Noroviruses in the Caliciviridae are a major cause of acute gastroenteritis in all age groups. The illness occurs often in settings where people are in close contact, such as families, nursing homes, hospitals, schools, camps, cruise ships, military barracks, and social gatherings. In most individuals, norovirus gastroenteritis (known commonly as “stomach flu”) resolves in two to three days. However, in patients with underlying conditions such as immunosuppression or in the very old and young, the illness can become life-threatening. There are presently no approved vaccines or specific antiviral drugs for the noroviruses, and the overall goal of this research program is to advance their development.
One of the major specific areas of research in our laboratory is to develop experimental systems in which to study norovirus replication and immunity. The inability to grow the human noroviruses associated with acute gastroenteritis has been a major research obstacle. We have conducted comparative studies among diverse members of the Caliciviridae in an effort to learn common themes in calicivirus replication that will inform our understanding of the human noroviruses. Recent breakthroughs include the first visualization of calicivirus replication in real time by the introduction of a fluorescent protein marker in the feline calicivirus genome, a proof of concept study for human norovirus vaccines in an animal model, and the mapping of functional epitopes in a predominant norovirus genotype.
Computer-generated image of Gii.4 norovirus capsid protein, showing 1974 strain superimposed over modern strain.Credit: NIAID
The predominant norovirus strain associated with gastroenteritis outbreaks is named GII.4. Because the prototype norovirus strain, Norwalk virus, was discovered at NIAID by Dr. Albert Kapikian in 1972, NIAID has an extensive collection of archival specimens. We have studied how the surface of the GII.4 virion has changed over the decades to gain insight into how norovirus vaccines should be designed. In this computer-generated image of the GII.4 norovirus capsid protein, a model of the GII.4 virus in 1974 (orange) is superimposed over a more recent GII.4 strain (pink). The blue sticks represent a histo-blood group carbohydrate molecule that many noroviruses recognize on intestinal cells. This binding site has changed little in GII.4 noroviruses for over three decades. However, other regions show minor differences that might influence antibody recognition.
Dr. Green earned her Ph.D. from the University of Tennessee Center for Health Sciences in Memphis in the department of microbiology and immunology. She joined the Laboratory of Infectious Diseases in 1986 and has focused on the study of viruses associated with gastroenteritis. In recent years, her research program has addressed the role of noroviruses in human disease, with an emphasis on the development of prevention and control strategies.
Stanislav V. Sosnovtsev, Karin Bok, Gabriel I. Parra, Carlos Sandoval-Jaime, Eugenio J. Abente, and Rachel J. Dexter
Parra GI, Abente EJ, Sandoval-Jaime C, Sosnovtsev SV, Bok K, Green KY. Multiple antigenic sites are involved in blocking the interaction of GII.4 norovirus capsid with ABH histo-blood group antigens. J Virol. 2012 Apr 24. Epub ahead of print.
Parra GI, Bok K, Taylor R, Haynes JR, Sosnovtsev SV, Richardson C, Green KY. Immunogenicity and specificity of norovirus Consensus GII.4 virus-like particles in monovalent and bivalent vaccine formulations. Vaccine. 2012 May 21;30(24):3580-6.
Barron EL, Sosnovtsev SV, Bok K, Prikhodko V, Sandoval-Jaime C, Rhodes CR, Hasenkrug K, Carmody AB, Ward JM, Perdue K, Green KY. Diversity of murine norovirus strains isolated from asymptomatic mice of different genetic backgrounds within a single U.S. research institute. PLoS One. 2011;6(6):e21435.
Bok K, Parra GI, Mitra T, Abente E, Shaver CK, Boon D, Engle R, Yu C, Kapikian AZ, Sosnovtsev SV, Purcell RH, Green KY. Chimpanzees as an animal model for human norovirus infection and vaccine development. Proc Natl Acad Sci U S A. 2011 Jan 4;108(1):325-30.
Abente EJ, Sosnovtsev SV, Bok K, Green KY. Visualization of feline calicivirus replication in real-time with recombinant viruses engineered to express fluorescent reporter proteins. Virology. 2010 Apr 25;400(1):18-31.
Bok K, Abente EJ, Realpe-Quintero M, Mitra T, Sosnovtsev SV, Kapikian AZ, Green KY. Evolutionary dynamics of GII.4 noroviruses over a 34-year period. J Virol. 2009 Nov;83(22):11890-901.
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Last Updated September 20, 2012