Abstract
BackgroundMany 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.MethodsThe 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.ResultsRecombinant 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.ConclusionsIn 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.
Highlights
Many viral genes affect cytokine function within infected hosts, with interleukin 10 (IL-10) as a commonly targeted mediator
The new constructs were successful in expressing vIL-10 in NIH-3T3 cells with similar expression levels in uninfected cells and in cells infected with murine gammaherpesvirus (MHV)-76 (Figure 2)
The gp150-promoter/vIL-10 cassette was inserted between the terminal repeat and the unique sequences of the left hand end of the cloned MHV-76 DNA to create the targeting cassette (Figure 1)
Summary
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. Viruses from a range of virus families exert direct influence on host cytokine responses Such influence can be mediated through expression of viral homologs of host cytokines or cytokine receptors, or through expression of viral factors that alter expression of host cytokines [1,2,3]. The viral and cellular homologs share many immunosuppressive activities, while vIL-10 generally lacks cIL-10’s immunostimulatory functions. These differences are attributed primarily to a single amino acid substitution [24]
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