimpanzees. The level of HIV infections in the seven chimpanzees were classified as high, intermediate and low depending on the number of HIV-1 infected cells per 107 peripheral blood mononuclear cells (PBMC). One male chimpanzee had a relatively high viral load, two males and two females had moderate viral loads and one male and one female had low levels of infection. All seven animals had plasma antibody. The principal finding was that nonclassical mucosal antibodies of the IgG isotype were the predominant antibody in the saliva, rectal swabs, vaginal washes, semen, and urethral washes of infected animals. All plasma and mucosal samples were negative for IgM antibodies. The results show that HIV-1 specific IgG responses and not sIgA predominate at mucosal surfaces of HIV-1IIIB infected chimpanzees. A trend was observed in which high viral loads correlated with high plasma IgG, IgA and sIgA titers. An overall correlation between relatively high virus loads and high amounts of mucosal IgG was also found. 相似文献
6.
近年来,一些研究发现,GBV-C/HIV共感染可延缓HIV感染疾病的进程,然而也有一些研究得出不同的结论.本研究收集我国安徽省阜阳市HIV血清学阳性的既往献血员血浆标本,对其进行GBV-C感染的检测,研究GBV-C/HIV共感染与HIV病毒载量和CD4 T淋巴细胞绝对计数的关系.用RT-PCR和酶联免疫法检测,在203人中检出GBV-C感染52例,显示该人群GBV-C的感染率为25.6%,男性感染者(35例,67.3%)高于女性感染者(17例,32.7%).分析发现,GBV-C感染与未感染两组患者的CD4 T淋巴细胞绝对计数和HIV病毒载量数据均无统计学差异.本研究中的HIV-1感染者均未接受ART治疗,因而排除了治疗对疾病进展的影响.研究结果显示,在HIV-1感染晚期的献血人群,GBV-C/HIV共感染对CD4细胞和病毒复制水平无显著影响.由于本研究对象中无HIV-1早期感染者,因而不能判断GBV-C在HIV-1感染的早期对疾病进展有无影响. 相似文献
7.
A chimpanzee-passaged human immunodeficiency virus isolate is cytopathic for chimpanzee cells but does not induce disease.
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M Watanabe D J Ringler P N Fultz J J MacKey J E Boyson C G Levine N L Letvin 《Journal of virology》1991,65(6):3344-3348
The human immunodeficiency virus type 1 (HIV-1) readily infects both humans and chimpanzees, but the pathologic outcomes of infection in these two species differ greatly. In attempts to identify virus-cell interactions that might account for this differential pathogenicity, chimpanzee peripheral blood lymphocytes and bone marrow macrophages were assessed in vitro for their ability to support the replication of several HIV-1 isolates. Although the IIIb, RF, and MN isolates did not readily infect chimpanzee peripheral blood lymphocytes, an isolate of HIV-1 passaged in vivo in chimpanzees not only replicated well in both chimpanzee peripheral blood lymphocytes and bone marrow macrophages but also was cytopathic for chimpanzee CD4+ lymphocytes. Because no evidence of HIV-induced disease has been observed in chimpanzees infected with this isolate, in vitro replication to high titers with concomitant loss of CD4+ cells is not, in this instance, a correlate of pathogenicity. These observations, therefore, indicate that caution must be used when making extrapolations from in vitro data to in vivo pathogenesis. 相似文献
8.
