Cytomegalovirus reactivation in critically ill immunocompetent hosts: A decade of progress and remaining challenges

Abstract

Human cytomegalovirus (HCMV) is an undisputed pathogen in humans with severe immunocompromise that has historically been thought to carry little consequence in immunecompetent 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 work ongoing in this field, and identify the major gaps remaining in our emerging understanding of this phenomenon.

Activation of Human Herpesvirus Replication by Apoptosis

“…In addition to the fact that these viruses represent a cross-section of human herpes-virus families, we also chose these herpesviruses because good latently infected cell line model systems exist for them and because they cause close to universal infections in humans by an early age (14)(15)(16)(17), making the clinical and translational implications of the studies more compelling. These viruses have been associated with significant adverse clinical outcomes in clinical situations in which substantial numbers of cells may be undergoing apoptosis, such as treatment with cytotoxic cancer chemotherapeutic agents, solid organ and bone marrow transplantation (18,19), and severe hypersensitivity and autoimmune disorders (20)(21)(22)(23)(24), and in patients critically ill from a variety of causes (25). Human herpesviruses have been implicated in a variety of incompletely understood clinical disorders (26), some of which may be associated with apoptosis.…”

CMV and transfusions, an old story that's not quite over yet

“…Reactivation" is the "recovery of infectious virus following some period of viral latency." 34 There is evidence for CMV latency in both mice and humans. 34,35 CMV may go latent directly without productive infection or expressing any genes connected with it.…”

“…34 There is evidence for CMV latency in both mice and humans. 34,35 CMV may go latent directly without productive infection or expressing any genes connected with it. Alternatively, a phase of productive infection may be followed by latency.…”

The immunological underpinnings of vaccinations to prevent cytomegalovirus disease

“…22,37 CMV rarely causes disease in the immunocompetent host even in situations such as trauma, which leads to systemic reactivation. 38 Defects in T-cell host defense mechanisms are associated with life-threatening CMV disease, making CMV one of the most significant opportunistic diseases in immunocompromised individuals. Immunosuppression promotes the reactivation of latent viruses, persistent shedding and endorgan disease.…”