J Bacteriol Virol.  2015 Mar;45(1):11-18. 10.4167/jbv.2015.45.1.11.

Human Cytomegalovirus Infection in Solid-Organ Transplantation

• Kim YH

• KMID: 2168699
• DOI: http://doi.org/10.4167/jbv.2015.45.1.11

Abstract

Human cytomegalovirus (CMV) continues to be a major threat against solid-organ transplant recipients despite significant advancements in its prophylaxis and therapy. Primary CMV infection or reactivation of latent CMV in the transplant recipients may cause CMV diseases such as flu-like viral syndrome and tissue-invasive CMV disease. In addition, CMV infection in the recipients is associated with graft rejection and higher risk of other opportunistic infections, which are collectively known as the "indirect effects" of CMV infection. Prevention strategies with antiviral drugs including ganciclovir remarkably decreased CMV disease and the "indirect effects". Two commonly employed strategies are universal prophylaxis and preemptive therapy. However, gangciclovir-resistant CMV has emerged due to mutations in CMV UL97 and UL54 genes, now requiring alternative therapeutic options to be developed. This review provides an overview of CMV infection and disease, "indirect effects" on hosts, prevention strategies, and drug resistance in solid-organ transplant recipients.

Keyword

Cytomegalovirus; Organ transplantation; Immunocompromised hosts

MeSH Terms

Antiviral Agents
Cytomegalovirus
Cytomegalovirus Infections*
Drug Resistance
Ganciclovir
Graft Rejection
Humans
Immunocompromised Host
Opportunistic Infections
Organ Transplantation
Transplantation
Antiviral Agents
Ganciclovir

Figure

• 

  Figure 1. Ganciclovir metabolism and mode of action. Ganciclovir requires three consecutive phosphorylation steps for its antiviral activity. The first phosphorylation step is carried out by a viral phosphotransferase encoded by CMV UL97 gene. Cellular kinases catalyze two additional rounds of phosphorylation. Ganciclovir triphosphate is a competitive inhibitor of dGTP (deoxyguanosine triphosphate), and preferentially inhibits viral DNA polymerases encoded by CMV UL54 gene. Valganciclovir is a prodrug of ganciclovir.

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