Experimental rhesus lymphocryptovirus infection in immunosuppressed macaques: an animal model for Epstein-Barr virus pathogenesis in the immunosuppressed host

Blood. 2004 Sep 1;104(5):1482-9. doi: 10.1182/blood-2004-01-0342. Epub 2004 May 18.

Abstract

To develop a model for Epstein-Barr virus (EBV) pathogenesis in immunosuppressed hosts, we studied experimental infections of immunocompetent versus SHIV 89.6P-infected, immunosuppressed rhesus macaques with the EBV-related rhesus lymphocryptovirus (LCV). Primary LCV infection after oral inoculation of 4 immunocompetent animals was characterized by an acute viremia and seroconversion followed by asymptomatic LCV persistence. Four immunosuppressed macaques infected orally with LCV failed to develop an LCV-specific humoral response and viremia was more pronounced, but there was no evidence of LCV-induced lymphoproliferative disease. A more aggressive primary challenge was administered by intravenous inoculation of 10(8) autologous, LCV-immortalized B cells in 4 additional immunosuppressed animals. Two animals with modest immunosuppression remained asymptomatic, and 1 of 2 severely immunosuppressed animals developed an aggressive, monoclonal LCV-positive lymphoma. These studies demonstrate the potential for lymphomagenesis in an experimental model system for EBV infection and underscore the strength and depth of immune control in limiting LCV-induced lymphoproliferative disease.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Viral / blood
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / virology
  • CD4 Lymphocyte Count
  • Cell Line, Transformed
  • Disease Models, Animal*
  • Epstein-Barr Virus Infections / complications
  • Epstein-Barr Virus Infections / immunology*
  • Herpesviridae Infections / complications
  • Herpesviridae Infections / immunology*
  • Immunocompetence
  • Immunocompromised Host
  • Lymphocryptovirus*
  • Lymphoma / immunology
  • Lymphoma / virology
  • Macaca mulatta*
  • Simian Acquired Immunodeficiency Syndrome / immunology
  • Viral Load
  • Viremia / immunology

Substances

  • Antibodies, Viral