The innate immune system is the first line of defense that all organisms developed to fight against incoming pathogen. Specific cellular receptors, called Pattern Recognition Receptors (PRRs) detect non-self molecules and induce a signaling cascade that allows the cell to fight the pathogen. In this work we focus on the detection of Human Immunodeficiency Virus 1 (HIV-1) and on the activation and regulation of a class of PRRs: the RIG-I Like Receptors family (RLRs). We were able to demonstrate that the cellular restriction factor TRIM5 is a PRR for the incoming retroviral capsid lattice and that upon its recognition induce a cascade, which contribute to the restriction of the virus. On the other side we propose a new molecular mechanism of regulation of the pioneer member of the RLRs, RIG-I, by LGP2. We demonstrate that LGP2 negatively interferes with RIG-I activation by enhancing its recycling on the RNA.