The m4 gene of murine gammaherpesvirus modulates productive and latent infection in vivo

A C Townsley, B M Dutia, A A Nash

Research output: Contribution to journalArticlepeer-review

Abstract

Murine gammaherpesvirus 68 (MHV-68) infection of mice represents a viable small-animal model for the study of gammaherpesvirus pathogenesis. MHV-76 is a deletion mutant of MHV-68, which lacks four MHV-68-specific genes (M1 to M4) and eight viral tRNA-like sequences at the 5' end of the genome. These genes are implicated in latency and/or immune evasion. Consequently, MHV-76 is attenuated in the acute phase of in vivo infection with respect to MHV-68. Little is known about the role of M4 in viral infection, except that it is expressed as an immediate-early/early transcript during lytic replication of MHV-68 in vitro. To elucidate the contribution M4 makes to in vivo pathogenesis, we created a novel MHV-76 mutant (MHV-76inM4), in which the region of MHV-68 coding for M4 and accompanying putative promoter elements were inserted into the 5' region of the MHV-76 genome. The growth of MHV-76inM4 in vitro was indistinguishable from that of MHV-76 and MHV-68. However, virus titers from MHV-76inM4-infected BALB/c mice were significantly increased with respect to MHV-76 at early times in the lung. In addition, at days 17 and 21 postinfection, there was a significant elevation in latent viral load in splenocytes of MHV-76inM4-infected mice compared to MHV-76. Like MHV-76-infected mice, MHV-76inM4-infected mice display no evidence of overt splenomegaly, a finding characteristic of MHV-68 infection. M4 expression in vivo was detectable during productive infection in the lung and during the establishment of latency in the spleen, but in general M4 was not detectable during long-term latency (day 100 postinfection).
Original languageEnglish
Pages (from-to)758-67
Number of pages10
JournalJournal of Virology
Volume78
Issue number2
Publication statusPublished - Jan 2004

Keywords

  • Animals
  • Cell Line
  • Cricetinae
  • Female
  • Gammaherpesvirinae
  • Gene Expression Regulation, Viral
  • Herpesviridae Infections
  • Immediate-Early Proteins
  • Mice
  • Mice, Inbred BALB C
  • Transcription, Genetic
  • Virulence
  • Virus Activation
  • Virus Latency
  • Virus Replication

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