PMID- 22114335
OWN - NLM
STAT- MEDLINE
DCOM- 20120409
LR  - 20240412
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 86
IP  - 3
DP  - 2012 Feb
TI  - RING domain mutations uncouple TRIM5alpha restriction of HIV-1 from inhibition of 
      reverse transcription and acceleration of uncoating.
PG  - 1717-27
LID - 10.1128/JVI.05811-11 [doi]
AB  - Rhesus TRIM5alpha (TRIM5alpha(rh)) is a cytosolic protein that potently restricts HIV-1 
      at an early postentry stage, prior to reverse transcription. The ability of 
      TRIM5alpha(rh) to block HIV-1 infection has been correlated with a decrease of 
      pelletable HIV-1 capsid during infection. To genetically dissect the ability of 
      TRIM5alpha to block reverse transcription, we studied a set of TRIM5alpha(rh) RING domain 
      mutants that potently restrict HIV-1 but allow the occurrence of reverse 
      transcription. These TRIM5alpha(rh) RING variants blocked HIV-1 infection after 
      reverse transcription but prior to integration, as suggested by the routing of 
      nuclear viral DNA to circularization in the form of 2-long terminal repeat 
      (2-LTR) circles. The folding of RING domain variants was similar to that of the 
      wild type, as evaluated by nuclear magnetic resonance. RING domain changes that 
      allowed the occurrence of reverse transcription were impaired in their ability to 
      decrease the amount of pelletable capsid compared with wild-type TRIM5alpha. Similar 
      effects of this particular group of mutations were observed with human TRIM5alpha 
      inhibition of N-tropic murine leukemia virus (N-MLV). Interestingly, TRIM5alpha(rh) 
      RING domain variants also prevented the degradation of TRIM5alpha(rh) that occurs 
      following cell entry of HIV-1. These data correlated the block of reverse 
      transcription with the ability of TRIM5alpha to accelerate uncoating. Collectively, 
      these results suggest that TRIM5alpha(rh) blocks HIV-1 reverse transcription by 
      inducing premature viral uncoating in target cells.
FAU - Roa, Amanda
AU  - Roa A
AD  - Department of Microbiology and Immunology, Albert Einstein College of Medicine 
      Bronx, New York, USA.
FAU - Hayashi, Fumiaki
AU  - Hayashi F
FAU - Yang, Yang
AU  - Yang Y
FAU - Lienlaf, Maritza
AU  - Lienlaf M
FAU - Zhou, Jing
AU  - Zhou J
FAU - Shi, Jiong
AU  - Shi J
FAU - Watanabe, Satoru
AU  - Watanabe S
FAU - Kigawa, Takanori
AU  - Kigawa T
FAU - Yokoyama, Shigeyuki
AU  - Yokoyama S
FAU - Aiken, Christopher
AU  - Aiken C
FAU - Diaz-Griffero, Felipe
AU  - Diaz-Griffero F
LA  - eng
GR  - R00 MH086162/MH/NIMH NIH HHS/United States
GR  - R01 AI076121/AI/NIAID NIH HHS/United States
GR  - R01 AI087390/AI/NIAID NIH HHS/United States
GR  - 4R00MH086162-02/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20111123
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Antiviral Restriction Factors)
RN  - 0 (Carrier Proteins)
RN  - 0 (DNA Probes)
RN  - 0 (Proteins)
RN  - 0 (Tripartite Motif Proteins)
RN  - EC 2.3.2.27 (TRIM5 protein, human)
RN  - EC 2.3.2.27 (TRIM5(alpha) protein, rhesus monkey)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
SB  - IM
MH  - Animals
MH  - Antiviral Restriction Factors
MH  - Base Sequence
MH  - Carrier Proteins/genetics/*metabolism
MH  - Cell Line
MH  - DNA Probes
MH  - Dogs
MH  - HIV Long Terminal Repeat
MH  - HIV-1/*physiology
MH  - Humans
MH  - *Mutation
MH  - Nuclear Magnetic Resonance, Biomolecular
MH  - Proteins/chemistry/genetics/*metabolism
MH  - Real-Time Polymerase Chain Reaction
MH  - Reverse Transcription
MH  - Thymocytes/virology
MH  - *Transcription, Genetic
MH  - Tripartite Motif Proteins
MH  - Ubiquitin-Protein Ligases
MH  - Virus Uncoating
PMC - PMC3264337
EDAT- 2011/11/25 06:00
MHDA- 2012/04/10 06:00
PMCR- 2012/08/01
CRDT- 2011/11/25 06:00
PHST- 2011/11/25 06:00 [entrez]
PHST- 2011/11/25 06:00 [pubmed]
PHST- 2012/04/10 06:00 [medline]
PHST- 2012/08/01 00:00 [pmc-release]
AID - JVI.05811-11 [pii]
AID - 5811-11 [pii]
AID - 10.1128/JVI.05811-11 [doi]
PST - ppublish
SO  - J Virol. 2012 Feb;86(3):1717-27. doi: 10.1128/JVI.05811-11. Epub 2011 Nov 23.