PMID- 21908397
OWN - NLM
STAT- MEDLINE
DCOM- 20120227
LR  - 20211020
IS  - 1362-4962 (Electronic)
IS  - 0305-1048 (Print)
IS  - 0305-1048 (Linking)
VI  - 40
IP  - 1
DP  - 2012 Jan
TI  - Biochemical, inhibition and inhibitor resistance studies of xenotropic murine 
      leukemia virus-related virus reverse transcriptase.
PG  - 345-59
LID - 10.1093/nar/gkr694 [doi]
AB  - We report key mechanistic differences between the reverse transcriptases (RT) of 
      human immunodeficiency virus type-1 (HIV-1) and of xenotropic murine leukemia 
      virus-related virus (XMRV), a gammaretrovirus that can infect human cells. Steady 
      and pre-steady state kinetics demonstrated that XMRV RT is significantly less 
      efficient in DNA synthesis and in unblocking chain-terminated primers. Surface 
      plasmon resonance experiments showed that the gammaretroviral enzyme has a 
      remarkably higher dissociation rate (k(off)) from DNA, which also results in 
      lower processivity than HIV-1 RT. Transient kinetics of mismatch incorporation 
      revealed that XMRV RT has higher fidelity than HIV-1 RT. We identified RNA 
      aptamers that potently inhibit XMRV, but not HIV-1 RT. XMRV RT is highly 
      susceptible to some nucleoside RT inhibitors, including Translocation Deficient 
      RT inhibitors, but not to non-nucleoside RT inhibitors. We demonstrated that XMRV 
      RT mutants K103R and Q190M, which are equivalent to HIV-1 mutants that are 
      resistant to tenofovir (K65R) and AZT (Q151M), are also resistant to the 
      respective drugs, suggesting that XMRV can acquire resistance to these compounds 
      through the decreased incorporation mechanism reported in HIV-1.
FAU - Ndongwe, Tanyaradzwa P
AU  - Ndongwe TP
AD  - Christopher Bond Life Sciences Center, Department of Molecular Microbiology & 
      Immunology, University of Missouri, School of Medicine, Columbia, MO 65211, USA.
FAU - Adedeji, Adeyemi O
AU  - Adedeji AO
FAU - Michailidis, Eleftherios
AU  - Michailidis E
FAU - Ong, Yee Tsuey
AU  - Ong YT
FAU - Hachiya, Atsuko
AU  - Hachiya A
FAU - Marchand, Bruno
AU  - Marchand B
FAU - Ryan, Emily M
AU  - Ryan EM
FAU - Rai, Devendra K
AU  - Rai DK
FAU - Kirby, Karen A
AU  - Kirby KA
FAU - Whatley, Angela S
AU  - Whatley AS
FAU - Burke, Donald H
AU  - Burke DH
FAU - Johnson, Marc
AU  - Johnson M
FAU - Ding, Shilei
AU  - Ding S
FAU - Zheng, Yi-Min
AU  - Zheng YM
FAU - Liu, Shan-Lu
AU  - Liu SL
FAU - Kodama, Ei-Ichi
AU  - Kodama E
FAU - Delviks-Frankenberry, Krista A
AU  - Delviks-Frankenberry KA
FAU - Pathak, Vinay K
AU  - Pathak VK
FAU - Mitsuya, Hiroaki
AU  - Mitsuya H
FAU - Parniak, Michael A
AU  - Parniak MA
FAU - Singh, Kamalendra
AU  - Singh K
FAU - Sarafianos, Stefan G
AU  - Sarafianos SG
LA  - eng
GR  - AI079801/AI/NIAID NIH HHS/United States
GR  - AI076119/AI/NIAID NIH HHS/United States
GR  - R01 AI073098/AI/NIAID NIH HHS/United States
GR  - R25 GM056901/GM/NIGMS NIH HHS/United States
GR  - CAPMC/CIHR/Canada
GR  - AI094715/AI/NIAID NIH HHS/United States
GR  - AI074389/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110908
PL  - England
TA  - Nucleic Acids Res
JT  - Nucleic acids research
JID - 0411011
RN  - 0 (Aptamers, Nucleotide)
RN  - 0 (Nucleotides)
RN  - 0 (Organophosphonates)
RN  - 0 (Reverse Transcriptase Inhibitors)
RN  - 4B9XT59T7S (Zidovudine)
RN  - 9007-49-2 (DNA)
RN  - 99YXE507IL (Tenofovir)
RN  - EC 2.7.7.- (reverse transcriptase, Human immunodeficiency virus 1)
RN  - EC 2.7.7.49 (HIV Reverse Transcriptase)
RN  - EC 2.7.7.49 (RNA-Directed DNA Polymerase)
RN  - EC 3.2.1.23 (beta-Galactosidase)
RN  - JAC85A2161 (Adenine)
SB  - IM
MH  - Adenine/analogs & derivatives/pharmacology
MH  - Amino Acid Sequence
MH  - Aptamers, Nucleotide/pharmacology
MH  - DNA/biosynthesis/metabolism
MH  - HIV Reverse Transcriptase/*chemistry/genetics/*metabolism
MH  - Kinetics
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Moloney murine leukemia virus/enzymology
MH  - Mutation
MH  - Nucleotides/metabolism
MH  - Organophosphonates/pharmacology
MH  - RNA-Directed DNA Polymerase/*chemistry/genetics/*metabolism
MH  - Reverse Transcriptase Inhibitors/pharmacology
MH  - Sequence Homology, Amino Acid
MH  - Tenofovir
MH  - Xenotropic murine leukemia virus-related virus/*enzymology
MH  - Zidovudine/pharmacology
MH  - beta-Galactosidase/genetics
PMC - PMC3245923
EDAT- 2011/09/13 06:00
MHDA- 2012/03/01 06:00
PMCR- 2011/09/08
CRDT- 2011/09/13 06:00
PHST- 2011/09/13 06:00 [entrez]
PHST- 2011/09/13 06:00 [pubmed]
PHST- 2012/03/01 06:00 [medline]
PHST- 2011/09/08 00:00 [pmc-release]
AID - gkr694 [pii]
AID - 10.1093/nar/gkr694 [doi]
PST - ppublish
SO  - Nucleic Acids Res. 2012 Jan;40(1):345-59. doi: 10.1093/nar/gkr694. Epub 2011 Sep 
      8.