Interactions between major histocompatibility complex class II surface expression and HIV: implications for pathogenesis

Abstract

Although it has been almost 20 years since the first cases of acquired immunodeficiency syndrome (AIDS) were documented, the pathogenesis is still not completely understood. Interactions between major histocompatibility complex (MHC) Class I and human immunodeficiency virus (HIV), resulting in down-regulation of MHC-I surface expression, have been reported to contribute to pathogenesis by suppressing the host's immune response. Interactions between MHC Class II and HIV have also been described, but it is unclear how these contribute to the pathogenesis. MHC-II surface expression on HIVinfected monocytes and monocytic cell lines has been described to be increased as well as decreased when compared to uninfected control monocytes. HIV-specific mechanisms appear to down-regulate MHC-II expression on blood monocytes during HIV-1 infection, whereas host mechanisms up-regulate MHC-II expression in response to infection of blood monocytes as well as brain macrophages. A balance between these two may determine MHC-II expression levels in individual patients.Altogether, HIV seems to be able to benefit from both low and high levels of MHC-II surface expression. The first results in reduced immune surveillance of the host, allowing the virus to replicate faster; the second increases infectivity of the virus as a result of higher MHC-II density on macrophages and virion particles.

Expansion of a subset of CD14highCD16negCCR2low/neg monocytes functionally similar to myeloid-derived suppressor cells during SIV and HIV infection

“…We hypothesize that the discrepancy between these subpopulations may simply reflect the variable ratios by which classical monocytes differentiate into other phenotypes [12], such as inflammatory tissue macro-phages, DCs, intermediate monocytes, and the CCR2 low/neg subset, under inflammatory conditions. In addition, SIV-and HIV-infected monocytes are reported to undergo phenotypic changes, including apoptosis, modulation of MHC proteins, and even up-regulation of surface CCR2 expression [43,65,66], which could also interfere with differentiation and trafficking.…”

Immune Regulation and Evasion of Mammalian Host Cell Immunity During Viral Infection

“…Moreover, MHC-II expression in HIV-1 infection has been studied in primary monocytes and monocytic cell lines, which reveals that downregulation of MHC-II expression contributes to pathogenesis by allowing virus to replicate faster. At the same time, upregulation of MHC-II may also enhance infectivity mediated by high density of MHC-II on macrophages and increased number of virions in a dynamic immunoregulatory response [72]. HIV-1 infection has also been found to upregulate MHC-II expression in T and B cell lines, macrophages and peripheral blood mononuclear cells (PBMC) without significantly altering CD80/86 expression [42].…”

Characterization and Role of Lentivirus-Associated Host Proteins

“…The second molecule specific for CD4-MHC II-is enriched on the surface of the virus, which may help to explain the well-documented "preference" of HIV to infect CD4+ cells because the presence of MHC II on the virion surface has been shown to increase virion-target cell interaction and binding and, subsequently, to increase viral infectivity of MHC II-positive virions as compared with those that are MHC II negative (68,69). Similarly, the rate of MHC II incorporation into the virion envelope has been shown to increase with an increase in the expression of the protein on the host cell (26), Because HIV infection upregulates the expression of MHC II on the surface of infected cells (87) and that MHC II-positive HIV virions are more infectious, this may represent a "self-amplifying loop" by which the virus population increases its infectivity.…”