2020/01/30 by Taylor Heald‐Sargent, Taylor A. Heald-Sargent, Eleonora Forte +7 · 28 citations
Immunology and Microbiology · Medicine · #Betaherpesvirinae #Biology #Cytomegalovirus #Cytomegalovirus and herpesvirus research #Disease #Downregulation and upregulation #Gene #Genetics #Herpesviridae #Herpesvirus Infections and Treatments #Human cytomegalovirus #Immune system #Immunology #Immunosuppression #Lytic cycle #Medicine #Pathology #Toxoplasma gondii Research Studies #Transplantation #Viral disease #Viral replication #Virology #Virus #Virus latency
paper · open access · doi:10.1097/tp.0000000000003138
published in Transplantation 104(5), e118-e124 (Wolters Kluwer)
openalex publication_date 2020/01/30 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
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.