Yj. Zhang et al., INDUCTION OF APOPTOSIS BY PRIMARY HIV-1 ISOLATES CORRELATES WITH PRODUCTIVE INFECTION IN PERIPHERAL-BLOOD MONONUCLEAR-CELLS, AIDS, 11(10), 1997, pp. 1219-1225
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.