HIV infection--induced posttranslational modification of T cell signaling molecules associated with disease progression.

Journal Article

In attempt to elucidate the mechanism of the HIV infection induced T cell unresponsiveness, we studied signal-transducing molecules proximal to the T cell receptor (TCR) in T lymphocytes of HIV-infected individuals. Total amounts of protein tyrosine kinases (PTKs) Lck, Fyn, and ZAP-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 individuals in acute and early asymptomatic stages of HIV infection. Unexpectedly, 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 selectively T cells of HIV infected patients since B cell PTKs Syk and Lyn were detected structurally and functionally intact. Interestingly, similar alterations of signaling molecules were not detected in T cells of HIV-infected long-term asymptomatic individuals. Modification of T cell PTKs may thus underlie the HIV-induced impairment of lymphocyte function and may potentially predict disease progression.

Full Text

Duke Authors

Cited Authors

  • Stefanová, I; Saville, MW; Peters, C; Cleghorn, FR; Schwartz, D; Venzon, DJ; Weinhold, KJ; Jack, N; Bartholomew, C; Blattner, WA; Yarchoan, R; Bolen, JB; Horak, ID

Published Date

  • September 15, 1996

Published In

Volume / Issue

  • 98 / 6

Start / End Page

  • 1290 - 1297

PubMed ID

  • 8823293

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/JCI118915

Language

  • eng

Conference Location

  • United States