Human cytomegalovirus sequences expressed in latently infected individuals promote a latent infection in vitro

Felicia Goodrum, Matthew Reeves, John Sinclair, Kevin High, Thomas Shenk

Research output: Contribution to journalArticlepeer-review

170 Scopus citations

Abstract

Latency enables human cytomegalovirus (HCMV) to persist in the hematopoietic cells of infected individuals indefinitely and prevents clearance of the pathogen. Despite its critical importance to the viral infectious cycle, viral mechanisms that contribute to latency have not been identified. We compared the ability of lowpassage clinical and laboratory-adapted strains of HCMV to establish a latent infection in primary human CD34+ cells. The low-passage strains, Toledo and FIX, established an infection with the hallmarks of latency, whereas the laboratory strains, AD169 and Towne, replicated producing progeny virus. We hypothesized that ULb′ region of the genome, which is unique to low-passage strains, may encode a latency-promoting activity. We created and analyzed recombinant viruses lacking segments or individual open reading frames (ORFs) in the ULb′ region. One 5-kb segment, and more specifically the UL138 ORF, was required for HCMV to establish and/or maintain a latent infection in hematopoietic progenitor cells infected in vitro. This is the first functional demonstration of a virus-coded sequence required for HCMV latency. Importantly, UL138 RNAwas expressed in CD34+ cells and monocytes from HCMV-seropositive, healthy individuals. UL138 might be a target for antivirals against latent virus.

Original languageEnglish (US)
Pages (from-to)937-945
Number of pages9
JournalBlood
Volume110
Issue number3
DOIs
StatePublished - Aug 1 2007

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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