Submitted to: Journal of Virology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 2/6/2004
Publication Date: 6/1/2004
Citation: Chen, R., Neill, J.D., Noel, J.S., Huston, A.M., Glass, R.I., Estes, M.K., Prasad, B.V. 2004. Inter and intragenus structural variations in caliciviruses and their functional implications. Journal of Virology. 78(12):6469-6479. Interpretive Summary: Emerging or newly discovered viruses are becoming more of a threat to both human and animal health. Some of these viruses belong to the calicivirus family of viruses. The enteric caliciviruses, a group that includes viruses that infect man, cattle and swine, do not grow in cell cultures. The human enteric caliciviruses are a major cause of viral food poisoning, while the swine and cattle caliciviruses may be involved in diarrhea outbreaks in livestock herds. Because these viruses cannot be grown in the laboratory, they are difficult to study. To better understand the infection process, San Miguel sea lion viruses, caliciviruses that grow well in the laboratory, were studied. They are similar to the enteric caliciviruses and can be used as a model for studying mechanisms of virus replication and pathology. This study describes further work determining the structure of the virus particle. This work has shown that the San Miguel sea lion virus is similar to the human enteric caliciviruses. Further research efforts will now be directed toward understanding the virus particle in even greater detail. This information will allow researchers to understand the infection process of the caliciviruses and may lead to the design of better vaccines to combat viral infections.
Technical Abstract: The family Caliciviridae is divided into four genera and consists of single-stranded RNA viruses with hosts ranging from humans to a wide variety of animals. Human caliciviruses are the major cause of outbreaks of acute nonbacterial gastroenteritis, whereas animal caliciviruses cause various host-dependent illnesses with a documented potential for zoonoses. To investigate inter- and intragenus structural variations and to provide a better understanding of the structural basis of host specificity and strain diversity, we performed structural studies of the recombinant capsid of Grimsby virus, the recombinant capsid of Parkville virus, and San Miguel sea lion virus serotype 4 (SMSV4), which are representative of the genera Norovirus (genogroup 2), Sapovirus, and Vesivirus, respectively. A comparative analysis of these structures was performed with that of the recombinant capsid of Norwalk virus, a prototype member of Norovirus genogroup 1. Although these capsids share a common architectural framework of 90 dimers of the capsid protein arranged on a T=3 icosahedral lattice with a modular domain organization of the subunit consisting of a shell (S) domain and a protrusion (P) domain, they exhibit distinct differences. The distally located P2 subdomain of P shows the most prominent differences both in shape and in size, in accordance with the observed sequence variability. Another major difference is in the relative orientation between the S and P domains, particularly between those of noroviruses and other caliciviruses. Despite being a human pathogen, the Parkville virus capsid shows more structural similarity to SMSV4, an animal calicivirus, suggesting a closer relationship between sapoviruses and animal caliciviruses. These comparative structural studies of caliciviruses provide a functional rationale for the unique modular domain organization of the capsid protein with an embedded flexibility reminiscent of an antibody structure. The highly conserved S domain functions to provide an icosahedral scaffold; the hypervariable P2 subdomain may function as a replaceable module to confer host specificity and strain diversity; and the P1 subdomain, located between S and P2, provides additional fine-tuning to position the P2 subdomain.