Analyses of Rotavirus NSP4 Genetic Groups, Structure, and Function
Judith M. Ball, Rebecca D. Parr and Clarence E. Schutt
from: Segmented Double-stranded RNA Viruses: Structure and Molecular Biology (Edited by: John T. Patton). Caister Academic Press, U.K. (2008)
NSP4 is a nonstructural, multi-functional glycoprotein with roles in RV morphogenesis, pathogenesis, and intracellular signaling events. Although traditionally classified as an integral ER glycoprotein, new data show NSP4 localizes to multiple intracellular sites outside of the ER. Novel NSP4-protein and -lipid interactions have been unveiled, which contribute to RV pathogenesis, and NSP4 structure and intracellular transport. Complimentary to these reports, several new functions have been disclosed, primarily through the use of silencing mRNA techniques. NSP4 contributes to viroplasm formation, distribution of viral proteins in infected cells, and regulation of viral transcription. As one of several virulence factors, NSP4 induces diarrhea by promoting a signaling event at the cell surface resulting in chloride secretion. NSP4 sequences are divided into distinct genetic groups that vary both in size and intracellular interactions. The crystal structure of NSP4 residues 95-137 discloses an extended, helical domain that folds as a coiled-coil and encompasses several binding sites. With the C-terminal structure in place, dissection of the many links between NSP4 structure-function and the complex interplay between NSP4 and host cell proteins are ongoing. This chapter summarizes NSP4 genetic variations and groupings, roles in rotavirus replication and pathogenesis, and the potential impact of NSP4 structure on function read more ...