Following the discovery of HIV-1 as the cause of epidemic AIDS in the United States, Europe, and Asia, patients in West Africa with AIDS-like symptoms were identified whose sera reacted more strongly with an immunodeficiency virus (SIV_MAC ) isolated from captive rhesus macaques in US primate centers than with HIV-1. The identification of patients with serologic reactivity for SIVMAC raised the possibility that certain African human and simian populations could be infected with immunodeficiency viruses related to but distinct from HIV-1. An extensive survey of African primate species for such viruses led to the identification of distinct SIV viruses in African green monkeys (SIV_AGM ), mandrills (SIV_MND ), sooty mangabeys (SIV_SM ), and chimpanzees (SIV_CPZ ).

West African patients with AIDS-like symptoms and healthy individuals at risk for AIDS were identified who were infected with a virus closely related to SIVSM . This virus was isolated, molecularly cloned and characterized, and shown to represent a second major class of human immunodeficiency viruses termed HIV-2.

Although originally limited geographically to West Africa, HIV-2 has now been identified in patients in Europe, the United States, South America, and India. HIV-2 is approximately 40 to 50% similar to HIV-1 in overall nucleotide sequence homology.

There are two major differences in the genomic organization of HIV-1 and HIV-2. The vpu gene of HIV-1 is not present in HIV-2, and HIV-2 contains an additional gene, vpx, in a central region that is not present in HIV-1. Although the function of vpx is not entirely clear, it is packaged in the viral particle, like vpr, and it may have a similar function related to nuclear transport or processing of the viral preintegration complex. Antigenically, HIV-2 and HIV-1 are distinct, with greatest cross reactivity in structural proteins and least in envelope proteins. Currently licensed ELISA tests to detect HIV-1 infection generally include HIV-2 antigens.

However, confirmation requires specific testing by Western immunoblot using HIV-2-specific proteins as antigen. Like HIV-1, HIV-2 selectively infects CD4+ cells. Although HIV-2 can cause profound immunodeficiency and an AIDS syndrome indistinguishable from that caused by HIV-1, evidence suggests that HIV-2 may in general be less virulent than HIV-1 and cause disease over a more prolonged period of time.

The discovery of two distinct types of human immunodeficiency viruses (HIV-1 and HIV-2) having closely related counterparts in African primates (SIVCPZ chimpanzees and SIVSM in wild-caught sooty mangabeys, respectively), along with epidemiologic findings revealing Africa as the geographic source of all human and SIVs, suggest cross-species (zoonotic) infection for the origin of HIV-1 and HIV-2. This conclusion is strengthened by a molecular phylogenetic analysis of the genomes of all known primate lentiviruses. This figure indicates that HIV-1 and HIV-2 are members of a much larger group of lentiviruses that infect a number of different primate species in the wild. It is apparent that the closest phylogenetic relative of HIV-1 is SIV_CPZ , and for HIV-2, is SIV_SM . Nevertheless, it is premature to conclude that the chimpanzee and sooty mangabey are the proximal hosts for the human viruses because other primate species in Africa remain to be evaluated and could also serve as natural reservoirs. Such studies are fundamentally important to the elucidation of the origin of the current AIDS epidemic, the molecular basis for the pathogenicity of HIVs and SIVs in natural and unnatural host species, and an explanation for the relatively recent appearance of AIDS as an epidemic.

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