Abstract
Norovirus (NV) is a leading cause of gastroenteritis worldwide and a major public health concern. So far, the replication strategy of NV remains poorly understood, mainly because of the lack of a cell system to cultivate the virus. In this study, the function and the structure of a key viral enzyme of replication, the RNA-dependent RNA polymerase (RdRp, NS7), was examined. The overall structure of the NV NS7 RdRp was determined by X-ray crystallography to a 2.3 A (0.23 nm) resolution (PDB ID 2B43), displaying a right-hand fold typical of the template-dependent polynucleotide polymerases. Biochemical analysis evidenced that NV NS7 RdRp is active as a homodimer, with an apparent K(d) of 0.649 microM and a positive cooperativity (Hill coefficient n(H)=1.86). Crystals of the NV NS7 homodimer displayed lattices containing dimeric arrangements with high shape complementarity statistics. This experimental data on the structure and function of the NV RdRp may set the cornerstone for the development of polymerase inhibitors to control the infection with NV, a medically relevant pathogen.
Highlights
Norovirus (NV) is one of the major agents of viral gastroenteritis and a leading cause of food-borne gastroenteritis worldwide (Lopman et al, 2003, 2008)
Replication of the NV genome depends on viral enzymes of replication
The RNAdependent RNA polymerase (RdRp) is predicted to play an essential role being involved in the synthesis of antiviral genomic RNA, and subgenomic RNA
Summary
Norovirus (NV) is one of the major agents of viral gastroenteritis and a leading cause of food-borne gastroenteritis worldwide (Lopman et al, 2003, 2008). NV belongs to the family Caliciviridae, a virus family including human and non-human pathogenic strains. The genus Norovirus is divided into five genogroups. Strains belonging to genogroups 1, 2 and 4 infect humans, with the genogroup 2 strains being predominantly detected over the years. Animal NV strains, i.e. murine or bovine NV strains cluster mainly within genogroup 5 or 3, respectively (Zheng et al, 2006). The murine NV so far remains the only strain of the NV species that can be propagated in cultured cells
Sign-in/Register to view highlights & summary 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.
