Received 6/18/97, Accepted 7/22/97

Although most of our attention is focused on HIV-1, there are several interesting aspects of molecular immunity which could be learned from the related SIV lentivirus. The various SIVs are the most-closely-related viruses, some of these strains cause AIDS-like diseases in various species of primate. But there are a number of seemingly anomalous host-virus interactions, and these each give clues to how primates deal with lentiviral infection.

For example, nearly 50% of African green monkeys are infected with a sub-strain of SlVagm in the wild, yet no clinical pathology has been associated to date (reviewed in 96). Similarly, sooty mangabeys have been shown—both in the wild and in breeding colonies—to be infected with a sub-strain of SIVsm (96-99). Like the African-green-monkey infection, the sooty-mangabey infection appears to cause no disease in its native host, even though SlVagm and SIVsm are both known to cause AIDS-like disease in other species of monkey. Somehow, these monkeys have developed a means of controlling these retroviruses. In fact, in the breeding colony of sooty mangabeys where the original SlVsm isolate was discovered, as many as 80% of the animals were infected—some for over a decade—without manifesting any evidence of disease (100). Also, there is a striking homology between SIVsm of sooty mangabeys and HIV-2 (100). and there is correspondingly significant sequence homology between HIV-1 and a simian immunodeficiency virus, SIVcpz, which was originally isolated from chimpanzees, who were without evidence of disease (101-102). Of particular note, chimpanzees experimentally infected with HIV-1, fail to develop overt disease despite establishment of infection as evidenced by transient viremia, (103-104), and development of HIV-1 specific antibodies (105) and HIV-1 specific cytotoxic T-cells (106-107). These observations strongly suggest that these primates already have a molecular immunity to these lentiviruses. The question is that why exposure of these SIV-strains , which are non-pathogenic in one species of primates, becomes pathogenic when other species of primates are exposed to them.

In humans, this complex pattern of varying pathogenecity among lentiviruses is also manifested in the clinical expression of other retroviruses. For example, the "human foamy virus (HFV)" or spumaviruses infects humans but has not been associated with any known disease. This lack of clinical expression persists despite a high prevalence of infection among certain human populations, and infectious virus can be readily cultured from the infected tissue specimens from these individuals (108-109).

Human T -cell lukemia virus (HTLV)-II has been shown to be endemic in certain native American Indians without any manifestation of clinical disease (110). In contrast, infection with the similar HTLV-I in a minority of individuals leads to either adult T-cell leukemia if acquired in infancy, or a chronic neuropathic disease if acquired late in life (110). Despite many similarities among these retroviruses, there are marked differences in the level of clinical expression. Yet, it is apparent by the maintenance of infectious disease processes within these populations that low level of virions are being produced from the integrated proviral sequences.

Similarly, although less dramatic, substantial disease variability has been observed with the clinical course of HIV-1 infection. For example, about 5% of HIV-1-infected individuals are long term non-progressor (LTNP) for as long as 15 years (1-4, 80-82, 88). In contrast, other reports document patients who rapidly progress to immunodeficiency in a matter of a few years (30). Furthermore, when one compares HIV-1 with HIV-2, there is a marked difference in the clinical course, with the HIV-2 infection being significantly prolonged (30). The prior example regarding documented exposure of >2,000 health care workers is most curious, as only 4 have seroconverted and none has developed AIDS (10-12). And then there are the cases of spontaneous clearance of HIV-1 (84-86), or lack of transmission of HIV-1 in individuals who have multiple unprotected sexual contacts with HIV-1-infected partner, even though HIV-1 is present in almost 80-100% of human semen specimens (80-82). Other anomalous observations are the reported isolation of HIV-1 from individuals who remained HIV-1-seronegative, and the observation that some men with many different partners with whom they practiced receptive anal sex still remain seronegative (1-2).