Simian Immunodeficiency Virus Infection of Chimpanzees

Abstract

Simian immunodeficiency viruses (SIVs) are primate lentiviruses that infect no fewer than 36 different nonhuman primate species in sub-Saharan Africa (4,9,62). Two of these viruses, SIVcpz from chimpanzees (Pan troglodytes) and SIVsmm from sooty mangabeys (Cercocebus atys), have crossed species barriers on multiple occasions and have generated human immunodeficiency virus (HIV) types 1 and 2 (20,24,25,94). AIDS, one of the most devastating infectious diseases to have emerged in recent history, is thus the result of cross-species infections of humans by lentiviruses of primate origin (33).Identification of the primate source that spawned the HIV-1 pandemic is of scientific and public health importance. To this end, it is now well established that the immediate precursor of HIV-1 is a lentivirus that infects chimpanzees of the subspecies Pan troglodytes troglodytes in west central Africa (17,24). 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). The basis for this difference in pathogenicity is not understood, but deciphering which viral and/or host factors are responsible for the nonpathogenic course of natural SIV infections could well prove useful in developing more-effective treatment or prevention strategies for HIV/AIDS.Chimpanzees and humans share more than 98% sequence identity across their genomes (91). This degree of relatedness provides a unique opportunity to search for key differences in virus-host interactions responsible for differences in viral pathogenicity, an approach that could prove complementary to current studies that focus primarily on human disease susceptibility (55). In this review, we summarize recent progress in four key scientific areas related to AIDS pathogenesis: (i) the origin of HIV-1; (ii) the origin of SIVcpz; (iii) natural SIVcpz reservoirs; and (iv) the natural history of SIVcpz infection. Scientific and public health implications of these data as they relate to human infections by the corresponding virus, HIV-1, will also be discussed.

Evolution of human-chimpanzee differences in malaria susceptibility: Relationship to human genetic loss of N -glycolylneuraminic acid

“…Meanwhile, there is substantial evidence that multiple subspecies of chimpanzees may have been separated Ͼ1 mya (16,17). It is interesting to note that there is other evidence of distinct pathogen regimes for each of these subspecies, including hepatitis B (59) and HIV (60,61).…”

The spread, treatment, and prevention of HIV-1: evolution of a global pandemic

“…HIV-1 is thought to have arisen from cross-species transmission of a chimpanzee virus to humans (5,6) and HIV-2 from cross-species transmission of a Sooty mangabey virus (7). Three groups of HIV-1 have been described, labeled M, N, and O, based on genome differences.…”

HIV Without AIDS: The Immunological Secrets of Natural Hosts

“…While searching for the age and origins of the chimpanzee SIV, a major breakthrough came when it was noticed that the 5' region of the chimpanzee SIV genome closely matches that found in red-capped mangabeys (Cercocebus torquatus), but the 3' end closely resembles SIVs found in greater spot-nosed (Cercopithecus nictitans), mustached (Cercopithecus cephus) and mona monkeys (Cercopithecus mona). Based on these findings, SIV cpz is thought to be a recombination of viruses ancestral to those found in red-capped mangabeys, mona, spot-nosed and mustached monkeys (Paul M Sharp, Shaw, & Beatrice H Hahn, 2005). The data suggest that chimpanzees have not evolved along with their own SIV for very long, and may represent a necessary evolutionary stage for the virus to enable cross-species transmission into humans.…”