The pathogenesis and clinical management of cytomegalovirus infection in the organ transplant recipient: the end of the 'silo hypothesis'.
OBJECTIVE
Cytomegalovirus infection is initiated when tumor necrosis factor binds to the cytomegalovirus receptors of latently infected cells, resulting in the reactivation of the virus and the production of clinical disease of two types: direct infection causing pneumonia, mononucleosis, colitis and other viral-related syndromes, and indirect infection in which an array of cytokines are released by the host that produce much the same effect as does the rejection process.


RESULTS
These effects fall into three categories: allograft injury, an increase in superinfection with opportunistic pathogens and an increase in the incidence of B cell lymphoproliferative disease. Other factors that modulate the clinical impact of reactivated cytomegalovirus in the transplant patient include the past experience of the host with the virus (primary infection, donor seropositive and recipient seronegative), the degree of major histocompatibility complex mismatch, the viral burden and the amount of calcineurin inhibitor the patient receives.


CONCLUSIONS
Optimal therapy for diagnosing, treating and preventing these indirect effects still remains to be defined; the direct effects, in contrast, are well managed with valganciclovir.
Rubin
Robert H
RH
Harvard Medical School, Center for Experimental Pharmacology and Therapeutics, Harvard-MIT Division of Health Sciences and Technology, Division of Infectious Disease, Brigham and Women's Hospital, Boston, Massachusetts, USA. rhrubin@partners.org
D000998:Antiviral Agents / Q000627:therapeutic use*; D003587:Cytomegalovirus / Q000276:immunology / Q000472:pathogenicity*; D003586:Cytomegalovirus Infections / Q000150:complications / Q000188:drug therapy* / Q000517:prevention & control / Q000821:virology*; D006084:Graft Rejection / Q000821:virology; D006801:Humans; D016867:Immunocompromised Host; D008232:Lymphoproliferative Disorders / Q000209:etiology; D011183:Postoperative Complications / Q000188:drug therapy / Q000517:prevention & control / Q000821:virology; D014180:Transplantation
D000998:Antiviral Agents