PMID- 18448538
OWN - NLM
STAT- MEDLINE
DCOM- 20080806
LR  - 20231213
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 82
IP  - 13
DP  - 2008 Jul
TI  - Comparison of G-to-A mutation frequencies induced by APOBEC3 proteins in H9 cells 
      and peripheral blood mononuclear cells in the context of impaired processivities 
      of drug-resistant human immunodeficiency virus type 1 reverse transcriptase 
      variants.
PG  - 6536-45
LID - 10.1128/JVI.00554-08 [doi]
AB  - APOBEC3 proteins can inhibit human immunodeficiency virus type 1 (HIV-1) 
      replication by inducing G-to-A mutations in newly synthesized viral DNA. However, 
      HIV-1 is able to overcome the antiretroviral activity of some of those enzymes by 
      the viral protein Vif. We investigated the impact of different processivities of 
      HIV-1 reverse transcriptases (RT) on the frequencies of G-to-A mutations 
      introduced by APOBEC3 proteins. Wild-type RT or the M184V, M184I, and K65R+M184V 
      RT variants, which are increasingly impaired in their processivities, were used 
      in the context of a vif-deficient molecular HIV-1 clone to infect H9 cells and 
      peripheral blood mononuclear cells (PBMCs). After two rounds of infection, a part 
      of the HIV-1 env gene was amplified, cloned, and sequenced. The M184V mutation 
      led to G-to-A mutation frequencies that were similar to those of the wild-type RT 
      in H9 cells and PBMCs. The frequencies of G-to-A mutations were increased after 
      infection with the M184I virus variant. This effect was augmented when using the 
      K65R+M184V virus variant (P < 0.001). Overall, the G-to-A mutation frequencies 
      were lower in PBMCs than in H9 cells. Remarkably, 38% +/- 18% (mean +/- standard 
      deviation) of the env clones derived from PBMCs did not harbor any G-to-A 
      mutation. This was rarely observed in H9 cells (3% +/- 3%). Our data imply that 
      the frequency of G-to-A mutations induced by APOBEC3 proteins can be influenced 
      by the processivities of HIV-1 RT variants. The high number of nonmutated clones 
      derived from PBMCs leads to several hypotheses, including that additional 
      antiretroviral mechanisms of APOBEC3 proteins other than their deamination 
      activity might be involved in the inhibition of vif-deficient viruses.
FAU - Knoepfel, Stefanie Andrea
AU  - Knoepfel SA
AD  - University of Erlangen-Nuremberg, Institute of Clinical and Molecular Virology, 
      Schlossgarten 4, 91054 Erlangen, Germany.
FAU - Salisch, Nadine Christina
AU  - Salisch NC
FAU - Huelsmann, Peter Michael
AU  - Huelsmann PM
FAU - Rauch, Pia
AU  - Rauch P
FAU - Walter, Hauke
AU  - Walter H
FAU - Metzner, Karin Jutta
AU  - Metzner KJ
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080430
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (DNA Primers)
RN  - 0 (env Gene Products, Human Immunodeficiency Virus)
RN  - EC 2.7.7.- (reverse transcriptase, Human immunodeficiency virus 1)
RN  - EC 2.7.7.49 (HIV Reverse Transcriptase)
RN  - EC 3.5.4.1 (Cytosine Deaminase)
RN  - EC 3.5.4.5 (APOBEC Deaminases)
RN  - EC 3.5.4.5 (APOBEC3 proteins, human)
RN  - EC 3.5.4.5 (Cytidine Deaminase)
SB  - IM
MH  - APOBEC Deaminases
MH  - Base Sequence
MH  - Cell Line
MH  - Cytidine Deaminase
MH  - Cytosine Deaminase/*metabolism
MH  - DNA Primers/genetics
MH  - HIV Reverse Transcriptase/*genetics
MH  - HIV-1/*genetics/metabolism
MH  - Humans
MH  - Leukocytes, Mononuclear
MH  - Molecular Sequence Data
MH  - Mutation/*genetics
MH  - Sequence Analysis, DNA
MH  - env Gene Products, Human Immunodeficiency Virus/*genetics
PMC - PMC2447050
EDAT- 2008/05/02 09:00
MHDA- 2008/08/07 09:00
PMCR- 2008/11/01
CRDT- 2008/05/02 09:00
PHST- 2008/05/02 09:00 [pubmed]
PHST- 2008/08/07 09:00 [medline]
PHST- 2008/05/02 09:00 [entrez]
PHST- 2008/11/01 00:00 [pmc-release]
AID - JVI.00554-08 [pii]
AID - 0554-08 [pii]
AID - 10.1128/JVI.00554-08 [doi]
PST - ppublish
SO  - J Virol. 2008 Jul;82(13):6536-45. doi: 10.1128/JVI.00554-08. Epub 2008 Apr 30.