Edward J. D. Greenwood Fabian Schmidt Ivanela Kondova Henk Niphuis Vida L. Hodara Leah Clissold Kirsten McLay Bernadette Guerra Sharon Redrobe Luis D. Giavedoni Robert E. Lanford Krishna K. Murthy Fran?ois Rouet Jonathan L. Heeney 《PLoS pathogens》2015,11(9)
The virus-host relationship in simian immunodeficiency virus (SIV) infected chimpanzees is thought to be different from that found in other SIV infected African primates. However, studies of captive SIVcpz infected chimpanzees are limited. Previously, the natural SIVcpz infection of one chimpanzee, and the experimental infection of six chimpanzees was reported, with limited follow-up. Here, we present a long-term study of these seven animals, with a retrospective re-examination of the early stages of infection. The only clinical signs consistent with AIDS or AIDS associated disease was thrombocytopenia in two cases, associated with the development of anti-platelet antibodies. However, compared to uninfected and HIV-1 infected animals, SIVcpz infected animals had significantly lower levels of peripheral blood CD4+ T-cells. Despite this, levels of T-cell activation in chronic infection were not significantly elevated. In addition, while plasma levels of β2 microglobulin, neopterin and soluble TNF-related apoptosis inducing ligand (sTRAIL) were elevated in acute infection, these markers returned to near-normal levels in chronic infection, reminiscent of immune activation patterns in ‘natural host’ species. Furthermore, plasma soluble CD14 was not elevated in chronic infection. However, examination of the secondary lymphoid environment revealed persistent changes to the lymphoid structure, including follicular hyperplasia in SIVcpz infected animals. In addition, both SIV and HIV-1 infected chimpanzees showed increased levels of deposition of collagen and increased levels of Mx1 expression in the T-cell zones of the lymph node. The outcome of SIVcpz infection of captive chimpanzees therefore shares features of both non-pathogenic and pathogenic lentivirus infections. 相似文献
9.
Human immunodeficiency virus (HIV) from experimentally infected chimpanzees: isolation and characterization 总被引:2,自引:0,他引:2
B A Castro C M Walker M Tateno C Cheng-Mayer R Heberling J W Eichberg J A Levy 《Journal of medical primatology》1989,18(3-4):337-342
Human immunodeficiency virus-1 (HIV-1) isolates obtained from chimpanzees that had undergone various immunosuppressive treatments were characterized by growth on various primary cells and cell lines as well as by restriction endonuclease analysis. Viruses recovered from animals inoculated with uncloned HIV showed genetic variation from the original inoculum, whereas viruses isolated from an animal infected with a molecular clone of HIV did not. In some cases, virus recovery was possible only after enrichment for CD4+ cells by panning, inoculation with a chimpanzee cytomegalovirus, or a combination of these procedures. These findings indicate a role for viral and host cofactors in the control of virus replication and suggest explanations for the absence of clinical manifestations in HIV-infected chimpanzees. 相似文献
10.
Resistance of previously infected chimpanzees to successive challenges with a heterologous intraclade B strain of human immunodeficiency virus type 1. 总被引:2,自引:2,他引:0
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R Shibata C Siemon M W Cho L O Arthur S M Nigida Jr T Matthews L A Sawyer A Schultz K K Murthy Z Israel A Javadian P Frost R C Kennedy H C Lane M A Martin 《Journal of virology》1996,70(7):4361-4369
To test whether the protective effects of attenuated simian immunodeficiency virus vaccines in macaques were applicable to the human immunodeficiency virus type 1 (HIV-1)-chimpanzee system, two groups of animals, previously infected with HIV-1(IIIB) or HIV-1(SF2) were each challenged with a heterologous clade B virus, HIV-1(DH12). Following challenge, the parameters measured included virus isolation (from plasma, peripheral blood mononuclear cells, and lymph node tissue); quantitative DNA PCR using primers capable of distinguishing HIV-1(IIIB), HIV-1(SF2), and HIV-1(DH12) from one another; and serologic assays to monitor changes in binding and neutralizing antibodies. In contrast to an HIV-1-naive chimpanzee that rapidly became infected following the inoculation of HIV-1(DH12), the two chimpanzees previously infected with HIV-1(IIIB) resisted repeated and escalating inoculations of HIV-1(DH12), as monitored by virus isolation and PCR. The two animals previously infected with HIV-1(SF2) became infected with HIV-1(DH12) but in contrast to the case with the HIV-1-naive chimpanzee, no cell-free viral RNA was detected in the plasma by the branched DNA procedure and levels of peripheral blood mononuclear cell-associated viral DNA were reduced 35- to 50-fold. 相似文献
11.
