Induction of apoptosis by primary HIV-1 isolates correlates with productive infection in peripheral blood mononuclear cells.

Abstract

To study the apoptosis-inducing capacity of HIV-1 primary isolates in human peripheral blood mononuclear cells (PBMC) in relation to the viral biological phenotype. Four HIV-1 primary 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 apoptosis induction in PBMC as determined by intracellular labelling of apoptotic DNA strand breaks and flow cytometry analysis. When low virus dose was used (0.001 m.o.i.), productive virus infection, with 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 production with peak RT activity at day 3 followed by high numbers of apoptotic cells at day 5 after infection. The apoptosis-inducing capacity of virus isolates was independent of their capacity to induce syncytia or replicate in the MT-2 cell line. However, upon cocultivation of infected PBMC with MT-2 cells, only virus with the MT-2 tropic phenotype initiated productive infection and induced apoptosis in MT-2 cells. These results show that apoptosis induction in PBMC by primary HIV-1 isolates is closely related to the kinetics of virus replication but is not influenced by other biological properties of the virus such as syncytium-inducing capacity and MT-2 tropism.