Noroviruses are a collection of genetically diverse, non-enveloped members of the Caliciviridae family, possessing a positive sense, single-stranded RNA (+ssRNA) genome that typically encodes 7 non-structural (NS) proteins and two structural proteins (VP1-2). Our lab has previously been shown that Norovirus infection leads to selective repression of host translation, mediated by the NS protein NS3. This activity is linked to the suppression of the immune response, and induction of apoptosis however, its mechanism is yet to be elucidated and the role of NS3 in Norovirus pathogenesis is incompletely understood. With the importance of translational downregulation becoming increasingly apparent, our preliminary proteomic data has highlighted a potential interaction between NS3 and a cellular translation factor poly-A interacting protein 1 (PAIP1). Herein we describe a role for PAIP1 in norovirus infection, and connect this to an interaction with NS3. We show that PAIP1 is recruited to the replication complex upon infection, and through transient expression studies demonstrate a potential interaction between PAIP1 and NS3. Using truncated NS3 constructs we identify the domain within NS3 responsible for this interaction, and through alanine scanning mutations, reveal the specific amino acids involved. We aim to show that this interaction is then functionally linked to NS3 mediated translational repression, and the key downstream processes such as immune evasion, induction of apoptosis and virus egress. Moreover, we aim to demonstrate the importance of NS3 and PAIP1 to viral replication and describe the functional implications of specific mutations within NS3. This study will contribute greatly to our understanding of how viruses interact with, and manipulate their hosts; and identify novel targets for much needed vaccines and therapeutics.