New Insights into the Molecular Mechanisms and Immune Control of Cytomegalovirus Reactivation

Taylor A. Heald-Sargent, Eleonora Forte, Xuefeng Liu, Edward B. Thorp, Michael Messod Abecassis, Zheng Jenny Zhang*, Mary A. Hummel

*Corresponding author for this work

Research output: Contribution to journalReview article

Abstract

Cytomegalovirus (CMV) is a β-herpesvirus that establishes lifelong latency in infected hosts. Following transplantation of a latently infected organ, reactivation can occur and consists of a spectrum of clinically apparent syndromes from mild symptoms to tissue-invasive, resulting in both direct and indirect sequelae. Before the advent of effective antiviral agents, the primary treatment was reduction in immunosuppression (IS). While antiviral agents provide effective prophylaxis, there are several important caveats associated with their use, including drug toxicity and resistance. The traditional view attributes CMV reactivation and the ensuing clinical disease primarily to IS, either intrinsic to disease-related immune compromise or from the extrinsic administration of IS agents. However, previous data from both animal models and human subjects showed that inflammatory signals could induce upregulation of latent viral gene expression. New data demonstrate that ischemia/reperfusion is necessary and sufficient to induce CMV reactivation following murine transplantation of a latently infected graft. In this article, we review a growing body of evidence that suggests that reactivation of both human CMV and murine CMV is first triggered by molecular events that activate CMV gene expression and lytic infection and viral dissemination are then facilitated by IS. The initial activation of viral gene expression may be mediated by oxidative stress, DNA damage, or inflammatory cytokines, and these factors may act synergistically. New therapeutic approaches are needed to capture this complex array of targets.

Original languageEnglish (US)
Pages (from-to)E118-E124
JournalTransplantation
DOIs
StateAccepted/In press - Jan 1 2020

ASJC Scopus subject areas

  • Transplantation

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