PMID- 18241936
OWN - NLM
STAT- MEDLINE
DCOM- 20080422
LR  - 20181201
IS  - 0166-3542 (Print)
IS  - 0166-3542 (Linking)
VI  - 77
IP  - 3
DP  - 2008 Mar
TI  - Characterization of a cidofovir-resistant HHV-6 mutant obtained by in vitro 
      selection.
PG  - 237-40
LID - 10.1016/j.antiviral.2007.12.004 [doi]
AB  - Cidofovir (CDV) was used for in vitro selection of a human herpesvirus 6 (HHV-6) 
      mutant with decreased susceptibility to this drug. The resulting mutant was 
      highly resistant to CDV as compared to its sensitive counterpart (inhibitory 
      concentration 50% (IC50): 213 microM versus 1.8 microM). Its replication fitness 
      was not impaired. Genotypic characterization of the resistant virus revealed a 
      mutation in the U38 gene encoding the viral DNA polymerase. The resulting R798I 
      amino acid change was located in the conserved domain VII close to the highly 
      conserved motif KKRY interacting with the DNA primer-template duplex, and is 
      likely responsible for the high-level resistance to CDV, even though a definite 
      virological and/or biochemical confirmation is required. The possible emergence 
      of such changes in HHV-6 DNA polymerase in patients receiving CDV therapy should 
      be taken into account in the treatment of HHV-6 infections.
FAU - Bonnafous, Pascale
AU  - Bonnafous P
AD  - Universite Pierre et Marie Curie-Paris 6, EA2387, Groupe Hospitalier 
      Pitie-Salpetriere, 83 boulevard de l'Hopital, F-75013 Paris, France. 
      pascale.bonnafous@psl.aphp.fr
FAU - Boutolleau, David
AU  - Boutolleau D
FAU - Naesens, Lieve
AU  - Naesens L
FAU - Deback, Claire
AU  - Deback C
FAU - Gautheret-Dejean, Agnes
AU  - Gautheret-Dejean A
FAU - Agut, Henri
AU  - Agut H
LA  - eng
PT  - Journal Article
DEP - 20080107
PL  - Netherlands
TA  - Antiviral Res
JT  - Antiviral research
JID - 8109699
RN  - 0 (Antiviral Agents)
RN  - 0 (Organophosphonates)
RN  - 0 (Viral Proteins)
RN  - 8J337D1HZY (Cytosine)
RN  - EC 2.7.7.7 (DNA-Directed DNA Polymerase)
RN  - JIL713Q00N (Cidofovir)
SB  - IM
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Antiviral Agents/*pharmacology
MH  - Cidofovir
MH  - Cytosine/*analogs & derivatives/pharmacology
MH  - DNA Mutational Analysis
MH  - DNA-Directed DNA Polymerase/genetics
MH  - *Drug Resistance, Viral
MH  - Herpesvirus 6, Human/*drug effects/*genetics/growth & development/physiology
MH  - Inhibitory Concentration 50
MH  - Molecular Sequence Data
MH  - Mutation, Missense
MH  - Organophosphonates/*pharmacology
MH  - Viral Proteins/genetics
MH  - Virus Replication
EDAT- 2008/02/05 09:00
MHDA- 2008/04/23 09:00
CRDT- 2008/02/05 09:00
PHST- 2007/10/01 00:00 [received]
PHST- 2007/11/12 00:00 [revised]
PHST- 2007/12/10 00:00 [accepted]
PHST- 2008/02/05 09:00 [pubmed]
PHST- 2008/04/23 09:00 [medline]
PHST- 2008/02/05 09:00 [entrez]
AID - S0166-3542(07)00500-1 [pii]
AID - 10.1016/j.antiviral.2007.12.004 [doi]
PST - ppublish
SO  - Antiviral Res. 2008 Mar;77(3):237-40. doi: 10.1016/j.antiviral.2007.12.004. Epub 
      2008 Jan 7.