title: Epstein-Barr virus IL-10 gene expression by a recombinant murine gammaherpesvirus in vivo enhances acute pathogenicity but does not affect latency or reactivation.
abstract: BACKGROUND
  Many viral genes affect cytokine function within infected hosts, with interleukin 10 (IL-10) as a commonly targeted mediator. Epstein-Barr virus (EBV) encodes an IL-10 homologue (vIL-10) expressed during productive (lytic) infection and induces expression of cellular IL-10 (cIL-10) during latency. This study explored the role of vIL-10 in a murine gammaherpesvirus (MHV) model of viral infection.
  
  
  METHODS
  The EBV vIL-10 gene was inserted into MHV-76, a strain which lacks the ability to induce cIL-10, by recombination in transfected mouse cells. Mice were infected intranasally with the recombinant, vIL-10-containing MHV-76 or control virus strains and assayed at various days post infection for lung virus titer, spleen cell number, percentage of latently infected spleen cells and ability to reactivate virus from spleen cells.
  
  
  RESULTS
  Recombinant murine gammaherpesvirus expressing EBV vIL-10 rose to significantly higher titers in lungs and promoted an increase in spleen cell number in infected mice in comparison to MHV strains lacking the vIL-10 gene. However, vIL-10 expression did not alter the quantity of latent virus in the spleen or its ability to reactivate.
  
  
  CONCLUSIONS
  In this mouse model of gammaherpesvirus infection, EBV vIL-10 appears to influence acute-phase pathogenicity. Given that EBV and MHV wild-type strains contain other genes that induce cIL-10 expression in latency (e.g. LMP-1 and M2, respectively), vIL-10 may have evolved to serve the specific role in acute infection of enlarging the permissive host cell population, perhaps to facilitate initial survival and dissemination of viral-infected cells.
authors.affiliation: Department of Biology, Rhodes College, Memphis, TN 38112, USA.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Lindquester
authors.affiliation: Department of Biology, Rhodes College, Memphis, TN 38112, USA.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Greer
authors.affiliation: Department of Infection Biology, Institute of Infection and Global Health, University of Liverpool, Liverpool L3 5RF, UK.
authors.forename: James P
authors.initials: JP
authors.lastname: Stewart
authors.affiliation: Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN 38105, USA ; Current Address: Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Jeffery T
authors.initials: JT
authors.lastname: Sample
keywords: Epstein-Barr virus; Gammaherpesvirus; IL-10; Immune modulation; Interleukin 10