High levels of trim5a are associated with xenophagy in hiv‐1‐infected long‐term nonprogressors

Autophagy is a lysosomal‐dependent degradative mechanism essential in maintaining cellular homeostasis, but it is also considered an ancient form of innate eukaryotic fighting against invading microorganisms. Mounting evidence has shown that HIV‐1 is a critical target of autoph-agy that plays a role in HIV‐1 replication and disease progression. In a special subset of HIV‐1‐infected patients that spontaneously and durably maintain extremely low viral replication, namely, long‐term nonprogressors (LTNP), the resistance to HIV‐1‐induced pathogenesis is ac-companied, in vivo, by a significant increase in the autophagic activity in peripheral blood mon-onuclear cells. Recently, a new player in the battle of autophagy against HIV‐1 has been identified, namely, tripartite motif protein 5α (TRIM5α). In vitro data demonstrated that TRIM5α directly recognizes HIV‐1 and targets it for autophagic destruction, thus protecting cells against HIV‐1 in-fection. In this paper, we analyzed the involvement of this factor in the control of HIV‐1 infection through autophagy, in vivo, in LTNP. The results obtained showed significantly higher levels of TRIM5α expression in cells from LTNP with respect to HIV‐1‐infected normal progressor patients. Interestingly, the colocalization of TRIM5α and HIV‐1 proteins in autophagic vacuoles in LTNP cells suggested the participation of TRIM5α in the autophagy containment of HIV‐1 in LTNP. Al-together, our results point to a protective role of TRIM5α in the successful control of the chronic viral infection in HIV‐1‐controllers through the autophagy mechanism. In our opinion, these findings could be relevant in fighting against HIV‐1 disease, because autophagy inducers might be employed in combination with antiretroviral drugs.