Abstract
Murine norovirus (MNV) viral protein genome-linked (VPg) manipulates the cell cycle to induce a G0/G1 arrest and gain a beneficial replication environment. All viruses of the norovirus genus encode a VPg protein; however, it is unknown if the G0/G1 arrest induced by MNV VPg is conserved in other members of the genus. RNA transcripts encoding a representative viral VPg from five norovirus genogroups were transfected into RAW-Blue murine macrophages, and the percentage of cells in each phase of the cell cycle was determined. A G0/G1 cell cycle arrest was observed for all norovirus VPg proteins tested, and in the wider Caliciviridae family the arrest was also conserved in rabbit hemorrhagic disease virus (RHDV) VPg and human sapovirus (HuSV) VPg. Truncation of MNV VPg shows that the first 62 amino acids are sufficient for a cell cycle arrest, and alignment of VPg sequences revealed a conserved motif in the N-terminal region of VPg. Analysis of VPg constructs with single N-terminal region point mutations, or exchange of N-terminal regions between VPg proteins, confirmed the importance of the N-terminal region for cell cycle arrest. These results provide evidence that G0/G1 cell cycle arrest is a conserved function of norovirus VPg proteins that involves the N-terminal region of these proteins.
Highlights
Noroviruses are a genus of the Caliciviridae family, which includes the Nebovirus, Lagovirus, Vesivirus and Sapovirus genera [1]
All viruses of the Caliciviridae family encode a viral protein genome-linked (VPg) protein, but it is unknown if the cell cycle manipulation shown for murine norovirus (MNV) VPg is conserved
MNV VPg, but mutation of G9 did not significantly affect the cell cycle (Figure 5C). These results indicate that lysine and arginine residues within the N-terminal region of MNV VPg are important for a cell cycle arrest
Summary
Noroviruses are a genus of the Caliciviridae family, which includes the Nebovirus, Lagovirus, Vesivirus and Sapovirus genera [1]. The norovirus genus is further divided into at least five genogroups (GI–V), infecting a diverse range of host organisms [1,2]. Human noroviruses (HuNV) are a major cause of viral gastroenteritis, affecting people of all age groups [3]. Despite advances in the development of in vitro cell culture systems for HuNV, including B cells and stem cell-derived human enteroids, direct study of the virus remains challenging [7,8,9,10]. Murine norovirus (MNV) is often used as a model virus, as it retains a similar genetic layout to HuNV and exhibits robust replication in cell culture systems [11,12,13]. The norovirus genome is organized into three open reading frames (ORF). ORF1 encodes a large polyprotein, which is subsequently cleaved by the viral protease into the non-structural proteins NS1-2, NS3, NS4, NS5
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
