Role of apoptosis induction in both peripheral lymph nodes and thymus in progressive loss of CD4(+) cells in SHIV-infected macaques

To investigate the role of apoptosis in the progressive loss of CD4(+) lymp hocytes in HIV infection, we have used macaques infected with SHIV, a hybri d virus of HIV and simian immunodeficiency virus (SIV), In the present stud y, we sequentially analyzed apoptosis induction in the acute phase of SHIV infection. Four macaques infected with a pathogenic SHIV, SHIV89.6P, and fo ur macaques infected with a nonpathogenic SHIV, NM-3rN, were analyzed durin g the first 2 or 4 weeks postinfection, In the 89.6P-infected macaques the number of peripheral CD4(+) cells sharply decreased at 2 weeks postinfectio n and was maintained below 50/mu l until 4 weeks postinfection, while in th e NM-3rN-infected macques the number of the CD4(+) cells did not change sig nificantly. Plasma viral loads peaked at 2 and 2-3 weeks postinfection, and the peak values were about 1 x 10(9) and 10(6)-10(7) copies/ml in the 89.6 P- and the NM-3rN-infected macaques, respectively. In the 89.6P-infected ma caques, Fas antigen expression and the extent of apoptosis in PBMCs and per ipheral lymph nodes increased at 1-2 weeks postinfection, A high number of apoptotic cells was also observed in thymus sections 2 and 4 weeks postinfe ction, On the other hand, apoptosis was scarcely induced in the NM-3rN-infe cted macaques, These results suggest that the extent of apoptosis induction is closely correlated with the pathogenicity of SHIV and that the apoptosi s induction in peripheral lymphoid tissues and thymus, where T cell maturat ion occurs, may play an important role in the depletion of CD4(+) lymphocyt es in 89.6P infection.