In vitro correlates of HIV-2-mediated HIV-1 protection

A prospective study of high-risk commercial sex workers in Senegal has show n that HIV-2 infection may reduce the risk of subsequent HIV-1 infection; t hese findings have been confirmed and extended, now with 13 years of observ ation. While exploring the biological mechanisms behind this natural protec tion, we found that a significant proportion of peripheral blood mononuclea r cells obtained from HIV-2-infected subjects resisted in vitro challenge w ith CCR5-dependent HIV-1 viruses but not CXCR4-dependent viruses. High leve ls of beta-chemokines, the natural ligands of the CCR5 coreceptor, were cor related with low levels of viral replication, and resistance was abrogated by antibodies to beta-chemokines. Our results suggest that beta-chemokine-m ediated resistance may be an important correlate of HIV protection against HIV-1 infection and relevant to HIV vaccine design.