Scientific Publications by FDA Staff

AIDS Res Hum Retroviruses 2004 May;20(5):507-12

HIV Type 2 Primary Isolates Induce a Lower Degree of Apoptosis "in Vitro" Compared with HIV Type 1 Primary Isolates.

Machuca A, Ding L, Taffs R, Lee S, Wood O, Hu J, Hewlett I

Hewlett I, US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, HFM 315,1401 Rockville Pike, Rockville, MD 20852 USA US FDA, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, Off Blood Review & Res,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA US FDA, Lab Bacterial Parasit & Unconvent Agents, Div Emerging & Transfus Transmitted Dis, Off Blood Review & Res,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA

To determine whether subtypes of HIV-1 and HIV-2 vary in their ability to induce T cell apoptosis in vitro, human peripheral blood mononuclear cells (PBMC) from healthy donors and CEM.NKR-CCR5 cells were infected with a variety of HIV-1 and HIV-2 isolates in vitro. Apoptotic cell levels and chemokine and cytokine production were analyzed. Significant variations in cytopathic effects following in vitro infection with primary isolates of HIV-1 or HIV-2 subtypes were observed in PBMCs. The percent of apoptotic cells from each individual ranged from 2 to 78% after HIV-1 infection and from 0 to 28% after HIV-2 infection (p < 0.01). We did not observe significant differences in the degree of apoptosis induced among cells infected with different HIV-1 group M subtypes or group O virus, nor among cells infected with different HIV-2 isolates. However, HIV-2 induced significantly lower degree of apoptosis overall in PBMC and CEM.NKR-CC5 cells when compared with HIV-1 subtypes (p < 0.0001). No significant differences were observed in the production of chemokines, such as RANTES, MIP-1alpha, and MIP-1beta, and cytokines, such as TNF-alpha and TNF-beta when PBMC cultures were infected with different HIV-1 subtype viruses, or HIV-2 isolates. In conclusion, HIV-2 isolates induced significantly lower levels of T cell apoptosis in both PBMC and CEM.NKR-CCR5 cells than HIV-1 isolates. No differences in T cell apoptosis levels were seen between different subtypes of HIV-1 group M or group O isolates. This is consistent with the mild clinical course of infection with HIV-2 that has been reported relative to that observed with HIV-1.