Clinical and biologic aspects of human cytomegalovirus resistance to antiviral drugs.
The emergence of human cytomegalovirus (HCMV) drug resistant strains is a life-threatening condition in immunocompromised individuals with active HCMV infection. HCMV drug resistance represented a major problem in patients with acquired immunodeficiency syndrome until the recent introduction of highly active antiretroviral combination therapy, which dramatically decreased the incidence in this clinical setting. However, HCMV resistance to antiviral drugs is now an emerging problem in the transplantation setting. The molecular mechanisms of HCMV drug resistance have been elucidated and rely on the selection during treatment of HCMV strains harboring mutations in two key viral genes: UL97 coding for a viral phosphotransferase and UL54 coding for the viral DNA polymerase.
Baldanti
Fausto
F
Servizio di Virologia, IRCCS Policlinico San Matteo, Pavia, Italy.
Lurain
Nell
N
Gerna
Giuseppe
G
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000188:drug therapy; D023241:Antiretroviral Therapy, Highly Active; D000077404:Cidofovir; D003587:Cytomegalovirus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D003586:Cytomegalovirus Infections / Q000150:complications / Q000188:drug therapy*; D003596:Cytosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism; D024882:Drug Resistance, Viral / Q000235:genetics*; D017245:Foscarnet / Q000627:therapeutic use; D015774:Ganciclovir / Q000627:therapeutic use; D006801:Humans; D009154:Mutation / Q000235:genetics; D063065:Organophosphonates / Q000627:therapeutic use; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
D063065:Organophosphonates; C109367:UL54 protein, Human herpesvirus 5; D014764:Viral Proteins; D017245:Foscarnet; D003596:Cytosine; D017853:Phosphotransferases (Alcohol Group Acceptor); C075365:ganciclovir kinase; D004259:DNA-Directed DNA Polymerase; D000077404:Cidofovir; D015774:Ganciclovir