PMID- 16501094
OWN - NLM
STAT- MEDLINE
DCOM- 20060405
LR  - 20240413
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 80
IP  - 6
DP  - 2006 Mar
TI  - Cyclophilin A and TRIM5alpha independently regulate human immunodeficiency virus 
      type 1 infectivity in human cells.
PG  - 2855-62
AB  - Cyclophilin A (CypA), a cytoplasmic, human immunodeficiency virus type 1 (HIV-1) 
      CA-binding protein, acts after virion membrane fusion with human cells to 
      increase HIV-1 infectivity. HIV-1 CA is similarly greeted by CypA soon after 
      entry into rhesus macaque or African green monkey cells, where, paradoxically, 
      the interaction decreases HIV-1 infectivity by facilitating TRIM5alpha-mediated 
      restriction. These observations conjure a model in which CA recognition by the 
      human TRIM5alpha orthologue is precluded by CypA. Consistent with the model, 
      selection of a human cell line for decreased restriction of the 
      TRIM5alpha-sensitive, N-tropic murine leukemia virus (N-MLV) rendered HIV-1 
      transduction of these cells independent of CypA. Additionally, HIV-1 virus-like 
      particles (VLPs) saturate N-MLV restriction activity, particularly when the 
      CA-CypA interaction is disrupted. Here the effects of CypA and TRIM5alpha on 
      HIV-1 restriction were examined directly. RNA interference was used to show that 
      endogenous human TRIM5alpha does indeed restrict HIV-1, but the magnitude of this 
      antiviral activity was not altered by disruption of the CA-CypA interaction or by 
      elimination of CypA protein. Conversely, the stimulatory effect of CypA on HIV-1 
      infectivity was completely independent of human TRIM5alpha. Together with 
      previous reports, these data suggest that CypA protects HIV-1 from an unknown 
      antiviral activity in human cells. Additionally, target cell permissivity 
      increased after loading with heterologous VLPs, consistent with a common 
      saturable target that is epistatic to both TRIM5alpha and the putative 
      CypA-regulated restriction factor.
FAU - Sokolskaja, Elena
AU  - Sokolskaja E
AD  - Department of Microbiology, Columbia University, 701 West 168th Street, New York, 
      New York 10032, USA.
FAU - Berthoux, Lionel
AU  - Berthoux L
FAU - Luban, Jeremy
AU  - Luban J
LA  - eng
GR  - R01 AI036199/AI/NIAID NIH HHS/United States
GR  - R01AI36199/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Antiviral Restriction Factors)
RN  - 0 (Carrier Proteins)
RN  - 0 (Tripartite Motif Proteins)
RN  - EC 2.3.2.27 (TRIM5 protein, human)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 5.2.1.- (Cyclophilin A)
SB  - IM
MH  - Antiviral Restriction Factors
MH  - Carrier Proteins/genetics/*metabolism
MH  - Cell Line
MH  - Cyclophilin A/genetics/*metabolism
MH  - HIV-1/genetics/*pathogenicity/physiology
MH  - HeLa Cells
MH  - Humans
MH  - RNA Interference
MH  - Tripartite Motif Proteins
MH  - Ubiquitin-Protein Ligases
MH  - Virion/metabolism
MH  - Virus Replication
PMC - PMC1395419
EDAT- 2006/02/28 09:00
MHDA- 2006/04/06 09:00
PMCR- 2006/07/01
CRDT- 2006/02/28 09:00
PHST- 2006/02/28 09:00 [pubmed]
PHST- 2006/04/06 09:00 [medline]
PHST- 2006/02/28 09:00 [entrez]
PHST- 2006/07/01 00:00 [pmc-release]
AID - 80/6/2855 [pii]
AID - 0604-05 [pii]
AID - 10.1128/JVI.80.6.2855-2862.2006 [doi]
PST - ppublish
SO  - J Virol. 2006 Mar;80(6):2855-62. doi: 10.1128/JVI.80.6.2855-2862.2006.