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. 1996 Sep 15;98(6):1290–1297. doi: 10.1172/JCI118915

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

I Stefanová 1, M W Saville 1, C Peters 1, F R Cleghorn 1, D Schwartz 1, D J Venzon 1, K J Weinhold 1, N Jack 1, C Bartholomew 1, W A Blattner 1, R Yarchoan 1, J B Bolen 1, I D Horak 1
PMCID: PMC507554  PMID: 8823293

Abstract

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.

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Selected References

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