The cellular factor TRIM5α performs a dual role in the innate immunity. First, TRIM5α has an intrinsic ability to induce the AP-1 and NFκB pathways and contributes to the establishment of the LPS-mediated antiviral state. Second, it functions as a restriction factor, blocking early stages of retroviral infection in a capsid-dependent manner. The connections between these two functions of TRIM5α are debated. We investigated the conservation, in TRIM5 orthologues, of the ability to activate the innate immune pathways and analyzed the signification of this function in the context of TRIM5- mediated HIV-1 restriction. We took the advantage that there are seven TRIM5 orthologues in the mouse, with variable abilities to activate the innate immune signaling, to determine the contribution of this signal activator function to the restriction process. [...]