Tomohiro Kotaki, Osaka University

Tomohiro Kotaki1, Yuta Kanai1, Kristen M. Ogden2, Megumi Onishi1, Kattareeya Kumthip3,4, Pattara Khamrin3,4, Patcharaporn Boonyos5, Pornkamol Phoosangwalthong5, Phakapun Singchai6, Tipsuda Luechakham6, Shohei Minami1, Zelin Chen1, Katsuhisa Hirai1, Ratana Tacharoenmuang6, Hiroto Mizushima5, Hiroshi Ushijima7, Niwat Maneekarn 3,4, Takeshi Kobayashi1,8,9* 1Department of Virology, Research Institute for Microbial Diseases, Osaka University, Japan. 2Department of Pediatrics, Vanderbilt University Medical Center, United States. 3Department of Microbiology, Faculty of Medicine, Chiang Mai University, Thailand. 4Center of Excellence in Emerging and Re-emerging Diarrheal Viruses, Chiang Mai University, Thailand. 5Thailand-Japan Research Collaboration Center on Emerging and Re-emerging Infections, Research Institute for Microbial Diseases, Osaka University, Japan. 6Department of Medical Sciences, Ministry of Public Health, Thailand. 7Department of Pathology and Microbiology, Nihon University School of Medicine, Japan. 8Center for Infectious Disease Education and Research, Osaka University, Japan. 9Center for Advanced Modalities and DDS, Osaka University, Japan.

Epidemiology, Evolution, and Diversity

Rotavirus infections remain a significant cause of morbidity and mortality in infants. The viral surface proteins VP4 and VP7 are each classified into multiple genotypes (P[1]–P[58] for VP4 and G1–G42 for VP7), which differ in their susceptibility to neutralizing antibodies. However, detailed analyses of these differences remain limited. This study investigates the susceptibility of diverse VP4 and VP7 genotypes to neutralizing antibodies induced by vaccination or natural infection. A reverse genetics system based on the human rotavirus Odelia strain (G4P[8]) was used to create monoreassortant viruses by replacing the VP4 or VP7 genes with those from clinical isolates (obtained in Thailand) or prototype strains. We generated 11 VP4 and 19 VP7 reassortants, covering seven and 17 genotypes, respectively. Neutralization tests using the monoreassortant viruses, immune sera, and MA104 cells indicate that the VP7 genotype, rather than the VP4 genotype, primarily influences susceptibility to neutralization. Furthermore, genotypes G2, bat-like G3, G11, G12, G25, and G33 were significantly less susceptible to sera from naturally infected Thai individuals, highlighting the importance of monitoring these genotypes. To identify the protein region responsible for susceptibility to neutralization, we generated chimeric viruses by exchanging the domains of high- and low-susceptibility VP7 genotypes and found that Domain I is a key determinant of susceptibility. Thus, we identified multiple rotavirus genotypes with reduced susceptibility to neutralization, as well as the region primarily responsible for this reduction. These findings may help to predict possible future rotavirus outbreaks in humans and facilitate development of effective rotavirus vaccines.