Viperin is a conserved ER membrane-associated protein encoded by an interferon-stimulated gene and has demonstrated antiviral activity. While viperin’s antiviral activity can be attributed to its radical SAM-dependent synthesis of the chain-terminating nucleotide ddhCTP, which interferes with viral replication, it has also been shown to interact with various cellular pathways implicated in viral infection. Furthermore, viperin interacts with viral proteins that localize to the endoplasmic reticulum, such as NS3, in Tick-Borne Encephalitis and Zika virus infections, and NS5A in Hepatitis C virus infections. Experiments using proteasomal inhibitors suggest that viperin stimulates the proteasomal degradation of both viral proteins, though the exact mechanism is unknown. Viperin has not been shown to possess a ubiquitin binding domain and is thought to interact with an E3 ubiquitin ligase while complexed with viral protein. Furthermore, replicating these interactions <i>in vitro </i>using constructs lacking the membrane-binding domain has proved challenging. Viperin has recently been incorporated into nano discs by our group, and we present recent progress aimed towards optimizing and characterizing this system. This research will facilitate <i>in vitro</i> studies of the enzyme interacting with other ER-membrane associated proteins by providing a native-mimetic environment. Specifically, the development of a nano disc system incorporating viperin will allow us to characterize complex formation of viperin and viral proteins. Furthermore, this system will be applied to probe the interactions of E3 ligases that, mediated by viperin, lead to the proteasomal degradation of viral protein. This will further help establish an additional mode of action for viperin’s antiviral activity. Ultimately, understanding how viperin may act as an agonist of proteasomal degradation would elucidate its roles both in antiviral defense and cellular metabolic regulation.

Exploring viperin’s role in the degradation of viral proteins using a membrane mimetic system

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.