D.M. Boldt-Houle S.M. Nigida C.R. Rinaldo G.D. Ehrlich 《Journal of medical primatology》1994,23(8):432-441
Using a panel of human T-cell receptor (TCR) variable region β chain (Vβ) polymerase chain reaction (PCR) primers, we performed cross-sectional and longitudinal analyses of the TCR Vβ repertoire in naive and HIV-1 infected chimpanzees. We demonstrate that our TCR PCR primer panel will support amplification of chimpanzee cDNA from most of the TCR Vβ families. However, no differences in TCR Vβ expression were found between the naive and HIV-1 infected chimpanzees, unlike the TCR Vβ repertoire perturbation found in HIV-1 infected human subjects. This finding suggests that a complete TCR repertoire in HIV-1 infected chimpanzees is associated with the maintenance CD4 + T-cell numbers and lack of progression to AIDS. 相似文献
12.
Increased neutralization sensitivity and reduced replicative capacity of human immunodeficiency virus type 1 after short-term in vivo or in vitro passage through chimpanzees
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Beaumont T Broersen S van Nuenen A Huisman HG de Roda Husman AM Heeney JL Schuitemaker H 《Journal of virology》2000,74(17):7699-7707
Development of disease is extremely rare in chimpanzees when inoculated with either T-cell-line-adapted neutralization-sensitive or primary human immunodeficiency virus type 1 (HIV-1), at first excluding a role for HIV-1 neutralization sensitivity in the clinical course of infection. Interestingly, we observed that short-term in vivo and in vitro passage of primary HIV-1 isolates through chimpanzee peripheral blood mononuclear cells (PBMC) resulted in a neutralization-sensitive phenotype. Furthermore, an HIV-1 variant reisolated from a chimpanzee 10 years after experimental infection was still sensitive to neutralization by soluble CD4, the CD4 binding site recognizing antibody IgG1b12 and autologous chimpanzee serum samples, but had become relatively resistant to neutralization by polyclonal human sera and neutralizing monoclonal antibodies. The initial adaptation of HIV-1 to replicate in chimpanzee PBMC seemed to coincide with a selection for viruses with low replicative kinetics. Neither coreceptor usage nor the expression level of CD4, CCR5, or CXCR4 on chimpanzee PBMC compared to human cells could explain the phenotypic changes observed in these chimpanzee-passaged viruses. Our data suggest that the increased neutralization sensitivity of HIV-1 after replication in chimpanzee cells may in part contribute to the long-term asymptomatic HIV-1 infection in experimentally infected chimpanzees. 相似文献
13.
The inability of human immunodeficiency virus to infect chimpanzee monocytes can be overcome by serial viral passage in vivo.
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H E Gendelman G D Ehrlich L M Baca S Conley J Ribas D C Kalter M S Meltzer B J Poiesz P Nara 《Journal of virology》1991,65(7):3853-3863
Studies of lentivirus infection in ruminants, nonhuman primates, and humans suggest that virus infection of macrophages plays a central role in the disease process. To investigate whether human immunodeficiency virus type 1 (HIV-1) can infect chimpanzee macrophages, we recovered monocytes from peripheral blood mononuclear cells of HIV-1-negative animals and inoculated these and control human monocytes with a panel of four human-passaged monocytotropic virus strains and one chimpanzee-passaged isolate. HIV-1 infected human monocytes synthesized proviral DNA, viral mRNA, p24 antigen, and progeny virions. In contrast, except for the chimpanzee-passaged HIV-1 isolate, chimpanzee monocytes failed to support HIV-1 replication when cultured under both identical and a variety of other conditions. Proviral DNA was demonstrated only at background levels in these cell cultures by polymerase chain reaction for gag- and env-related sequences. Interestingly, the chimpanzee-passaged HIV-1 isolate did not replicate in human monocytes; viral p24 antigens and progeny virions were not detected. The same monocytotropic panel of HIV-1 strains replicated in both human and chimpanzee CD4+ T lymphoblasts treated with phytohemagglutinin and interleukin-2. The failure of HIV-1 to infect chimpanzee monocytes, which can be overcome by serial in vivo viral passage, occurs through a block early in the viral life cycle. 相似文献
14.
