Cytomegalovirus: genetics of drug resistance.

Abstract

Human cytomegalovirus (CMV) shares the characteristic ability of other herpesviruses to establish persistence or life-long latency following primary infection, and to reactivate subsequently as host cell-mediated immunity diminishes.1 However, CMV has clearly evolved unique strategies for intracellular replication, pathogenesis and persistence in the host. The regulatory mechanisms and biological sites for viral persistence and reactivation of CMV are poorly understood, but clearly they do not involve the neurotropic pathways employed by herpes simplex virus (HSV) or varicella zoster virus (VZV). CMV infections in immunocompromised patients, especially bone marrow and organ transplant recipients and patients with AIDS, are a major cause of morbidity and mortality. These infections most commonly are reactivations of prior latent infection. Reactivation likely begins with a viremic phase, during which virus can be detected in blood mononuclear cells, followed by symptoms and signs of organ involvement, such as retinitis, pneumonitis, or colitis. Individuals may be infected with multiple strains of CMV, which can reactivate sequentially or simultaneously.2, 3 Different strains or populations of virus may be present at different body sites, with variable accessibility to individual antiviral drugs. Currently approved therapies for the suppression and treatment of CMV include ganciclovir (GCV), foscarnet (PFA), and acyclovir (ACV). Acyclovir is less active in treatment of established CMV infections, but it can reduce the reactivation of latent infection, and resulting CMV disease, in bone marrow and solid organ transplant patients. Several factors point to the likelihood of drug-resistant strains of CMV developing Most disease occurs in immunocompromised patients, who have a high viral load and for whom control of the infection depends almost solely on antiviral therapy. In addition, chronic therapy is frequently necessaryKeywordsHuman CytomegalovirusUL97 GeneSolid Organ Transplant PatientPhosphonoacetic AcidUL97 MutationThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.