The Study of the Mouse Schlafen Family Members as Mediators of Antiviral Activity
The Schlafen family of proteins was first characterized in 1988, and since then evidence of their relevance in different physiological and pathological situations have been accumulating although at a slow pace. Hence, the biological roles of these proteins remain ill-defined. The expression of these proteins is positively regulated by type 1 interferons, constituting a component of the innate immune response. Functions of these proteins vary from regulation of cell proliferation to restriction of viral infections. Recent studies have implicated SLFN11 and SLFN13 as inhibitors of HIV-1 infection2-4. The mechanism of action of SLFN11 resides in its capacity to regulate the size of the host tRNA pool, thus counteracting changes in the tRNA repertoire induced by viral infections2,4. However, no relevant cellular models of HIV-1 infection were used to asses this information. Moreover, only one additional report has confirmed the original observations made seven years ago. This situation has fueled doubts in the HIV-1 research community regarding the relevance of SLFN11 anti-HIV-1 mechanism. Importantly, in this work we have validated the tRNase-dependent anti-HIV-1 activity of SLFN11 in human CD4+ T cells and cells of myeloid origin, the main targets of HIV-1 in vivo. Furthermore, we revealed a novel tRNase-independent anti-HIV-1 activity in murine SLFN proteins. These are important contributions to the anti-viral innate immune response field, and they could be exploited in HIV-1 cure strategies.
Hernandez, Julia F, "The Study of the Mouse Schlafen Family Members as Mediators of Antiviral Activity" (2020). ETD Collection for University of Texas, El Paso. AAI27996932.