Increased viral burden and cytopathicity correlate temporally with CD4+ T-lymphocyte decline and clinical progression in human immunodeficiency virus type 1-infected individuals. 总被引:47,自引:36,他引:11
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The rate of clinical progression is variable among individuals infected with human immunodeficiency virus type 1 (HIV-1). Changes in viral burden which correlate with disease status have been demonstrated in cross-sectional studies; however, a detailed longitudinal study of the temporal relationship between viral burden, CD4+ T-cell numbers, and clinical status throughout the course of infection has not been reported. Multiple longitudinal blood samples were obtained from four HIV-1-infected individuals with clinically divergent profiles. Levels of HIV-1 were measured in sequential samples of peripheral blood mononuclear cells, using both end-point dilution cultures and quantitative polymerase chain reaction methods. Serial HIV-1 isolates from each case were also evaluated to determine their biological properties in vitro. For the three patients with clinical progression, a dramatic increase in the level of HIV-1 was observed concurrent with or prior to a marked drop in CD4+ T lymphocytes. This increase in viral burden was temporally associated with the emergence of a more cytopathic viral phenotype. In contrast, consistently low levels of HIV-1 were observed in the one patient who was clinically and immunologically stable for more than a decade. Moreover, viral isolates from this patient were less cytopathic in vitro compared with HIV-1 isolates from those patients with disease progression. The temporal association between increased viral burden and CD4+ T-cell decline suggests a direct role for HIV-1 in the cytopathology of CD4+ T cells in vivo. Our results indicate that the pathogenic mechanisms responsible for CD4+ T-cell depletion may be related to both quantitative and qualitative changes in HIV-1. 相似文献
15.
In vitro susceptibility of T lymphocytes from chimpanzees (Pan troglodytes) to human herpesvirus 6 (HHV-6): a potential animal model to study the interaction between HHV-6 and human immunodeficiency virus type 1 in vivo. 总被引:2,自引:1,他引:1
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The in vitro susceptibility of several nonhuman primate species to human herpesvirus 6 (HHV-6) was investigated. Only peripheral blood mononuclear cells from chimpanzees (Pan troglodytes) were found permissive to productive infection by HHV-6, indicating that the host range of HHV-6, albeit limited, may not be restricted to Homo sapiens. However, natural HHV-6 infection in chimpanzees, as well as in the other species tested, could not be documented by serological analysis. As previously observed with human cells, HHV-6 infection of chimpanzee peripheral blood mononuclear cells was highly cytopathic and the infected cells exhibited phenotypic features of activated T lymphocytes. Although in humans the majority of HHV-6-infected lymphocytes displayed the CD4 antigen, in chimpanzees a mixed CD4+ and CD8+ phenotype was observed. HHV-6 was also shown to productively coinfect individual chimpanzee T cells with human immunodeficiency virus type 1, resulting in an accelerated induction of cytopathicity. In light of these findings, we propose the utilization of chimpanzees as a potential animal model system to investigate the in vivo interaction between HHV-6 and human immunodeficiency virus type 1 and its relevance to the development of acquired immune deficiency syndrome. 相似文献
16.
Extensive Diversification of Human Immunodeficiency Virus Type 1 Subtype B Strains during Dual Infection of a Chimpanzee That Progressed to AIDS 总被引:2,自引:1,他引:1
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A chimpanzee (C-499) infected for more than 9 years with two subtype B isolates of human immunodeficiency virus type 1 (HIV-1), one (HIV-1SF2) that replicates poorly and one (HIV-1LAV-1b) that replicates efficiently in chimpanzees, died of AIDS 11 years after initial infection (F. J. Novembre et al., J. Virol. 71:4086–4091, 1997). Nucleotide sequence and phylogenetic analyses of the C2 to V5 region of env (C2-V5env) in proviral DNA from peripheral blood lymphocytes obtained 22 months before death revealed two distinct virus populations. One of these populations appeared to be a recombinant in env, having the V3 loop from HIV-1SF2 and the V4-V5 region from HIV-1LAV-1b; the other population had evolved from HIV-1LAV-1b. In addition to C2-V5env, the entire p17gag and nef genes were sequenced; however, based on nucleotide sequences and phlyogeny, whether the progenitor of the p17gag and nef genes was SF2 or LAV-1b could not be determined. Compared to the two original viruses, the divergence of all clones of C2-V5env ranged from 9.37 to 20.2%, that of p17gag ranged from 3.11 to 9.29%, and that of nef ranged from 4.02 to 7.9%. In contrast, compared to the maximum variation of 20.2% in C2-V5env for C-499, the maximum diversities in C2-V5env in proviruses from two chimpanzees infected with HIV-1LAV-1b for 9 and 10 years were 9.65 and 2.48%, respectively. These results demonstrate that (i) two distinct HIV-1 populations can coexist and undergo extensive diversification in chimpanzees with progressive HIV-1-induced disease and (ii) recombination between two subtype B strains occurred even though the second strain was inoculated 15 months after the first one. Furthermore, evaluation of env genes from three chimpanzees infected with the same strain suggests that the magnitude of HIV-1 diversification could be related to higher viral burdens, manifestations of disease, and/or dual infection. 相似文献
17.
