Resistance to Human Immunodeficiency Virus 1 Infection Conferred by a Compound CCR5Δ32 and CCR5 C20S Heterozygote

Abstract

We analyzed same-gender couples discordant in their HIV status. The HIV+ partner was homozygous for CCR5 while his receptive HIV- partner was a CCR5Δ32 heterozygote with a C20S missense mutation in his CCR5 allele. The cells from the HIV- partner showed significant resistance to R5 fusion/infection and had no chemotactic response to CCL4 (MIP-1β). We demonstrated abundant CCR5-specific RNA in the HIV- partner’s cells but no detectable CCR5 protein. CCR5 promoter region cloned from each partner’s DNA indicated no significant impact on RNA transcription. The compound effect of CCR5Δ32 and C20S mutation impaired CCR5 coreceptor function and conferred resistance to HIV-1.

Immune Responses to the human retroviruses HIV-1 and HTLV-1

“…This strategy, however, is limited by the number of donors who are homozygous for the CCR5∆32 allele (Reviewed in 4). Recent studies reported resistance to HIV-1 infection in a CCR5∆32 heterozygote [4]. The study proposed that the higher percent of resistant CCR5∆32 heterozygotes might provide higher number of donors for stem cell transplantation.…”