Impact of human cytomegalovirus latent infection on myeloid progenitor cell gene expression.
Herpesviruses establish lifelong latent infections in their hosts. Human cytomegalovirus (CMV) targets a population of bone marrow-derived myeloid lineage progenitor cells that serve as a reservoir for reactivation; however, the mechanisms by which latent CMV infection is maintained are unknown. To gain insights into mechanisms of maintenance and reactivation, we employed microarrays of approximately 26,900 sequence-verified human cDNAs to assess global changes in cellular gene expression during experimental CMV latent infection of granulocyte-macrophage progenitors (GM-Ps). This analysis revealed at least 29 host cell genes whose expression was increased and six whose expression was decreased during CMV latency. These changes in transcript levels appeared to be authentic, judging on the basis of further analysis of a subset by semiquantitative reverse transcription-PCR. This study provides a comprehensive snapshot of changes in host cell gene expression that result from latent infection and suggest that CMV regulates genes that encode proteins involved in immunity and host defense, cell growth, signaling, and transcriptional regulation. The host genes whose expression we found altered are likely to contribute to an environment that sustains latent infection.
Slobedman
Barry
B
Centre for Virus Research, Westmead Millennium Institute and University of Sydney, Westmead, New South Wales 2145, Australia. barry_slobedman@wmi.usyd.edu.au
Stern
J Lewis
JL
Cunningham
Anthony L
AL
Abendroth
Allison
A
Abate
Davide A
DA
Mocarski
Edward S
ES
D001483:Base Sequence; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000472:pathogenicity*; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000821:virology; D018076:DNA, Complementary / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D023461:Myeloid Progenitor Cells / Q000502:physiology* / Q000821:virology*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018076:DNA, Complementary