PMID- 17892575
OWN - NLM
STAT- MEDLINE
DCOM- 20080204
LR  - 20191210
IS  - 1742-4690 (Electronic)
IS  - 1742-4690 (Linking)
VI  - 4
DP  - 2007 Sep 24
TI  - Both TRIM5alpha and TRIMCyp have only weak antiviral activity in canine D17 
      cells.
PG  - 68
AB  - BACKGROUND: TRIM5alpha, which is expressed in most primates and the related 
      TRIMCyp, which has been found in one of the New World monkey species, are 
      antiviral proteins of the TRIM5 family that are able to intercept incoming 
      retroviruses early after their entry into cells. The mechanism of action has been 
      partially elucidated for TRIM5alpha, which seems to promote premature 
      decapsidation of the restricted retroviruses. In addition, through its N-terminal 
      RING domain, TRIM5alpha may sensitize retroviruses to proteasome-mediated 
      degradation. TRIM5alpha-mediated restriction requires a physical interaction with 
      the capsid protein of targeted retroviruses. It is unclear whether other cellular 
      proteins are involved in the inhibition mediated by TRIM5alpha and TRIMCyp. A 
      previous report suggested that the inhibition of HIV-1 by the rhesus macaque 
      orthologue of TRIM5alpha was inefficient in the D17a canine cell line, suggesting 
      that the cellular environment was important for the restriction mechanism. Here 
      we investigated further the behavior of TRIM5alpha and TRIMCyp in the D17 cells. 
      RESULTS: We found that the various TRIM5alpha orthologues studied (human, rhesus 
      macaque, African green monkey) as well as TRIMCyp had poor antiviral activity in 
      the D17 cells, despite seemingly normal expression levels and subcellular 
      distribution. Restriction of both HIV-1 and the distantly related N-tropic murine 
      leukemia virus (N-MLV) was low in D17 cells. Both TRIM5alpharh and TRIMCyp 
      promoted early HIV-1 decapsidation in murine cells, but weak levels of 
      restriction in D17 cells correlated with the absence of accelerated decapsidation 
      in these cells and also correlated with normal levels of cDNA synthesis. Fv1, a 
      murine restriction factor structurally unrelated to TRIM5alpha, was fully 
      functional in D17 cells, showing that the loss of activity was specific to 
      TRIM5alpha/TRIMCyp. CONCLUSION: We show that D17 cells provide a poor environment 
      for the inhibition of retroviral replication by proteins of the TRIM5 family. 
      Because both TRIM5alpha and TRIMCyp are poorly active in these cells, despite 
      having quite different viral target recognition domains, we conclude that a step 
      either upstream or downstream of target recognition is impaired. We speculate 
      that an unknown factor required for TRIM5alpha and TRIMCyp activity is missing or 
      inadequately expressed in D17 cells.
FAU - Berube, Julie
AU  - Berube J
AD  - Laboratory of Retrovirology, GRBCM, University of Quebec, Trois-Rivieres, QC G9A 
      5H7, Canada. julie.berube1@uqtr.ca
FAU - Bouchard, Amelie
AU  - Bouchard A
FAU - Berthoux, Lionel
AU  - Berthoux L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070924
PL  - England
TA  - Retrovirology
JT  - Retrovirology
JID - 101216893
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Antiviral Agents)
RN  - 0 (Proteins)
RN  - EC 2.3.2.27 (TRIM5(alpha) protein, rhesus monkey)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 5.2.1.- (Cyclophilin A)
SB  - IM
MH  - Animals
MH  - Anti-HIV Agents/pharmacology
MH  - Antiviral Agents/*pharmacology
MH  - Cell Line
MH  - Cyclophilin A/genetics/*metabolism
MH  - Dogs
MH  - HIV-1/*drug effects
MH  - Leukemia Virus, Murine/*drug effects/pathogenicity
MH  - Proteins/*pharmacology
MH  - Ubiquitin-Protein Ligases
PMC - PMC2064933
EDAT- 2007/09/26 09:00
MHDA- 2008/02/05 09:00
PMCR- 2007/09/24
CRDT- 2007/09/26 09:00
PHST- 2007/06/19 00:00 [received]
PHST- 2007/09/24 00:00 [accepted]
PHST- 2007/09/26 09:00 [pubmed]
PHST- 2008/02/05 09:00 [medline]
PHST- 2007/09/26 09:00 [entrez]
PHST- 2007/09/24 00:00 [pmc-release]
AID - 1742-4690-4-68 [pii]
AID - 10.1186/1742-4690-4-68 [doi]
PST - epublish
SO  - Retrovirology. 2007 Sep 24;4:68. doi: 10.1186/1742-4690-4-68.