Resistance against syncytium-inducing human immunodeficiency virus type 1 (HIV-1) in selected CD4(+) T cells from an HIV-1-infected nonprogressor: Evidence of a novel pathway of resistance mediated by a soluble factor(s) that acts after virus entry

A panel of CD4(+) T-cell clones were generated from peripheral blood lympho cytes from a patient with a nonprogressing infection of human immunodeficie ncy virus type 1 (HIV-1) by using herpesvirus saimiri as described recently . By and large, all of the clones expressed an activated T-cell phenotype ( Th class 1) and grew without any further stimulation in interleukin-2-conta ining medium. None of these clones produced HIV-1, and all clones were nega tive for HIV-1 DNA. When these clones were infected with primary and labora tory (IIIB) strains of HIV-1 with syncytium-inducing (SI) phenotypes, drama tic variation of virus production was observed. While two clones were highl y susceptible, other clones were relatively or completely resistant to infe ction with SI viruses. The HIV-resistant clones expressed CXCR4 coreceptors and were able to fuse efficiently with SI virus env-expressing cells, indi cating that no black to virus entry was present in the resistant clones. Ad ditionally, HIV-1 DNA was detectable after infection of the resistant clone s, further suggesting that HIV resistance occurred in these clones after vi rus entry and probably after integration. We further demonstrate that the r esistant clones secrete a factor(s) that can inhibit SI virus production fr om other infected cells and from a chronically infected producer cell line. Finally, we show that the resistant clones do not express an increased amo unt of ligands (stromal-derived factor SDF-1) of CXCR4 or other known HIV-i nhibitory cytokines. Until now, the ligands of HIV coreceptors were the onl y natural substances that had been shown to play antiviral roles of any rea l significance in vivo. Our data from this study show that differential exp ression of another anti-HIV factor(s) by selected CD4(+) T cells may be res ponsible for the protection of these cells against SI viruses. Our results also suggest a novel mechanism of inhibition of SI viruses that acts at a s tage after virus entry.