Platelets prevent IFN-alpha/beta-induced lethal hemorrhage promoting CTL-dependent clearance of lymphocytic choriomeningitis virus

Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):629-34. doi: 10.1073/pnas.0711200105. Epub 2008 Jan 9.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blood Platelets / virology*
  • Blood Transfusion
  • Cytotoxicity, Immunologic
  • Hemorrhage / metabolism*
  • Integrin beta3 / metabolism
  • Interferon-alpha / metabolism*
  • Interferon-beta / metabolism*
  • Lymphocytic Choriomeningitis / virology*
  • Lymphocytic choriomeningitis virus / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • T-Lymphocytes, Cytotoxic / metabolism*
  • T-Lymphocytes, Cytotoxic / virology*
  • Thrombocytopenia / virology

Substances

  • Integrin beta3
  • Interferon-alpha
  • Interferon-beta