HIV-1 Tat-induced Platelet Activation and Release of CD154 Contribute to HIV-1-associated Autoimmune Thrombocytopenia

Overview

Journal J Thromb Haemost

Publisher Elsevier

Specialty Hematology

Date 2010 Dec 15

PMID 21143381

Citations 27

Authors

J Wang

W Zhang

M A Nardi

Z Li

Affiliations

Soon will be listed here.

Abstract

Background: Enhanced platelet activation in human immunodeficiency virus (HIV)-1-infected patients has been reported and shown to strongly correlate with plasma viral load. Activated platelets are known to express and to release a variety of proteins that can modulate the immune system. Specifically, platelet-derived CD154 has been shown to be directly involved in the development of autoimmune thrombocytopenia (ITP). The mechanism by which HIV-1 infection leads to platelet activation and the effect of this activation on the development of HIV-1 ITP, however, is not fully understood.

Objective: We have investigated the effect of HIV-1 Trans activating factor (Tat) on platelet activation.

Results: We report that HIV-1 Tat directly interacts with platelets and induces platelet activation resulting in platelet micro-particle release. This activation by Tat requires the chemokine receptor CCR3 and β3-integrin expression on platelets, as well as calcium flux. Tat-induced activation of platelets releases platelet CD154, an immune modulator. Enhanced B-cell activity is found in mouse spleen B cells co-cultured with platelets treated with Tat in vitro. An early antibody response against adenovirus is found in Tat-injected mouse immunized with adenovirus, suggesting an enhanced immune response in vivo.

Conclusions: We have described a role of Tat-induced platelet activation in the modulation of the immune system, with implications for the development of HIV-1-associated thrombocytopenia.

Citing Articles

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