Implication of TRIM alpha and TRIMCyp in interferon-induced anti-retroviral restriction activities.
BACKGROUND
TRIM5 alpha is a restriction factor that interferes with retroviral infections in a species-specific manner in primate cells. Although TRIM5 alpha is constitutively expressed, its expression has been shown to be up-regulated by type I interferon (IFN). Among primates, a particular case exists in owl monkey cells, which express a fusion protein between TRIM5 and cyclophilin A, TRIMCyp, specifically interfering with HIV-1 infection. No studies have been conducted so far concerning the possible induction of TRIMCyp by IFN. We investigated the consequences of IFN treatment on retroviral restriction in diverse primate cells and evaluated the implication of TRIM5 alpha or TRIMCyp in IFN-induced anti-retroviral activities.


RESULTS
First, we show that human type I IFN can enhance TRIM5 alpha expression in human, African green monkey and macaque cells, as well as TRIMCyp expression in owl monkey cells. In TRIM5 alpha-expressing primate cell lines, type I IFN has little or no effect on HIV-1 infection, whereas it potentiates restriction activity against N-MLV in human and African green monkey cells. In contrast, type I IFN treatment of owl monkey cells induces a great enhancement of HIV-1 restriction, as well as a strain-tropism independent restriction of MLV. We were able to demonstrate that TRIM5 alpha is the main mediator of the IFN-induced activity against N-MLV in human and African green monkey cells, whereas TRIMCyp mediates the IFN-induced HIV-1 restriction enhancement in owl monkey cells. In contrast, the type I IFN-induced anti-MLV restriction in owl monkey cells is independent of TRIMCyp expression.


CONCLUSIONS
Together, our observations indicate that both TRIM5 alpha and TRIMCyp are implicated in IFN-induced anti-retroviral response in primate cells. Furthermore, we found that type I IFN also induces a TRIMCyp-independent restriction activity specific to MLV in owl monkey cells.
Carthagena
Laetitia
L
Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Département des Maladies Infectieuses, 22 rue Méchain, 75014, Paris, France. laetitia.carthagena@inserm.fr
Parise
Mélanie C
MC
Ringeard
Mathieu
M
Chelbi-Alix
Mounira K
MK
Hazan
Uriel
U
Nisole
Sébastien
S
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D000090103:Antiviral Restriction Factors; D001029:Aotus trivirgatus; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002522:Chlorocebus aethiops; D021984:Cyclophilin A / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity; D006367:HeLa Cells; D006801:Humans; D007372:Interferons / Q000494:pharmacology*; D009052:Leukemia Virus, Murine / Q000187:drug effects* / Q000472:pathogenicity; D008253:Macaca mulatta; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D014709:Vero Cells
D000998:Antiviral Agents; D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D000070584:Tripartite Motif Proteins; D007372:Interferons; C477346:TRIM5 protein, human; C482587:TRIM5(alpha) protein, rhesus monkey; D044767:Ubiquitin-Protein Ligases; D021984:Cyclophilin A