Research Projects

SERINC5 is a multipass transmembrane protein identified as a restriction factor against Nef-defective HIV-1(Rosa et al., 2015; Usami et al., 2015), and more recently against Classical swine fever virus (CSFV) (Li et al., 2020) and Hepatitis B (Liu et al., 2020). With more reports coming in light, novel roles of this host factor in viral infection are being identified, including its ability to induce an innate immune response. However, the mechanisms of viral infection inhibition by SERINC5 have multiple premises and its cellular functions are yet to be resolved. Considering its recently identified role in innate immune signaling(Zeng et al., 2021) and induction of pro-inflammatory cytokines (Pierini et al., 2021), we surmised that SERINC5 must be regulating more pathways since factors directly involved in signaling are inevitably a part of alternate responses or a consequential response to stimulus. Interestingly, with focused investigation, we did indeed observe that SERINC5 affects a yet-undefined pathway via the transcription factor, NFAT. Moreover, in an independent investigation to identify antiviral roles of SERINC5 in cells of differing tissue origins, we encountered a cell type-specific regulation of HIV-1 gene expression by SERINC5 (now accepted for publication in mBio). From these findings, we propose to seek if SERINC5 affects the transcription profiles of the cells by directly or indirectly mediating the regulation of the interaction of transcription factors with promoters. We speculate a potential role for SERINC5 in altering the transcriptional status of a cell in a distinct manner depending on the stimuli. The primary objective of the proposal is to identify such instances of transcriptional regulation by SERINC5. The consequences of this regulation are expected to alter host pathways that affect downstream signaling. While we initially identified HIV-1 being the major pathogens that SERINC5 restricts, follow up studies pinpoint towards this cellular protein having effect on multitude of viruses such as MLV, EIAV, CSFV, Hepatitis, Influenza and SARS CoV-2. To understand a wholesome function for SERINC5 under physiologically relevant conditions, studying their role in infection of viruses and pathogens that are closely associated with HIV, would be pertinent. Herpes viruses such as HCMV, HHV-6 are commonly found co-infected with HIV-1. During one of our studies, we accidentally observed that SERINC5 affects the CMV promoter when provided exogenously (unpublished). These observations provide a supposition of SERINC5’s interaction with the Herpes viruses. For these objectives, we will utilize targeted cellular assays and develop methodologies/tools to study the functional significance of the signaling pathways SERINC5 triggers. Through these studies, we strive to deeply recognize all these roles that SERINC5 might confer which would pave the way to a new perspective to visualize host-virus interactions.