A Tumor Necrosis Factor--α--Inducible Promoter Variant of Interferon-ϒ Accelerates CD4 + T Cell Depletion in Human Immunodeficiency Virus--1--Infected Individuals.

A polymorphism, 3179G/T, in the promoter of the interferon (IFN)-γ gene (IFNG) confers differential tumor necrosis factor-α (TNF-α) inducibility to the IFNG promoter. The rarer allele, 3179T, but not 3179G, is inducible by TNF-α. We investigated the effects of IFNG 3179G/T on AIDS pathogenesis. In 298 African American human immunodeficiency virus (HIV)-1 seroconverters, the IFNG 3179G/T genotype was associated with accelerated progression to CD4<200 and AIDS-1993, a finding suggesting that IFNG 3179T is a risk factor for AIDS progression, as measured by CD4 cell count. It is possible that increased IFN-γ production induced by TNF-α when 3179T is present causes CD4 cell depletion by apoptosis. [ABSTRACT FROM AUTHOR]