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

Authors

Bashar Alkhatib
Mary Jabari
Shymaa Bilasy
Husni Abdul-Rahman
Kamal Sandhu
Stephen Lai
Ghalib Alkhatib

Publication Date

7-14-2023

Journal

The Journal of Infectious Disease

Abstract

We analyzed findings in a same-gender couple discordant in their human immunodeficiency virus (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 (macrophage inflammatory protein 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.

Keywords

HIV Infections, Humans, Disease Resistance, HIV-1, Receptors, CCR5, Male, Mutation, Missense, CCR5, CCR5Δ32, HIV/AIDS, heterozygous, homozygous

Comments

Supplementary Materials

PMID: 36912158