Human cytomegalovirus gene expression during infection of primary hematopoietic progenitor cells: A model for latency

Felicia Goodrum, Craig T. Jordan, Kevin High, Thomas Shenk

Research output: Contribution to journalArticle

175 Citations (Scopus)

Abstract

Human cytomegalovirus (HCMV) resides latently in hematopoietic cells of the bone marrow. Although viral genomes can be found in CD14+ monocytes and CD34+ progenitor cells, the primary reservoir for latent cytomegalovirus is unknown. We analyzed human hematopoietic subpopulations infected in vitro with a recombinant virus that expresses a green fluorescent protein marker gene. Although many hematopoietic cell subsets were infected in vitro, CD14+ monocytes and various CD34+ subpopulations were infected with the greatest efficiency. We have developed an in vitro system in which to study HCMV infection and latency in CD34+ cells cultured with irradiated stromal cells. Marker gene expression was substantially reduced by 4 days postinfection, and infectious virus was not made during the culture period. However, viral DNA sequences were maintained in infected CD34+ cells for >20 days in culture, and, importantly, virus replication could be reactivated by coculture with human fibroblasts. Using an HCMV gene array, we examined HCMV gene expression in CD34+ cells. The pattern of viral gene expression was distinct from that observed during productive or nonproductive infections. Some of these expressed viral genes may function in latency and are targets for further analysis. Altered gene expression in hematopoietic progenitors may be indicative of the nature and outcome of HCMV infection.

Original languageEnglish (US)
Pages (from-to)16255-16260
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number25
DOIs
StatePublished - Dec 10 2002
Externally publishedYes

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Hematopoietic Stem Cells
Cytomegalovirus
Gene Expression
Infection
Viral Genes
Cytomegalovirus Infections
Monocytes
Viruses
Viral Genome
Viral DNA
Stromal Cells
Virus Replication
Coculture Techniques
Green Fluorescent Proteins
Bone Marrow Cells
Genes
Cultured Cells
Stem Cells
Fibroblasts
In Vitro Techniques

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Human cytomegalovirus gene expression during infection of primary hematopoietic progenitor cells : A model for latency. / Goodrum, Felicia; Jordan, Craig T.; High, Kevin; Shenk, Thomas.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 25, 10.12.2002, p. 16255-16260.

Research output: Contribution to journalArticle

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