Reduced HIV-1 infectability of CD4+ lymphocytes from exposed-uninfected individuals:: Association with low expression of CCR5 and high production of β-chemokines

We examined the human immunodeficiency virus type 1 infectability of CD4(+) lymphocytes isolated from CCR5 wild-type individuals, individuals heterozygous for the Delta 32 allele of CCR5, and HIV-l-exposed but uninfected (EU) individuals who had CD4(+) lymphocytes refractory to M-tropic viral replication. None of the EU individuals were found to be heterozygous for the Delta 32 allele. The CD4(+) lymphocytes isolated from CCR5/Delta 32 and EU individuals were less infectable with an M-tropic viral isolate of HIV-1 than CCR5/CCR5 control individuals but were equally as infectable with a T-tropic viral isolate. The restriction to M-tropic viral isolate replication did not associate with any profound genotypic change in the CCR5 gene. CD4(+) lymphocytes from CCR5/Delta 32 and CCR5/CCR5 EU individuals were more sensitive to the HIV-inhibitory effects of the recombinant beta-chemokines RANTES, MIP-1 alpha, and MIP-1 beta than were CD4(+) lymphocytes from CCR5/CCR5 control individuals. CD4(+) lymphocytes from EU individuals also showed increased sensitivity to recombinant beta-chemokines and low surface expression of CCR5. A phenotype of low CCR5 expression and high secretion of beta-chemokines is associated with reduced infectability of cells by M-tropic HIV-1. This phenotype may also be associated with protection against sexual transmission of HIV-1. (C) 1998 Academic Press.