PMID- 23000900
OWN - NLM
STAT- MEDLINE
DCOM- 20121226
LR  - 20211021
IS  - 1476-4687 (Electronic)
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 491
IP  - 7422
DP  - 2012 Nov 1
TI  - Codon-usage-based inhibition of HIV protein synthesis by human schlafen 11.
PG  - 125-8
LID - 10.1038/nature11433 [doi]
AB  - In mammals, one of the most pronounced consequences of viral infection is the 
      induction of type I interferons, cytokines with potent antiviral activity. 
      Schlafen (Slfn) genes are a subset of interferon-stimulated early response genes 
      (ISGs) that are also induced directly by pathogens via the interferon regulatory 
      factor 3 (IRF3) pathway. However, many ISGs are of unknown or incompletely 
      understood function. Here we show that human SLFN11 potently and specifically 
      abrogates the production of retroviruses such as human immunodeficiency virus 1 
      (HIV-1). Our study revealed that SLFN11 has no effect on the early steps of the 
      retroviral infection cycle, including reverse transcription, integration and 
      transcription. Rather, SLFN11 acts at the late stage of virus production by 
      selectively inhibiting the expression of viral proteins in a 
      codon-usage-dependent manner. We further find that SLFN11 binds transfer RNA, and 
      counteracts changes in the tRNA pool elicited by the presence of HIV. Our studies 
      identified a novel antiviral mechanism within the innate immune response, in 
      which SLFN11 selectively inhibits viral protein synthesis in HIV-infected cells 
      by means of codon-bias discrimination.
FAU - Li, Manqing
AU  - Li M
AD  - Section of Molecular Biology, Division of Biological Sciences, University of 
      California San Diego, La Jolla, California 92093, USA.
FAU - Kao, Elaine
AU  - Kao E
FAU - Gao, Xia
AU  - Gao X
FAU - Sandig, Hilary
AU  - Sandig H
FAU - Limmer, Kirsten
AU  - Limmer K
FAU - Pavon-Eternod, Mariana
AU  - Pavon-Eternod M
FAU - Jones, Thomas E
AU  - Jones TE
FAU - Landry, Sebastien
AU  - Landry S
FAU - Pan, Tao
AU  - Pan T
FAU - Weitzman, Matthew D
AU  - Weitzman MD
FAU - David, Michael
AU  - David M
LA  - eng
GR  - R21 AI081019/AI/NIAID NIH HHS/United States
GR  - AI074967/AI/NIAID NIH HHS/United States
GR  - P01AI090935/AI/NIAID NIH HHS/United States
GR  - P30AI36214/AI/NIAID NIH HHS/United States
GR  - R21AI088490/AI/NIAID NIH HHS/United States
GR  - R01GM101982/GM/NIGMS NIH HHS/United States
GR  - R21 AI088490/AI/NIAID NIH HHS/United States
GR  - AI81019/AI/NIAID NIH HHS/United States
GR  - P30 AI036214/AI/NIAID NIH HHS/United States
GR  - R01 GM101982/GM/NIGMS NIH HHS/United States
GR  - R01 AI074967/AI/NIAID NIH HHS/United States
GR  - P01 AI090935/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120923
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Codon)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA, Viral)
RN  - 0 (SLFN11 protein, human)
RN  - 0 (Viral Proteins)
RN  - 9014-25-9 (RNA, Transfer)
SB  - IM
CIN - Nat Rev Urol. 2012 Nov;9(11):605. PMID: 23045266
CIN - Nat Rev Microbiol. 2012 Nov;10(11):732. PMID: 23070553
MH  - Cell Line
MH  - Cells, Cultured
MH  - Codon/*genetics/immunology
MH  - Gene Expression Regulation, Viral/*genetics
MH  - HEK293 Cells
MH  - HIV-1/*genetics/growth & development/immunology/metabolism
MH  - Humans
MH  - Immunity, Innate
MH  - Nuclear Proteins/immunology/*metabolism
MH  - Protein Biosynthesis/*genetics/immunology
MH  - RNA, Transfer/genetics/metabolism
MH  - RNA, Viral/genetics/metabolism
MH  - Reverse Transcription
MH  - Species Specificity
MH  - Substrate Specificity
MH  - Viral Proteins/*biosynthesis/*genetics
MH  - Virus Integration
PMC - PMC3705913
MID - NIHMS475634
COIS- The authors declare no competing financial interests.
EDAT- 2012/09/25 06:00
MHDA- 2012/12/27 06:00
PMCR- 2013/11/01
CRDT- 2012/09/25 06:00
PHST- 2011/11/22 00:00 [received]
PHST- 2012/07/23 00:00 [accepted]
PHST- 2012/09/25 06:00 [entrez]
PHST- 2012/09/25 06:00 [pubmed]
PHST- 2012/12/27 06:00 [medline]
PHST- 2013/11/01 00:00 [pmc-release]
AID - nature11433 [pii]
AID - 10.1038/nature11433 [doi]
PST - ppublish
SO  - Nature. 2012 Nov 1;491(7422):125-8. doi: 10.1038/nature11433. Epub 2012 Sep 23.