Platelets Prevent IFN-alpha/beta-induced Lethal Hemorrhage Promoting CTL-dependent Clearance of Lymphocytic Choriomeningitis Virus

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2008 Jan 11

PMID 18184798

Citations 68

Authors

Matteo Iannacone

Giovanni Sitia

Masanori Isogawa

Jason K Whitmire

Patrizia Marchese

Francis V Chisari

Zaverio M Ruggeri

Luca G Guidotti

Affiliations

Soon will be listed here.

Abstract

We found that mice infected with different isolates of lymphocytic choriomeningitis virus (LCMV) develop a mild hemorrhagic anemia, which becomes severe and eventually lethal in animals depleted of platelets or lacking integrin beta3. Lethal hemorrhagic anemia is mediated by virus-induced IFN-alpha/beta that causes platelet dysfunction, mucocutaneous blood loss and suppression of erythropoiesis. In addition to the life-threatening hemorrhagic anemia, platelet-depleted mice fail to mount an efficient cytotoxic T lymphocyte (CTL) response and cannot clear LCMV. Transfusion of functional platelets into these animals reduces hemorrhage, prevents death and restores CTL-induced viral clearance in a manner partially dependent on CD40 ligand (CD40L). These results indicate that, upon activation, platelets expressing integrin beta3 and CD40L are required for protecting the host against the induction of an IFN-alpha/beta-dependent lethal hemorrhagic diathesis and for clearing LCMV infection through CTLs.

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