Rapid CD4 ⁺ T-Cell Loss Induced by Human Immunodeficiency Virus Type 1 _NC in 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.

Lessons from Viral Superinfections for HIV-1 Vaccine Design

“…Before any conclusive case had been reported in humans, HIV-1 superinfection was induced experimentally in chimpanzees, and the second infection produced a slower immune deterioration and more efficient control of viremia compared to the initial infection [16]. This report was followed by additional studies documenting HIV-1 and SIV superinfections in monkeys [16][17][18][19][20][21][22]. However, the extent to which these results can be applied to human HIV-1 superinfection remains to be thoroughly determined.…”

Death of effector memory T cells characterizes AIDS

“…Studies performed in pathogenic and nonpathogenic primate models of HIV or simian (SIV) immunodeficiency virus infection have identified during the chronic phase a correlation between the induction of enhanced in vitro T cell apoptosis and the in vivo pathogenic nature of the retroviral infection (16,19,33,(37)(38)(39). Thus, enhanced levels of apoptosis in CD4+ T cells were observed in the models leading to AIDS: HIV-1infected human individuals, Rhesus Macaques (RMs) infected with a pathogenic strain of SIVmac, and chimpanzees infected with a pathogenic strain of SIVcpz (37,40). In contrary, no apoptosis was observed in AGMs or SMs (19,33).…”