SLFN14 functions as a P-TEFb inhibitor to modulate the transcription of HIV-1 and cellular genes.

The Schlafen (SLFN) gene family encodes different growth regulatory factors known to participate in cell growth, differentiation, tumorigenesis, and the immune response against virus infection. However, the molecular mechanisms underlying their functions remain largely incomplete. In this study, we report that the SLFN family member SLFN14 has potent anti-HIV-1 activity. Specifically, SLFN14 binds to the positive transcription elongation factor b (P-TEFb), thereby preventing HIV-1 Tat-mediated recruitment of P-TEFb to the HIV-1 promoter and causing an arrest of viral transcription. Furthermore, this P-TEFb-targeted inhibiting activity also allows SLFN14 to regulate the transcription of a subset of cellular genes. Thus, our data identify SLFN14 as an inhibitor of the important transcription elongation factor P-TEFb complex, which unveils the crucial role of SLFN14 in both cellular antiviral defense and other important cellular processes that rely on the function of this complex.