The myeloid transcription factor GATA-2 regulates the viral UL144 gene during human cytomegalovirus latency in an isolate-specific manner.
It is generally accepted that, following primary infection, human cytomegalovirus (HCMV) establishes lifelong latency in CD34(+) progenitor cells and other derivative cells of the myeloid lineage. In this study, we show that the viral UL144 gene is expressed during latent infection in two cell types of the myeloid lineage, CD34(+) and CD14(+) monocytes, and that the UL144 protein is functional in latently infected monocytes. However, this latency-associated expression of UL144 occurs only in certain isolates of HCMV and depends on the presence of functional GATA-2 transcription factor binding sites in the UL144 promoter, in contrast to the viral latency-associated gene LUNA, which we also show is regulated by GATA-2 but expressed uniformly during latent infection independent of the virus isolate. Taken together, these data suggest that the HCMV latency-associated transcriptome may be virus isolate specific and dependent on the repertoire of transcription factor binding sites in the promoters of latency-associated genes.
University of Cambridge, Department of Medicine, Cambridge, United Kingdom.
Emma
E
Poole
Anett
A
Walther
Kathy
K
Raven
Christopher A
CA
Benedict
Gavin M
GM
Mason
John
J
Sinclair
D018952:Antigens, CD34 / Q000032:analysis; D003587:Cytomegalovirus / Q000502:physiology*; D050989:GATA2 Transcription Factor; D054884:Host-Pathogen Interactions; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009000:Monocytes / Q000737:chemistry / Q000821:virology; D014764:Viral Proteins / Q000378:metabolism*; D017735:Virus Latency
D018952:Antigens, CD34; D050989:GATA2 Transcription Factor; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; C119624:UL144 ORF protein, Human herpesvirus 5; D014764:Viral Proteins