Efficient replication of rhesus cytomegalovirus variants in multiple rhesus and human cell types

Anders E. Lilja, Thomas Shenk

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

Rhesus cytomegalovirus infection of rhesus macaques has emerged as a model for human cytomegalovirus pathogenesis. The UL128-UL131 locus of the human virus is a primary determinant for viral entry into epithelial cells, an important cell type during cytomegalovirus infection. Rhesus cytomegalovirus strain 68-1 spreads slowly when grown in cultured rhesus epithelial cells, and it does not code for ORFs corresponding to UL128 and the second exon of UL130. We repaired the UL128-UL131 locus of strain 68-1, using rhesus cytomegalovirus strain 180.92 as template, to generate BRh68-1.1. We also repaired a mutation in the UL36 ORF in BRh68-1.1 to make BRh68-1.2. Both repaired derivatives replicate much more efficiently than parental 68-1 virus in rhesus epithelial cells, suggesting that strain 68-1 may be attenuated. Intriguingly, BRh68-1.1 and BRh68-1.2 replicate efficiently in cultured human epithelial cells and endothelial cells. The extended human cell host range of the repaired viruses raises the possibility that rhesus cytomegalovirus-like viruses will be found in humans.

Original languageEnglish (US)
Pages (from-to)19950-19955
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number50
DOIs
StatePublished - Dec 16 2008

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Cross-species infection
  • Cytomegalovirus pathogenesis
  • Epithelial cells

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