PMID- 27694307
OWN - NLM
STAT- MEDLINE
DCOM- 20170606
LR  - 20201209
IS  - 1362-4962 (Electronic)
IS  - 0305-1048 (Print)
IS  - 0305-1048 (Linking)
VI  - 44
IP  - 20
DP  - 2016 Nov 16
TI  - Distribution and effects of amino acid changes in drug-resistant alpha and beta 
      herpesviruses DNA polymerase.
PG  - 9530-9554
AB  - Emergence of drug-resistance to all FDA-approved antiherpesvirus agents is an 
      increasing concern in immunocompromised patients. Herpesvirus DNA polymerase 
      (DNApol) is currently the target of nucleos(t)ide analogue-based therapy. 
      Mutations in DNApol that confer resistance arose in immunocompromised patients 
      infected with herpes simplex virus 1 (HSV-1) and human cytomegalovirus (HCMV), 
      and to lesser extent in herpes simplex virus 2 (HSV-2), varicella zoster virus 
      (VZV) and human herpesvirus 6 (HHV-6). In this review, we present distinct 
      drug-resistant mutational profiles of herpesvirus DNApol. The impact of specific 
      DNApol amino acid changes on drug-resistance is discussed. The pattern of genetic 
      variability related to drug-resistance differs among the herpesviruses. Two 
      mutational profiles appeared: one favoring amino acid changes in the Palm and 
      Finger domains of DNApol (in alpha-herpesviruses HSV-1, HSV-2 and VZV), and another 
      with mutations preferentially in the 3'-5' exonuclease domain (in beta-herpesvirus 
      HCMV and HHV-6). The mutational profile was also related to the class of compound 
      to which drug-resistance emerged.
CI  - (c) The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic 
      Acids Research.
FAU - Topalis, D
AU  - Topalis D
AD  - Rega Institute for Medical Research, Department Microbiology and Immunology, KU 
      Leuven, Minderbroedersstraat 10, 3000, Leuven, Belgium 
      dimitrios.topalis@rega.kuleuven.be.
FAU - Gillemot, S
AU  - Gillemot S
AD  - Rega Institute for Medical Research, Department Microbiology and Immunology, KU 
      Leuven, Minderbroedersstraat 10, 3000, Leuven, Belgium.
FAU - Snoeck, R
AU  - Snoeck R
AD  - Rega Institute for Medical Research, Department Microbiology and Immunology, KU 
      Leuven, Minderbroedersstraat 10, 3000, Leuven, Belgium.
FAU - Andrei, G
AU  - Andrei G
AD  - Rega Institute for Medical Research, Department Microbiology and Immunology, KU 
      Leuven, Minderbroedersstraat 10, 3000, Leuven, Belgium 
      graciela.andrei@rega.kuleuven.be.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20160929
PL  - England
TA  - Nucleic Acids Res
JT  - Nucleic acids research
JID - 0411011
RN  - 0 (Antiviral Agents)
RN  - 0 (Viral Proteins)
RN  - EC 2.7.7.7 (DNA Polymerase I)
RN  - EC 2.7.7.7 (DNA Polymerase beta)
RN  - EC 2.7.7.7 (DNA-Directed DNA Polymerase)
RN  - EC 3.1.- (Exodeoxyribonucleases)
RN  - EC 3.1.11.- (DNA polymerase, Simplexvirus)
SB  - IM
MH  - *Amino Acid Substitution
MH  - Animals
MH  - Antiviral Agents/chemistry/pharmacology
MH  - Catalysis
MH  - Conserved Sequence
MH  - DNA Polymerase I/chemistry/*genetics/*metabolism
MH  - DNA Polymerase beta/chemistry/*genetics/*metabolism
MH  - DNA-Directed DNA Polymerase/chemistry/*genetics/*metabolism
MH  - *Drug Resistance, Viral
MH  - Enzyme Activation
MH  - Evolution, Molecular
MH  - Exodeoxyribonucleases/chemistry/*genetics/*metabolism
MH  - Herpesviridae/classification/drug effects/genetics
MH  - Humans
MH  - Mutation
MH  - Phenotype
MH  - Protein Interaction Domains and Motifs
MH  - Protein Multimerization
MH  - Structure-Activity Relationship
MH  - Viral Proteins/chemistry/*genetics/*metabolism
PMC - PMC5175367
EDAT- 2016/10/04 06:00
MHDA- 2017/06/07 06:00
PMCR- 2016/09/29
CRDT- 2016/10/04 06:00
PHST- 2016/09/21 00:00 [accepted]
PHST- 2016/09/13 00:00 [revised]
PHST- 2016/05/04 00:00 [received]
PHST- 2016/10/04 06:00 [pubmed]
PHST- 2017/06/07 06:00 [medline]
PHST- 2016/10/04 06:00 [entrez]
PHST- 2016/09/29 00:00 [pmc-release]
AID - gkw875 [pii]
AID - 10.1093/nar/gkw875 [doi]
PST - ppublish
SO  - Nucleic Acids Res. 2016 Nov 16;44(20):9530-9554. doi: 10.1093/nar/gkw875. Epub 
      2016 Sep 29.