Phenotypic and Functional Parameters of Cellular Immunity in a Chimpanzee with a Naturally Acquired Simian Immunodeficiency Virus Infection

Abstract

The cellular immunologic and virologic status of a chimpanzee, naturally infected with a human immunodeficiency virus type 1 (HIV-1)-like lentivirus (SIVcpz-ant), was compared longitudinally with those of 3 HIV-1-infected and 5 uninfected chimpanzees for a period of 49 months. Evidence of immune deficiency was not observed in the HIV-1-infected chimpanzees, nor could virus be isolated from plasma. Virus could be isolated from plasma of the SIVcpz-ant-infected chimpanzee, but clinical signs of immune deficiency were never observed. Absolute CD4+ cell counts remained relatively stable, but NK cells fluctuated significantly over time and tended to correlate inversely with the virus titer in peripheral blood. Although only CD8+ T cells were directly demonstrated to exert a suppressive effect on viral replication in vitro, the observed fluctuation of NK cells suggests that these cells may also be involved in the interaction with lentivirus infection in this species.

Simian Immunodeficiency Virus Infection of Chimpanzees

“…Even in captive chimpanzees, only seven naturally infected individuals have been identified (17,24,51,63,64), and among these, only one (Noah) has been subjected to virological and immunological analyses (13,40,41,54,(56)(57)(58). Observational studies of both captive and wildliving apes seem to suggest that SIVcpz-infected chimpanzees do not become noticeably immunodeficient or succumb prematurely to opportunistic infections or neoplasms, although an obvious caveat here is that it is difficult in field studies to distinguish between these and other natural causes of death.…”

“…In this context, it is of interest that chimpanzee and human CD4 and CCR5 molecules differ at several potentially significant amino acid residues (15,85,96). In vivo, SIVcpz establishes a persistent infection and replicates to relatively high titers (10 4 to 10 5 viral RNA copies/ml) (58) but does not seem to be associated with CD4 cell decline or loss of CD4 cell function (40), increased apoptosis of CD4 ϩ T-lymphocytes (29), or extensive trapping of virus particles in germinal centers and degenerative changes in lymph node architecture (41). In this way, SIVcpz seems to resemble other nonpathogenic lentiviral infections, e.g., those of sooty mangabeys and African green monkeys (49,60,70,79), although an obvious caveat of these studies is that the in vivo chimpanzee data are derived from only a single naturally infected individual.…”

“…Of note, chimpanzees experimentally infected by HIV-1 are not equivalent to apes who acquired SIVcpz by natural routes. In most experimentally infected chimpanzees, HIV-1 replicates poorly, frequently at undetectable levels (40,53). Serial passage in chimpanzees can serve to increase this in vivo replication potential, but chimpanzee-adapted strains of HIV-1 cause CD4 T-cell decline and clinical AIDS, symptoms not observed in naturally infected apes (53,59).…”

“…What is also known but perhaps less widely appreciated is that SIVcpz strains have been transmitted to humans on at least three independent occasions and that the current HIV-1 group M pandemic, which has afflicted more than 60 million people and caused more than 20 million deaths, resulted from just one of these transmission events in the first half of the twentieth century (42,77,97). The reasons for HIV-1's sudden emergence, the adaptive changes that followed, and the mechanisms underlying its unique pathogenicity in humans have not yet been determined.Primates naturally infected with SIV, including SIVcpz-infected chimpanzees, appear not to develop immunodeficiency or AIDS (31,40,49,60,70,79). In contrast, HIV infection of humans is nearly always characterized by progressive loss of CD4 ϩ T lymphocytes, chronic immune activation, and gradual destruction of an array of immune functions (82).…”

“…Primates naturally infected with SIV, including SIVcpz-infected chimpanzees, appear not to develop immunodeficiency or AIDS (31,40,49,60,70,79). In contrast, HIV infection of humans is nearly always characterized by progressive loss of CD4 ϩ T lymphocytes, chronic immune activation, and gradual destruction of an array of immune functions (82).…”