Genetic Studies of Rotavirus Pathogenesis

Hoshino, Y.

Abstract

Continued efforts have been made to delineate the genetic mechanisms underlying virulence of rotavirus in the newborn gnotobiotic piglet model. A single gene substitution reassortant that had the 1st, 2nd, 5th, 6th, 7th, 8th, or 11th gene from human rotavirus DS-1 strain (which does not induce productive infection or diarrhea in gnotobiotic piglets) and the remaining ten genes from porcine rotavirus SB-1A strain (which consistently induces diarrhea in piglets) induced diarrhea in piglets that was associated with virus shedding. However, piglets challenged with a single gene substitution reassortant that had the VP3 gene, or VP4 gene, or VP7 gene, or NS-28 gene of DS-1 virus and the remaining ten genes from porcine SB-1A virus failed to develop illness or shed virus. Thus, we demonstrated that the 3rd, 4th, 9th (VP7), or 10th (NS28) gene each play an important role in virulence of rotavirus infection in piglets. Piglets challenged with a rotavirus reassortant that had the 3rd, 4th, 9th, and 10th genes of SB-1A virus and the remaining seven genes from DS-1 virus developed diarrhea and shed virus.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Intramural Research (Z01)
• Project #: 1Z01AI000340-11
• Application #: 3790729
• Support Year: 11
• Fiscal Year: 1992

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