Longitudinal follow up of SIVmac pathogenesis in rhesus macaques of Chinese origin: emergence of B cell lymphoma 总被引:5,自引:0,他引:5
Ling B Veazey RS Penedo C Xu K Lifson JD Marx PA 《Journal of medical primatology》2002,31(4-5):154-163
Two subspecies of rhesus (Rh) macaques, the Chinese (Ch) and Indian (Ind) subspecies were infected intravenously with 100TCID50 SIVmac239. CD4+, CD8+ T cells, plasma viral loads, depletion of intestinal lymphocytes with memory phenotype, humoral immune responses and clinical courses were monitored for 600 days. The pathogenesis of SIVmac was also compared with primary human immunodeficiency virus (HIV) infection of humans. Plasma viral loads in Ch Rh were lower in the acute and chronic phases compared with Ind Rh. SIVmac pathogenesis in Ch Rh was closer to virus loads in untreated HIV infected humans. Ch Rh had higher CD4/CD8 ratios, stronger antibody responses and interestingly, less depletion of intestinal memory CCR5+ CD4+ T lymphocytes compared with Ind Rh. One Ch Rh developed B cell origin lymphoma at 570 days post-infection, the first such report in this subspecies. Three of four Ind Rh developed AIDS within 6 months. The findings indicate that Ch Rh are more resistant to SIVmac pathogenesis compared with Ind Rh and that Ch Rh paralleled HIV-1 infections in untreated adult humans. The SIVmac infected Ch Rh subspecies are an acceptable model for HIV/AIDS. 相似文献
18.
Adaptation of HIV-1 to its human host 总被引:5,自引:0,他引:5
Wain LV Bailes E Bibollet-Ruche F Decker JM Keele BF Van Heuverswyn F Li Y Takehisa J Ngole EM Shaw GM Peeters M Hahn BH Sharp PM 《Molecular biology and evolution》2007,24(8):1853-1860
Human immunodeficiency virus type 1 (HIV-1) originated from three independent cross-species transmissions of simian immunodeficiency virus (SIVcpzPtt) infecting chimpanzees (Pan troglodytes troglodytes) in west central Africa, giving rise to pandemic (group M) and non-pandemic (groups N and O) clades of HIV-1. To identify host-specific adaptations in HIV-1 we compared the inferred ancestral sequences of HIV-1 groups M, N and O to 12 full length genome sequences of SIVcpzPtt and four of the outlying but closely related SIVcpzPts (from P. t. schweinfurthii). This analysis revealed a single site that was completely conserved among SIVcpzPtt strains but different (due to the same change) in all three groups of HIV-1. This site, Gag-30, lies within p17, the gag-encoded matrix protein. It is Met in SIVcpzPtt, underwent a conservative replacement by Leu in one lineage of SIVcpzPts but changed radically to Arg on all three lineages leading to HIV-1. During subsequent diversification this site has been conserved as a basic residue (Arg or Lys) in most lineages of HIV-1. Retrospective analysis revealed that Gag-30 had reverted to Met in a previous experiment in which HIV-1 was passaged through chimpanzees. To examine whether this substitution conferred a species specific growth advantage, we used site-directed mutagenesis to generate variants of these chimpanzee-adapted HIV-1 strains with Lys at Gag-30, and tested their replication in both human and chimpanzee CD4+ T lymphocytes. Remarkably, viruses encoding Met replicated to higher titers than viruses encoding Lys in chimpanzee T cells, but the opposite was found in human T cells. Taken together, these observations provide compelling evidence for host-specific adaptation during the emergence of HIV-1 and identify the viral matrix protein as a modulator of viral fitness following transmission to the new human host. 相似文献
19.
