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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Virology Study Section (VR)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Stanford University
Schools of Medicine
United States
Zip Code
Nair, Nitya; Feng, Ningguo; Blum, Lisa K et al. (2017) VP4- and VP7-specific antibodies mediate heterotypic immunity to rotavirus in humans. Sci Transl Med 9:
Li, Bin; Ding, Siyuan; Feng, Ningguo et al. (2017) Drebrin restricts rotavirus entry by inhibiting dynamin-mediated endocytosis. Proc Natl Acad Sci U S A 114:E3642-E3651
Sen, Adrish; Sharma, Ayushi; Greenberg, Harry B (2017) Rotavirus degrades multiple type interferon receptors to inhibit IFN signaling and protects against mortality from endotoxin in suckling mice. J Virol :
Zhu, Shu; Ding, Siyuan; Wang, Penghua et al. (2017) Nlrp9b inflammasome restricts rotavirus infection in intestinal epithelial cells. Nature 546:667-670
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
Sen, Adrish; Rott, Lusijah; Phan, Nguyen et al. (2014) Rotavirus NSP1 protein inhibits interferon-mediated STAT1 activation. J Virol 88:41-53
Uzri, Dina; Greenberg, Harry B (2013) Characterization of rotavirus RNAs that activate innate immune signaling through the RIG-I-like receptors. PLoS One 8:e69825
Deal, Emily M; Lahl, Katharina; Narváez, Carlos F et al. (2013) Plasmacytoid dendritic cells promote rotavirus-induced human and murine B cell responses. J Clin Invest 123:2464-74
Feng, Ningguo; Yasukawa, Linda L; Sen, Adrish et al. (2013) Permissive replication of homologous murine rotavirus in the mouse intestine is primarily regulated by VP4 and NSP1. J Virol 87:8307-16
Newell, Evan W; Sigal, Natalia; Nair, Nitya et al. (2013) Combinatorial tetramer staining and mass cytometry analysis facilitate T-cell epitope mapping and characterization. Nat Biotechnol 31:623-9

Showing the most recent 10 out of 41 publications