HIV INFECTION-INDUCED POSTTRANSLATIONAL MODIFICATION OF T-CELL SIGNALING MOLECULES ASSOCIATED WITH DISEASE PROGRESSION

In attempt to elucidate the mechanism of the HIV infection induced T c ell unresponsiveness, we studied signal-transducing molecules proximal to the T cell receptor (TCR) in T lymphocytes of HIV-infected individ uals, Total amounts of protein tyrosine kinases (PTKs) Lck, Fyn, and Z AP-70 and the zeta chain of the TCR were found significantly decreased in T cells of symptomatic/AIDS patients as well as in T cells of indi viduals in acute and early asymptomatic stages of HIV infection, Unexp ectedly, the detection of Lck, Fyn, and ZAP-70 was reversed after the treatment of cell lysates with dithiothreitol, This suggests that PTKs Lck, Fyn, and ZAP-70 were modified by a mechanism altering the status of sulfhydryl groups, Moreover, this mechanism seems to affect select ively T cells of HIV infected patients since B cell PTKs Syk and Lyn w ere detected structurally and functionally intact, Interestingly, simi lar alterations of signaling molecules were not detected in T cells of HIV-infected long-term asymptomatic individuals, Modification of T ce ll PTKs may thus underlie the HIV-induced impairment of lymphocyte fun ction and may potentially predict disease progression.