The human uniqueness of HIV: innate immunity and the viral Tat protein

Abstract

We have previously reported, and confirm here, that the human innate system of natural antibodies includes two, each of which is reactive, presumably by happenstance, with a specific sequence of HIV Tat protein. Comparison of cohorts of HIV+ and normal (HIV-) sera indicate that, following a period of post-infection latency, the titers of those natural antibodies decline and other Tat reactive antibodies, as evidence of induced immune response, do not arise. That human-typical pattern of innate/adaptive reactivity with HIV Tat protein is shared by chimpanzees, but not by other mammals tested in this study, in which those natural antibodies are not present, and apparently induced Tat-reactive antibodies do arise. Evidence of a temporal relationship between the decline of the Tat reactive natural antibodies and progression of HIV pathogenesis, including demise of CD4+T cells, suggests a role for those antibodies in retardation of that pathoprogression. However, that providential arrest of Tat-related pathogenicity may be limited by the immune system recognition of the natural antibody-reactive sequences of Tat as "self" with consequent induction of tolerance and restriction of production of those antibodies. The limited occurrence of progression to AIDS in chimpanzees may reflect an additional innate characteristic, one of resistance to tolerance-based diminishment of the protective natural antibodies. Although not yet defined, that characteristic may be shared by the occasionally observed HIV+ humans known as LTNP (longterm-non-progressors).