Viral gene expression during the establishment of human cytomegalovirus latent infection in myeloid progenitor cells.
Human cytomegalovirus (HCMV) establishes and maintains a latent infection in myeloid cells and can reactivate to cause serious disease in allograft recipients. To better understand the molecular events associated with the establishment of latency, we tracked the virus following infection of primary human myeloid progenitor cells at days 1, 2, 3, 5, and 11. At all time points, the viral genome was maintained in most cells at approximately 10 copies. Infectious virus was not detected, but virus could be reactivated by extended fibroblast coculture. In contrast to wild-type HCMV, the viral genome was rapidly lost from myeloid progenitors infected with ultraviolet (UV)-inactivated virus, suggesting viral gene expression was required for efficient establishment of latency. To identify viral genes associated with the establishment phase, RNA from each time point was interrogated using custom-made HCMV gene microarrays. Using this approach, we detected expression of viral RNAs at all time points. The pattern of expression differed from that which occurs during productive infection, and decreased over time. This study provides evidence that a molecular pathway into latency is associated with expression of a unique subset of viral transcripts. Viral genes expressed during the establishment phase may serve as targets for therapies to interrupt this process.
Cheung
Allen K L
AK
Centre for Virus Research, Westmead Millennium Institute, PO Box 412, Westmead, NSW 2145, Australia.
Abendroth
Allison
A
Cunningham
Anthony L
AL
Slobedman
Barry
B
D002478:Cells, Cultured; D018920:Coculture Techniques; D003587:Cytomegalovirus / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control; D005347:Fibroblasts / Q000378:metabolism / Q000821:virology; D020869:Gene Expression Profiling / Q000379:methods; D015967:Gene Expression Regulation, Viral / Q000502:physiology* / Q000528:radiation effects; D016679:Genome, Viral / Q000502:physiology / Q000528:radiation effects; D006801:Humans; D023461:Myeloid Progenitor Cells / Q000378:metabolism / Q000821:virology*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012367:RNA, Viral / Q000378:metabolism; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D014466:Ultraviolet Rays; D014467:Ultraviolet Therapy / Q000379:methods; D014775:Virus Activation / Q000502:physiology* / Q000528:radiation effects; D038301:Virus Inactivation / Q000528:radiation effects; D017735:Virus Latency / Q000502:physiology* / Q000528:radiation effects
D012367:RNA, Viral