Human cytomegalovirus (HCMV) is an undisputed pathogen in humans with severe immune compromise, which has historically been thought to carry little consequence in immunocompetent hosts. During the past decade, however, accumulating data suggest that significant numbers of immunocompetent humans reactivate HCMV during critical illness, and that these reactivation episodes are associated with worsened outcomes. Because most people are infected with this ubiquitous virus by adulthood, confirming pathogenicity has now become a clinical priority. In this article, we will review the incidence and implications of reactivation, the relevant immune responses and reactivation triggers relevant to the immunocompetent host. We will summarize the progress made during the past ten years, outline the work ongoing in this field, and identify the major gaps remaining in our emerging understanding of this phenomenon.
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