[Cellular and antiviral functions of TRIM5α]

In this review, we summarize recent advances in the knowledge of the biological functions of human TRIM5α, a cytoplasmic protein mostly known for its antiretroviral functions. In addition to directly targeting retroviral capsid cores, an inhibitory activity called "restriction", TRIM5α senses retroviruses and activates NF-κB and AP-1 signaling pathways, resulting in the production of type I interferon (IFN-I). The antiviral state resulting from the activation of these pathways includes the upregulation of other restriction factors, and is thought to be important for the control of HIV-1 in some patients. TRIM5α also targets the protease enzyme of several tick-borne flaviviruses, a family of viruses not closely related to retroviruses. In addition to these antiviral functions, TRIM5α promotes autophagy by interacting with key actors of this pathway, such as ULK1 and p62. TRIM5α may function as a selective autophagy receptor in some conditions. Altogether, our understanding of TRIM5α shows its potential for the development of medical applications in viral diseases and beyond.