A Tumor Necrosis Factor–a–Inducible Promoter Variant of Interferon-g Accelerates CD4+ T Cell

A polymorphism,179G/T, in the promoter of the interferon (IFN)–g gene (IFNG) confers differential tumor necrosis fac-tor-a (TNF-a) inducibility to the IFNG promoter. The rarer allele, 179T, but not 179G, is inducible by TNF-a. We investigated the effects of IFNG 179G/T on AIDS patho-genesis. In 298 African American human immunodeficiency virus (HIV)–1 seroconverters, the IFNG 179G/T genotype was associated with accelerated progression to CD4!200 and AIDS-1993, a finding suggesting that IFNG 179T is a risk factor for AIDS progression, as measured by CD4 cell count. It is possible that increased IFN-g production induced by TNF-a when 179T is present causes CD4 cell depletion by apoptosis. Host genetic factors have been shown to influence both the risk of human immunodeficiency virus (HIV)–1 transmission and the rate of HIV-1 disease progression. In particular, poly-morphisms in the genes for HIV-1 coreceptors and for their natural ligands have been shown to modify both HIV-1 trans