Polymorphism in the interleukin-4 promoter affects acquisition of human immunodeficiency virus type 1 syncytium-inducing phenotype

The emergence of syncytium-inducing (SI) variants of human immunodeficiency virus type 1 (HIV-1) in infected individuals is an indicator of poor progn osis and is often correlated with faster CD4(+) cell depletion and rapid di sease progression. Interleukin-4 (IL-4) is a pleiotropic cytokine with vari ous immune-modulating functions including induction of immunoglobulin E (Ig E) production in B cells, down-regulation of CCR5 (a coreceptor for HIV-1 n on-SI [NSI] strains), and up-regulation of CXCR4 (a coreceptor for HIV 1 SI variants). Here we show that homozygosity of a polymorphism in the IL-4 pr omoter region, IL-4-589T, is correlated with increased rates of SI variant acquisition in HIV-1-infected individuals in Japan. This mutation was also shown to be associated with elevated serum IgE levels in HIV-1-infected ind ividuals, especially in those at advanced stages of disease. In contrast, n either a triallele polymorphism in IL-10, another Th2 cytokine, nor a biall ele polymorphism in the RANTES promoter affected acquisition of the SI phen otype, This finding suggested that IL-4-589T increases IL-4 production in t he human body and thus accelerates the phenotypic switch of HIV-1 from NSI to SI and possibly disease progression of AIDS.