HIV-infected humans, but not chimpanzees, have circulating cytotoxic T lymphocytes that lyse uninfected CD4+ cells 总被引:10,自引:0,他引:10
J M Zarling J A Ledbetter J Sias P Fultz J Eichberg G Gjerset P A Moran 《Journal of immunology (Baltimore, Md. : 1950)》1990,144(8):2992-2998
It has been suggested that autoimmune phenomena contribute to the depletion of CD4+ T cells and the development of AIDS in HIV-1 infected humans based, in part, on observations that some HIV-1-infected humans have autoantibodies reactive with Ag expressed on uninfected CD4+ cells. In this study, 11 of 14 asymptomatic HIV-1-infected homosexuals and hemophiliacs, but none of 17 uninfected homosexuals or heterosexuals, were found to have cytotoxic lymphocytes in blood that can lyse uninfected CD4+ T cells from humans and chimpanzees but not human B lymphoblastoid cells or mouse T cells. The cytotoxic PBL were concluded to be CTL rather than NK cells, with the phenotype being CD3+, TCR-1 alpha beta+, CD8+, CD4-, CD16- based on findings that PBL-mediated lysis of uninfected CD4+ cells was 1) blocked by a mAb to CD3, which inhibits CTL but not NK activity; 2) diminished by treatment of PBL with a mAb to CD8 and C, but not by treatment with mAb to CD4 or CD16 and C; and 3) blocked by mAb WT31 directed against the TCR-1 alpha beta. In contrast, PBL from HIV-1-infected chimpanzees, which to date have not developed AIDS, lacked detectable CTL lytic for uninfected CD4+ cells. 相似文献
20.
Nef proteins from simian immunodeficiency virus-infected chimpanzees interact with p21-activated kinase 2 and modulate cell surface expression of various human receptors
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Kirchhoff F Schindler M Bailer N Renkema GH Saksela K Knoop V Müller-Trutwin MC Santiago ML Bibollet-Ruche F Dittmar MT Heeney JL Hahn BH Münch J 《Journal of virology》2004,78(13):6864-6874
The accessory Nef protein allows human immunodeficiency virus type 1 (HIV-1) to persist at high levels and to cause AIDS in infected humans. The function of HIV-1 group M subtype B nef alleles has been extensively studied, and a variety of in vitro activities believed to be important for viral pathogenesis have been established. However, the function of nef alleles derived from naturally simian immunodeficiency virus (SIV)-infected chimpanzees, the original host of HIV-1, or from the HIV-1 N and O groups resulting from independent zoonotic transmissions remains to be investigated. In the present study we demonstrate that SIVcpz and HIV-1 group N or O nef alleles down-modulate CD4, CD28, and class I or II MHC molecules and up-regulate surface expression of the invariant chain (Ii) associated with immature major histocompatibility complex (MHC) class II. Furthermore, the ability of Nef to interact with the p21-activated kinase 2 was generally conserved. The functional activity of HIV-1 group N and O nef genes did not differ significantly from group M nef alleles. However, SIVcpz nef genes as a group showed a 1.8- and 2.0-fold-higher activity in modulating CD28 (P = 0.0002) and Ii (P = 0.016) surface expression, respectively, but were 1.7-fold less active in down-regulating MHC class II molecules (P = 0.006) compared to HIV-1 M nef genes. Our finding that primary SIVcpz nef alleles derived from naturally infected chimpanzees modulate the surface expression of various human cellular receptors involved in T-cell activation and antigen presentation suggests that functional nef genes helped the chimpanzee virus to persist efficiently in infected humans immediately after zoonotic transmission. 相似文献