Genetic Studies of Rotavirus Pathogenesis

Hoshino, Y.

Abstract

Previously, by using a semi-homologous system of gnotobiotic newborn pigs and virulent porcine rotavirus (strain SB-1A) and avirulent human rotavirus (strain DS-1) and their reassortants, we demonstrated that: (i) the 3rd (VP3), 4th (VP4), 9th (VP7), or 10th (NS28) porcine rotavirus gene each play an important independent role in 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 virus by piglets. These observations suggested a new potential strategy for attenuation of wild-type human rotaviruses of major epidemiologic importance and the subsequent development of a safe and effective vaccine. Based on this strategy efforts were made to generate four human x bovine rotavirus reassortants, each of which has: (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 9 genes including the VP3-encoding gene and NS28-encoding gene from bovine rotavirus UK. In addition, we successfully generated two human x bovine rotavirus reassortants, each of which had the VP4- encoding gene from human rotavirus Wa (VP4:1A) or DS-1 (VP4:1B) and the remaining 10 genes from bovine rotavirus UK.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Intramural Research (Z01)
• Project #: 1Z01AI000340-13
• Application #: 3746513
• Support Year: 13
• Fiscal Year: 1994

Institution

• Name: National Institute of Allergy and Infectious Diseases
• Country: United States

Publications

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