Human rotaviruses are the leading cause of severe infantile diarrhea in the world. In the immunocompromised or elderly adult, rotaviruses are also an important cause of diarrheal disease. Rotavirus infection may also be associated with exacerbations of illness in patients with inflammatory bowel disease. In addition, rotaviruses can cause gastroenteritis in many other mammalian and avian species. In the decade since the discovery of human rotavirus much information has been gained concerning the nature of the viral genome (double stranded segmented RNA), the protein structure of the virus, the serologic and genetic relationship among rotaviral strains, and the epidemiology and pathophysiology of human rotavirus infection. Little information, however, has been generated concerning the genetic basis of viral virulence or host range. Furthermore, the protective role, in vivo, of antibody (IgG vs. IgA) to the two separate rotavirus surface proteins has not been examined. The genetic basis of virulence and the molecular determinants of host protection have obvious relevance to development of a successful strategy for the prevention of rotavirus diarrhea. The genetic basis of rotavirus virulence and host range will be determined by evaluating the pathogenicity of selected murine rotavirus X bovin rotavirus and murine rotavirus X simian rotavirus reassortants in a murine rotavirus infection model. As a second approach to determine the basis of viral virulence, alterations in viral pathogenicity will be examined in murine rotavirus variants selected with neutralizing monoclonal antibodies directed at either of the two viral surface proteins. Determinants of host protection will be studied with monoclonal antibodies (IgG and IgA) directed at the two surface proteins of murine rotavirus. Passive transfer of these monoclonal antibodies will be used to determine the rotavirus protein(s) and specific domains of the protein(s) that stimulate protective immunity. Comparison of the biologic effect of monoclonal antibodies with similar specificities but different isotypes (IgG vs. IgA) should help to clarify the role of local immunity in protection. The antigenic domains protective role of immunization with synthetic peptides.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Unknown (R22)
Project #
5R22AI021362-04
Application #
3444711
Study Section
Virology Study Section (VR)
Project Start
1984-07-01
Project End
1989-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
4
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Stanford University
Department
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
Nair, N; Newell, E W; Vollmers, C et al. (2016) High-dimensional immune profiling of total and rotavirus VP6-specific intestinal and circulating B cells by mass cytometry. Mucosal Immunol 9:68-82
Aoki, Scott T; Trask, Shane D; Coulson, Barbara S et al. (2011) Cross-linking of rotavirus outer capsid protein VP7 by antibodies or disulfides inhibits viral entry. J Virol 85:10509-17
Aoki, Scott T; Settembre, Ethan C; Trask, Shane D et al. (2009) Structure of rotavirus outer-layer protein VP7 bound with a neutralizing Fab. Science 324:1444-7
Warfield, Kelly L; Deal, Emily M; Bavari, Sina (2009) Filovirus infections. J Am Vet Med Assoc 234:1130-9
Jiang, Janina Q; He, Xiao-Song; Feng, Ningguo et al. (2008) Qualitative and quantitative characteristics of rotavirus-specific CD8 T cells vary depending on the route of infection. J Virol 82:6812-9
Arvin, Ann M; Greenberg, Harry B (2006) New viral vaccines. Virology 344:240-9
Feng, Ningguo; Jaimes, Maria C; Lazarus, Nicole H et al. (2006) Redundant role of chemokines CCL25/TECK and CCL28/MEC in IgA+ plasmablast recruitment to the intestinal lamina propria after rotavirus infection. J Immunol 176:5749-59
Blutt, Sarah E; Fenaux, Martijn; Warfield, Kelly L et al. (2006) Active viremia in rotavirus-infected mice. J Virol 80:6702-5
Glass, Roger I; Bhan, Maharaj K; Ray, Pratima et al. (2005) Development of candidate rotavirus vaccines derived from neonatal strains in India. J Infect Dis 192 Suppl 1:S30-5
Cuadras, Mariela A; Greenberg, Harry B (2003) Rotavirus infectious particles use lipid rafts during replication for transport to the cell surface in vitro and in vivo. Virology 313:308-21

Showing the most recent 10 out of 31 publications