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.
Conclusion: 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.