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Blood, 1 December 2006, Vol. 108, No. 12, pp. 3691-3699.
Prepublished online as a Blood First Edition Paper on August 24, 2006; DOI 10.1182/blood-2005-12-026682.
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Submitted December 30, 2005
Accepted July 24, 2006
Viral gene expression during the establishment of human cytomegalovirus latent infection in myeloid progenitor cells
Allen K.L. Cheung, Allison Abendroth, Anthony L. Cunningham, and Barry Slobedman*
Westmead Millennium Institute and University of Sydney, Westmead, New South Wales, Australia
* Corresponding author; email: barry_slobedman{at}wmi.usyd.edu.au.
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 ~10 copies. Infectious virus was not detected but virus could be reactivated by extended fibroblast co-culture. In contrast to wild-type HCMV, the viral genome was rapidly lost from myeloid progenitors infected with 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.
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