The role of the immune response during SIVagm infection of the african green monkey natural host

Abstract

The African green monkey (AGM) is one of many African species endemically infected with simian immunodeficiency virus (SIV). Like the other natural hosts, AGMs do not succumb to AIDS and understanding the basis for this resistance to disease progression would be of enormous theoretical and practical importance. Early efforts by our group that concentrated on identifying immune mechanisms presumed to keep the virus under control failed to find any obvious candidates. The presumption of virus control was invalidated by the finding that SIVagm replicates in AGMs with the same vigor as HIV-1 does in humans. Focus therefore shifted to identifying possible immunopathologic features present in disease susceptible hosts but absent in the AGM natural host. The apparent immunologic tolerance of AGMs to the SIVagm core protein led to the development of a hypothesis implicating anti-Gag antibodies in the formation of immune complexes, virus trapping in the lymph nodes and immune dysfunction. The idea proved difficult to test in vivo and present work focuses on the possibility that Gag tolerance at the T-cell level plays an important role in preventing the catastrophic demise of the immune system characteristic of immunodeficiency virus infection of the heterologous primate host.

Human Immunodeficiency Virus Proteins Mimic Human T Cell Receptors Inducing Cross-Reactive Antibodies

“…These results are also consistent with HIV being closely related to class K human endogenous retroviruses [ 63 , 64 , 65 , 66 , 67 , 68 , 69 ]. Additionally, this hypothesis is also consistent with SIV being non-pathogenic in some monkey species due a T-cell-mediated mechanism [ 59 , 60 ]. In short, HIV may have evolved, or is in the process of evolving, into a commensal organism that is only pathogenic under extraordinary conditions of immunological dysfunction.…”

“…To summarize the experimental results, HIV mimics human TCR at a far higher rate than any other microbe thus far examined. In context, this finding strongly suggests that if HIV is not already a commensal organism for human beings, it is well on its way, just as simian immunodeficiency virus (SIV) is commensal for some monkey species [ 59 , 60 ]. The support for this conclusion is that previous research has demonstrated that the more similarities a microbe has to the TCR repertoire of a host organism, the greater the probability is that this microbe is a commensal organism or symbiont for its host [ 3 , 4 , 5 , 6 , 7 ].…”

Inhibition of Adaptive Immune Responses Leads to a Fatal Clinical Outcome in SIV-Infected Pigtailed Macaques but Not Vervet African Green Monkeys

“…These differences suggest that natural hosts may have developed a complex arsenal of protective mechanisms to cope with the pathogenic consequences of SIV-infection. Adaptive immune responses, such as SIV-specific CD8+ T cells and humoral immune responses, have also been observed in SIV-infected natural hosts either at comparable or lower magnitude than in pathogenic SIV and HIV infection [18],[19],[20],[21],[22],[23],[24]. However, the ultimate role of adaptive immune responses in the protection against disease progression in AGM and other natural hosts of SIV remain elusive.…”