Rapid CD4⁺T-Cell Loss Induced by Human Immunodeficiency Virus Type 1_NCin Uninfected and Previously Infected Chimpanzees

Abstract

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/l 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/l 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.

Apoptosis in SIV infection

“…53,77 Furthermore, studies performed in pathogenic and nonpathogenic primate models of HIV or SIV infection during the chronic asymptomatic phase have identified a correlation between the induction of enhanced in vitro T-cell apoptosis and the in vivo pathogenic nature of the retroviral infection 27,44,51,78-84 ( Figure 1b). Thus, enhanced levels of apoptosis in CD4 þ T cells were observed in HIV-1-infected human individuals, rhesus macaques infected with a pathogenic strain of SIVmac, and chimpanzees infected with a pathogenic strain of SIVcpz leading to AIDS, 78,85 while enhanced CD8 T-cell apoptosis was observed in both pathogenic and nonpathogenic primate models. In contrast, no increased propensity of either CD4 þ or CD8 þ T-cell in vitro apoptosis and normal levels of T-cell apoptosis in the Tcell-dependent areas of the LN were observed in either naturally or experimentally SIV-infected SMs.…”

Nef Proteins from Simian Immunodeficiency Virus-Infected Chimpanzees Interact with p21-Activated Kinase 2 and Modulate Cell Surface Expression of Various Human Receptors

“…ϩ -T-cell depletion or disease (51,52,56,66). Host, viral, or environmental factors could explain the different outcome of HIV-1 and SIVcpz infection of humans and chimpanzees, respectively.…”

Foci of Endemic Simian Immunodeficiency Virus Infection in Wild-Living Eastern Chimpanzees ( Pan troglodytes schweinfurthii )

“…Fifteen of these had been experimentally infected with HIV-1 more than a decade earlier as part of AIDS research studies (Table 1). Although five had significantly reduced CD4 counts (less than 200/mm 3 ; normal range 1,000 to 2,500/mm 3 ), none exhibited signs of clinical illness (35,36,39). Fecal and urine samples were also obtained from four SIVcpz-infected chimpanzees.…”