Partial Resistance to Infection by R5X4 Primary HIV Type 1 Isolates in an Exposed-Uninfected Individual Homozygous for CCR5 32-Base Pair Deletion

Abstract

It is known that certain individuals remain persistently seronegative despite repeated exposure to HIV-1. Studies have shown that some exposed uninfected (EU) individuals who are homozygous for a 32-bp deletion in the CCR5 gene are resistant to infection with non-syncytium-inducing (R5) viruses. In the present investigation, we provide evidence that a highly exposed-uninfected individual with the CCR5 32-bp deletion (EU Delta 32-1) also has partial resistance to syncytium-inducing (R5X4) HIV-1 viruses, when compared with unexposed-uninfected individuals with (UU Delta 32-1 and UU Delta 32-2) and without (UU-1 and UU-2) the 32-bp deletion. The partial resistance of EU cells was due neither to altered coreceptor expression, nor to specific mutation or deletion in the coding region of chemokine coreceptors CXCR4 and CCR3. While SDF-1, the ligand for CXCR4, blocked entry of R5X4 viruses to a similar extent in EU Delta 32 and UU Delta 32, there was a differential production of soluble factors by EU Delta 32. Both CD4+ and CD8+ cells from EU Delta 32-1 produced soluble factors that efficiently suppressed infection by HIV-1 R5X4 viruses when compared with supernatant from UU Delta 32. These data provide evidence that additional soluble factors are involved in resistance to infection with R5X4 viruses.