Role of molecular mimicry of hepatitis C virus protein with platelet GPIIIa in hepatitis C-related immunologic thrombocytopenia

Blood. 2009 Apr 23;113(17):4086-93. doi: 10.1182/blood-2008-09-181073. Epub 2008 Nov 20.


Patients with HIV-1 immune-related thrombocytopenia (HIV-1-ITP) have a unique Ab against platelet GPIIIa49-66 capable of inducing oxidative platelet fragmentation in the absence of complement. HIV-1-seropositive drug abusers are more prone to develop immune thrombocytopenia than non-drug abusers and have a higher coinfection with hepatitis C virus (HCV) than non-drug abusers (90% vs 30%). Molecular mimicry was sought by screening a phage peptide library with anti-GPIIIa49-66 antibody as bait for peptides sharing homology sequences with HCV. Several phage peptide clones had 70% homology with HCV protein. Sera from dually infected thrombocytopenic patients with HCV and HIV-ITP reacted strongly with 4 nonconserved peptides from HCV core envelope 1. Reactivity correlated inversely with platelet count (r(2) = 0.7, P < .01). Ab raised against peptide PHC09 in GPIIIa(-/-) mice induced thrombocytopenia in wild-type mice. Affinity-purified IgG against PHC09 induced oxidative platelet fragmentation in vitro. Drug abusers dually infected with HCV and HIV-1 had a greater incidence and severity of thrombocytopenia as well as titer of anti-GPIIIa49-66/PHC09 Ab. NZB/W F1 mice injected with recombinant core envelope 1 developed Ab versus PHC09 and significantly decreased their platelet count (P < .001). Thus, HCV core envelope 1 can induce thrombocytopenia by molecular mimicry with GPIIIa49-66.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / immunology
  • Blood Platelets / metabolism
  • Cell Count
  • Cross Reactions / immunology
  • Female
  • Hepacivirus
  • Hepatitis C / complications
  • Hepatitis C / genetics
  • Hepatitis C / immunology*
  • Hepatitis C / metabolism*
  • Integrin beta3 / genetics
  • Integrin beta3 / metabolism*
  • Mice
  • Mice, Knockout
  • Molecular Mimicry*
  • Oxidative Stress
  • Peptide Library
  • Thrombocytopenia / etiology
  • Thrombocytopenia / genetics
  • Thrombocytopenia / immunology*
  • Thrombocytopenia / metabolism*
  • Viral Envelope Proteins / immunology
  • Viral Envelope Proteins / metabolism*


  • Antibodies, Viral
  • Integrin beta3
  • Peptide Library
  • Viral Envelope Proteins