Murine cytomegalovirus encodes a stable intron that facilitates pesistent replication in the mouse

Caroline A. Kulesza, Thomas Shenk

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

The human cytomegalovirus immediate-early 5-kb RNA previously has been shown to be a stable intron that is not required for efficient replication of the virus in cultured fibroblasts. Here we describe a murine cytomegalovirus 7.2-kb ortholog of the human cytomegalovirus 5-kb RNA. The 5′ end of the 7.2-kb transcript maps to a consensus splice-donor site that is conserved among all cytomegaloviruses. We constructed mutant viruses lacking the entire 7.2-kb coding domain, the splice-donor site predicted to function in the generation of the intron or a hairpin predicted to stabilize the intron. All three mutant viruses failed to produce the 7.2-kb RNA, supporting our conclusion that it is a stable intron. Each of the mutants replicated with normal kinetics in cultured fibroblasts, but the mutants exhibited a clear defect within infected mice. Although the initial acute phase at 4 days after infection appeared to be normal, none of the mutant viruses progressed to the persistent phase, i.e., little virus was detected in the salivary gland at 14 days after infection. The intron functions as an in vivo virulence factor, facilitating progression from the acute to persistent phase of infection.

Original languageEnglish (US)
Pages (from-to)18302-18307
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number48
DOIs
StatePublished - Nov 28 2006

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • RNA processing
  • Salivary gland
  • Viral pathogenesis

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