Previously, in studies involving a semi-homologous system of gnotobiotic newborn pigs and a virulent porcine rotavirus strain (SB-1A) and an avirulent human rotavirus strain (DS-1) and their reassortants, we demonstrated that: (i) the third (VP3), fourth (VP4), ninth (VP7), or tenth (NSP4) porcine rotavirus gene each play an important independent role in the virulence of rotavirus infection in piglets; and (ii) all four of the porcine rotavirus virulence-associated genes are required for the induction of diarrhea and the shedding of rotavirus by piglets. These observations suggested a potential new strategy for attenuation of wild-type human rotaviruses of major epidemiological importance and its application to the development of a safe and effective vaccine. Using this strategy, we were successful in generating four double gene substitution human x bovine rotavirus reassortants, each of which processed the following: (i) the VP4-encoding gene from human rotavirus Wa (VP4:1A); (ii) the VP7-encoding gene from human rotavirus D (VP7:1), DS-1 (VP7:2), P (VP7:3) or ST3 (VP7:4); and (iii) the remaining nine genes including the VP3-encoding gene and NSP4-encoding gene from bovine rotavirus UK. In addition, we successfully generated two human x bovine and two human x rhesus rotavirus single gene substitution reassortants, each of which had the VP4- encoding gene from human rotavirus Wa (VP4:1A) or DS-1 (VP4:1B) and the remaining genes from either bovine rotavirus UK or rhesus rotavirus MMU18006. Recently, unusual VP7 (G) serotypes causing a high incidence of human infection have been detected in various parts of the world including G5 strains in Brazil, and G9 and G10 strains in India. Because of the possibility in the future that such G serotypes might need to be included in our vaccine candidates and therefore to ?be prepared?, we generated three rhesus x human and three bovine x human rotavirus reassortants, each of which had only one gene from human rotavirus encoding G5, G9, or G10 specificity, and the remaining genes from either rhesus rotavirus MMU18006 or bovine rotavirus UK. Such strains may prove to be important for the development of an optimally effective rotavirus vaccine.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000340-17
Application #
6098913
Study Section
Special Emphasis Panel (LID)
Project Start
Project End
Budget Start
Budget End
Support Year
17
Fiscal Year
1998
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Feng, N; Sen, A; Nguyen, H et al. (2009) Variation in antagonism of the interferon response to rotavirus NSP1 results in differential infectivity in mouse embryonic fibroblasts. J Virol 83:6987-94
Ross, Jerri; Ostlund, Eileen N; Cao, Dianjun et al. (2008) Acrylamide concentration affects the relative position of VP7 gene of serotype G2 strains as determined by polyacrylamide gel electrophoresis. J Clin Virol 42:374-80
Kapikian, Albert Z; Hoshino, Yasutaka (2007) To serotype or not to serotype: that is still the question. J Infect Dis 195:611-4
Vesikari, Timo; Karvonen, Aino V; Majuri, Jukka et al. (2006) Safety, Efficacy, and Immunogenicity of 2 Doses of Bovine-Human (UK) and Rhesus-Rhesus-Human Rotavirus Reassortant Tetravalent Vaccines in Finnish Children. J Infect Dis 194:370-6
Vesikari, Timo; Karvonen, Aino; Forrest, Bruce D et al. (2006) Neonatal administration of rhesus rotavirus tetravalent vaccine. Pediatr Infect Dis J 25:118-22
Hoshino, Yasutaka; Honma, Shinjiro; Jones, Ronald W et al. (2005) A porcine G9 rotavirus strain shares neutralization and VP7 phylogenetic sequence lineage 3 characteristics with contemporary human G9 rotavirus strains. Virology 332:177-88
Hoshino, Yasutaka; Jones, Ronald W; Ross, Jerri et al. (2005) Porcine rotavirus strain Gottfried-based human rotavirus candidate vaccines: construction and characterization. Vaccine 23:3791-9
Kapikian, Albert Z; Simonsen, Lone; Vesikari, Timo et al. (2005) A hexavalent human rotavirus-bovine rotavirus (UK) reassortant vaccine designed for use in developing countries and delivered in a schedule with the potential to eliminate the risk of intussusception. J Infect Dis 192 Suppl 1:S22-9
Yuan, Lijuan; Ishida, Shin-Ichi; Honma, Shinjiro et al. (2004) Homotypic and heterotypic serum isotype-specific antibody responses to rotavirus nonstructural protein 4 and viral protein (VP) 4, VP6, and VP7 in infants who received selected live oral rotavirus vaccines. J Infect Dis 189:1833-45
Hoshino, Yasutaka; Jones, Ronald W; Ross, Jerri et al. (2004) Rotavirus serotype G9 strains belonging to VP7 gene phylogenetic sequence lineage 1 may be more suitable for serotype G9 vaccine candidates than those belonging to lineage 2 or 3. J Virol 78:7795-802

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