IFI44L expression is regulated by IRF-1 and HIV-1

Interferon (IFN)-inducible 44 like (IFI44L) is an IFN-stimulated gene (ISG), which is located on the same chromosome as the known antiviral ISG IFI44. Expression of IFI44L is induced by IFN and HIV-1 infection. However, the mechanism by which IFN-I induces IFI44L production has not yet been determined. In this study, we analyzed transcriptional regulation of IFI44L via cloning of the IFI44L promoter. We found that IFI44L has two IFN-stimulated response elements (ISRE), which are necessary for the basal level of IFI44L transcription. IFN-I and IFN-II can activate the IFI44L promoter through one of the two ISREs. IFN regulatory factor (IRF)-1 can activate transcription of IFI44L by binding to one of the ISREs. Additionally, co-transfection of the IFI44L promoter with an HIV-1 infectious clone or HIV-1 infection activated IFI44L promoter transcription, but did not upregulate IFI44L expression via ISREs. These findings will help to understand the interaction between IFI44L and HIV-1, and aid in elucidation of the role of IFI44L in the antiviral innate immune response.