Important role for the murid herpesvirus 4 ribonucleotide reductase large subunit in host colonization via the respiratory tract

J Virol. 2010 Oct;84(20):10937-42. doi: 10.1128/JVI.00828-10. Epub 2010 Jul 28.

Abstract

Viral enzymes that process small molecules provide potential chemotherapeutic targets. A key constraint-the replicative potential of spontaneous enzyme mutants-has been hard to define with human gammaherpesviruses because of their narrow species tropisms. Here, we disrupted the murid herpesvirus 4 (MuHV-4) ORF61, which encodes its ribonucleotide reductase (RNR) large subunit. Mutant viruses showed delayed in vitro lytic replication, failed to establish infection via the upper respiratory tract, and replicated to only a very limited extent in the lower respiratory tract without reaching lymphoid tissue. RNR could therefore provide a good target for gammaherpesvirus chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • Cricetinae
  • DNA, Viral / genetics
  • Genes, Viral
  • Herpesviridae Infections / virology
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mutagenesis, Insertional
  • Respiratory System / virology
  • Rhadinovirus / enzymology*
  • Rhadinovirus / genetics
  • Rhadinovirus / pathogenicity*
  • Ribonucleotide Reductases / chemistry
  • Ribonucleotide Reductases / genetics
  • Ribonucleotide Reductases / physiology*
  • Tumor Virus Infections / virology
  • Virulence / genetics
  • Virulence / physiology
  • Virus Replication / genetics
  • Virus Replication / physiology

Substances

  • DNA, Viral
  • Ribonucleotide Reductases