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SUMMARY:Viral DNA polymerase inhibitors: drug resistance among herpesvirus
 es and poxviruses - Professor Graciela Andrei\, Rega Institute for Medical
  Research\, Belgium
DTSTART:20110209T163000Z
DTEND:20110209T173000Z
UID:TALK28477@talks.cam.ac.uk
CONTACT:Suzy Blows
DESCRIPTION:Current drugs licensed for the treatment of herpes simplex vir
 us (HSV) and varicella-zoster virus (VZV) infections include acyclovir (AC
 V)\, penciclovir (PCV)\, brivudin (BVDU) and foscarnet (FOS). Drugs approv
 ed for the treatment of cytomegalovirus (CMV) infections include ganciclov
 ir (GCV)\, foscarnet (FOS)\, cidofovir (CDV) and fomivirsen. Except for fo
 rmivirsen\, all these drugs target the viral DNA polymerase. The nucleosid
 e analogues ACV\, PCV\, GCV and BVDU require activation by viral kinases\,
  i.e. thymidine kinase (TK) (HSV and VZV) and UL97 protein (CMV). Therefor
 e\, resistance to these nucleoside analogues may arise by mutations in the
  enzymes responsible for the activation of these drugs or in the viral DNA
  polymerase. Resistance at the level of the viral DNA polymerase is observ
 ed with PFA\, a direct inhibitor of viral DNA polymerases\, or with acycli
 c nucleoside phosphonates (ANPs) that are independent of viral kinases for
  activation. Although emergence of resistance in herpesviruses is not a pr
 oblem in the immunocompetent population\, it is a concern among the immuno
 compromised population.\nThe following points will be discussed in the sem
 inar:\n• The characterization of HSV\, VZV and CMV mutants arising under
  selective pressure with different classes of ANPs\, as well as with ACV\,
  PCV\, GCV and BVDU. \n• How specific mutations affect viral pathogenici
 ty.\n• Translational research: examples of drug-resistant mutants isolat
 ed from immunocompromised patients. \n• Overview of the mechanisms of an
 tiviral drug resistance among poxviruses\, including the identification of
  residues in the viral DNA polymerase conferring differential resistance t
 o antipoxvirus drugs. \n
LOCATION:Lecture Theatre 1\, Department of Veterinary Medicine
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