Despite considerable research, the mechanisms by which HIV disrupts thymic
function remain controversial. We have described the phenotypic changes tha
t occur in the thymus of SIV-infected macaques during acute SIV infection,
In this study, we analyzed the effects of SIV infection on apoptotic pathwa
ys in thymic tissue from newborn macaques infected with SIV, Thymocyte apop
tosis was accompanied by a modest increase in surface Fas expression, a pro
found decrease in the frequency of bcl-2-positive cells, as well as the amo
unt of bcl-2 per cell. With control of viral replication, levels of bcl-2 a
nd Fas returned to baseline together with a return to basal levels of apopt
osis, In the thymus, SIV infection resulted in depletion of CD4(+)CD8(+) th
ymocytes, an increase in apoptosis of thymocytes, and a down-regulation of
MHC class I molecules, These changes peaked 14-21 days after infection at o
r just after peak viremia, This data further suggests disruption of the ant
iapoptotic pathway regulated by bcl-2 plays a critical role in SIV-induced
apoptosis of thymocytes.