SHREOSHRI BHATTACHARJEE, University of Saskatchewan

Shreoshri Bhattacharjee and Linda Chelico, College of Medicine, University of Saskatchewan, S7N 5E5

Fighting & Responding

The ongoing arms race between host defense mechanisms and viral evolution is central to understanding viral persistence and resistance. The Host restriction factors (HRFs) human APOBEC3, a family of cytidine deaminases are well established as antiviral molecules that work independent of cofactors yet having protein-protein interactions. We analyzed an existing APOBEC3 affinity purification and mass spectrometry (AP-MS) data set and determined that APOBEC3G (A3G) interacts with ZAP, a zinc-finger antiviral protein (also called ZCCHV). ZAP is a Pattern Recognition Receptor (PRR) that binds single stranded RNA and inhibits viral replication through targeting RNA for degradation and inhibiting its translation by binding to CpG dinucleotides. Both, A3G and ZAP are known to interact with HIV-1 RNA. ZAP action decreases HIV-1 titres and A3G induces mutations in newly formed HIV-1 (-) DNA. Despite these factors when expressed alone working at different HIV-1 lifecycle stages, we observed a combinatorial effect when co-expressed, resulting in enhanced reduction in HIV-1 infectious titres from producer cells when compared to ZAP alone. However, in a non infected cell, both the HRFs belong to DNA repair network to stabilize genome and respond to cellular stress. In some recent studies, ZAP and certain APOBEC3s have been observed to act as transcription factors for nucleosome/histone and Interferon stimulating response elements. Our study aims to understand the effect of ZAP and A3G together in regulating gene expression in a non infectious and HIV-1 infected cell, hence generating a broader perspective of HRFs total functionality.