PMID- 25965791
OWN - NLM
STAT- MEDLINE
DCOM- 20151012
LR  - 20150727
IS  - 1096-0341 (Electronic)
IS  - 0042-6822 (Linking)
VI  - 483
DP  - 2015 Sep
TI  - The importance of glutamine 294 that affects the ribonuclease H activity of the 
      reverse transcriptase of HIV-2 to viral replication.
PG  - 13-20
LID - S0042-6822(15)00229-9 [pii]
LID - 10.1016/j.virol.2015.04.018 [doi]
AB  - Most currently-used antiretroviral drugs inhibit the reverse-transcriptase (RT) 
      of HIV. The differences between HIV-1 and HIV-2 RTs explain why some of the 
      anti-HIV-1 drugs are not effective against HIV-2. One major difference between 
      the two HIV RTs is the low ribonuclease H (RNase H) activity of HIV-2 RT relative 
      to HIV-1 RT. Our previous studies showed that residue Gln294 in HIV-2 RT accounts 
      for this RNase H reduction (the comparable residue in HIV-1 RT is Pro294), as the 
      Q294P mutant of HIV-2 RT has ~10-fold higher RNase H. Here, we show that 
      infectious HIV-2 cannot bear the replacement of the RT's Gln294 by the HIV-1 RT 
      Pro counterpart, as it results in substantially reduced HIV-2 replication and 
      fast reversions to the wild-type Gln294 virus. These findings prove the critical 
      role of maintaining low RT-associated RNase H activity in HIV-2. In contrast, 
      HIV-1 can tolerate an about 10-fold higher RNase H.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Herzig, Eytan
AU  - Herzig E
AD  - Department of Cell and Developmental Biology, Sackler School of Medicine, Tel 
      Aviv University, Tel Aviv 69974, Israel.
FAU - Hizi, Amnon
AU  - Hizi A
AD  - Department of Cell and Developmental Biology, Sackler School of Medicine, Tel 
      Aviv University, Tel Aviv 69974, Israel. Electronic address: 
      ahizy@post.tau.ac.il.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150515
PL  - United States
TA  - Virology
JT  - Virology
JID - 0110674
RN  - 0 (Mutant Proteins)
RN  - 0RH81L854J (Glutamine)
RN  - EC 2.7.7.49 (RNA-Directed DNA Polymerase)
RN  - EC 3.1.26.4 (Ribonuclease H)
SB  - IM
MH  - Amino Acid Substitution
MH  - Glutamine/genetics/*metabolism
MH  - HIV-2/*enzymology/*physiology
MH  - Humans
MH  - Mutant Proteins/genetics/metabolism
MH  - Mutation, Missense
MH  - RNA-Directed DNA Polymerase/genetics/*metabolism
MH  - Reverse Transcription
MH  - Ribonuclease H/genetics/*metabolism
MH  - *Virus Replication
OTO - NOTNLM
OT  - HIV-1
OT  - HIV-2
OT  - Q294P HIV-2 RT mutation
OT  - RNase H
OT  - Reverse transcriptase
OT  - Reverse transcription
OT  - Reversions
OT  - Virus replication
EDAT- 2015/05/13 06:00
MHDA- 2015/10/13 06:00
CRDT- 2015/05/13 06:00
PHST- 2015/01/25 00:00 [received]
PHST- 2015/04/02 00:00 [revised]
PHST- 2015/04/13 00:00 [accepted]
PHST- 2015/05/13 06:00 [entrez]
PHST- 2015/05/13 06:00 [pubmed]
PHST- 2015/10/13 06:00 [medline]
AID - S0042-6822(15)00229-9 [pii]
AID - 10.1016/j.virol.2015.04.018 [doi]
PST - ppublish
SO  - Virology. 2015 Sep;483:13-20. doi: 10.1016/j.virol.2015.04.018. Epub 2015 May 15.