INDUCTION OF APOPTOSIS BY PRIMARY HIV-1 ISOLATES CORRELATES WITH PRODUCTIVE INFECTION IN PERIPHERAL-BLOOD MONONUCLEAR-CELLS

Objective: To study the apoptosis-inducing capacity of HIV-1 primary i solates in human peripheral blood mononuclear cells (PBMC) in relation to the viral biological phenotype. Design and methods: Four HIV-1 pri mary isolates capable of replicating and inducing syncytia in the MT-2 cell line and two primary isolates lacking these properties were used to infect PBMC with the same infectious doses. The kinetics of virus production in the culture supernatants were followed in relation to ap optosis induction in PBMC as determined by intracellular labelling of apoptotic DNA strand breaks and flow cytometry analysis. Results: When low virus dose was used (0.001 m.o.i.), productive virus infection, w ith peak reverse transcriptase (RT) activity at days 5-7, was followed by high numbers of apoptotic cells at day 10 post infection. Tenfold higher inoculum dose (0.01 m.o.i.) resulted in enhanced virus producti on with peak RT activity at day 3 followed by high numbers of apoptoti c cells at day 5 after infection. The apoplosis-inducing capacity of v irus isolates was independent of their capacity to induce syncytia or replicate in the MT-2 cell line. However, upon cocultivation of infect ed PBMC with MT-2 cells, only virus with the MT-2 tropic phenotype ini tiated productive infection and induced apoptosis in MT-2 cells. Concl usions: These results show that apoptosis induction in PBMC by primary HIV-1 isolates is closely related to the kinetics of virus replicatio n but is not influenced by other biological properties of the virus su ch as syncytium-inducing capacity and MT-2 tropism.