Mature B cells are required for acute splenic infection, but not for establishment of latency, by murine gammaherpesvirus 68.

  • Weck K
  • Barkon M
  • Yoo L
 et al. 
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Abstract

Murine gammaherpesvirus 68 (gamma HV-68; also referred to as MHV-68) is a gammaherpesvirus which infects murid rodents. Previous studies showed that CD8 T cells are important for controlling gamma HV-68 replication during the first 2 weeks of infection and suggested a role for B cells in latent or persistent gamma HV-68 infection. To further define the importance of B cells and CD8 T cells during acute and chronic gamma HV-68 infection, we examined splenic infection in mice with null mutations in the transmembrane domain of the mu-heavy-chain constant region (MuMT; B-cell and antibody deficient) or in the beta2-microglobulin gene (beta2 -/-; CD8 deficient). Immunocompetent mice infected intraperitoneally with gamma HV-68 demonstrated peak splenic titers 9 to 10 days postinfection, cleared infectious virus 15 to 20 days postinfection, and harbored low levels of latent virus at 6 weeks postinfection. Beta2-/- mice showed peak splenic gamma HV-68 titers similar to those of normal mice but were unable to clear infectious virus completely from the spleen, demonstrating persistent infectious virus 6 weeks postinfection. These data indicate that CD8 T cells are important for clearing infectious gamma HV-68 from the spleen. Infected MuMT mice did not demonstrate detectable infectious gamma HV-68 in the spleen at any time after infection, indicating that mature B lymphocytes are necessary for acute splenic infection by gamma HV-68. Despite the lack of measurable acute infection, MuMT spleen cells harbored latent virus 6 weeks postinfection at a level about 100-fold higher than that in normal mice. These data demonstrate establishment of latency by a herpesvirus in an organ in the absence of acute viral replication in that organ. In addition, they demonstrate that gamma HV-68 can establish latency in a cell type other than mature B lymphocytes.

Author-supplied keywords

  • Acute Disease
  • Animals
  • B-Lymphocytes
  • B-Lymphocytes: immunology
  • B-Lymphocytes: pathology
  • Cell Differentiation
  • Gammaherpesvirinae
  • Gammaherpesvirinae: physiology
  • Herpesviridae Infections
  • Herpesviridae Infections: immunology
  • Mice
  • Spleen
  • Spleen: immunology
  • Spleen: pathology
  • Spleen: virology
  • Virus Activation
  • Virus Latency

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Authors

  • K E Weck

  • M L Barkon

  • L I Yoo

  • S H Speck

  • I V Virgin HW

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