Rapid progress in understanding the epidemiology and molecular virology of human caliciviruses (HuCVs) in the past decade has highlighted the importance of HuCVs as a cause of acute gastroenteritis. The recent finding that Noroviruses (NVs) recognize human histo-blood group antigens (HBGAs) as receptors has provided new approaches to develop strategies to control and prevent NV gastroenteritis. The increasing epidemics and emergence of new epidemic variants of the globally dominant GII-4 viruses in many countries indicate that studies to increase our understanding of the role of genetic and host factors in the epidemiology and evolution of NVs are necessary. This renewal builds on the scientific productivity of the past and will seek new information to build new platforms for future development and evaluation of intervention/prevention strategies against HuCVs. 1) We will perform cryo-EM and site-directed mutagenesis analyses with NV P particles as a model to characterize the receptor binding interface and the carbohydrate interaction sites in association with the antibody-based blocking (""""""""neutralization"""""""") of NV binding to HBGA receptors. 2) We will perform genetic and phenotypic analyses using our large collection of clinical samples to seek evidence of host factors in the evolution of NVs and to address a currently urgent important question on the epidemics or pandemics of the globally dominant GII-4 type of NVs in many countries. And finally, 3) we will take advantage of the novel rhesus enteric CV, the Tulane virus, as a model to further elucidate the virus/host interaction related to the host HBGA receptors to NVs and to use the newly developed reverse genetics system of TV to address questions related to host/pathogen interaction in attempt to developing research tools and vaccines against NVs.
This application will utilize molecular epidemiology and molecular virology approaches to study the host range, virus-receptor interaction, strain variation, classification and evolution of NVs, which may lead to new strategies in diagnosis and disease control and prevention of NV associated gastroenteritis. It will also study a newly discovered rhesus enteric CV which will be invaluable in study of the implications of receptor ligand binding and antibody protection which could also result in research tools and a model system for evaluation treatment and prevention strategies.
| Dai, Ying-Chun; Zhang, Xu-Fu; Xia, Ming et al. (2015) Antigenic Relatedness of Norovirus GII.4 Variants Determined by Human Challenge Sera. PLoS One 10:e0124945 |
| Jin, Miao; Tan, Ming; Xia, Ming et al. (2015) Strain-specific interaction of a GII.10 Norovirus with HBGAs. Virology 476:386-94 |
| Tan, Ming; Jiang, Xi (2014) Histo-blood group antigens: a common niche for norovirus and rotavirus. Expert Rev Mol Med 16:e5 |
| Wei, Chao; Meller, Jarek; Jiang, Xi (2013) Substrate specificity of Tulane virus protease. Virology 436:24-32 |
| Fan, Qiang; Wei, Chao; Xia, Ming et al. (2013) Inhibition of Tulane virus replication in vitro with RNA interference. J Med Virol 85:179-86 |
| Dai, Ying-Chun; Zhang, Xu-Fu; Tan, Ming et al. (2013) A dual chicken IgY against rotavirus and norovirus. Antiviral Res 97:293-300 |
| Fang, Hao; Tan, Ming; Xia, Ming et al. (2013) Norovirus P particle efficiently elicits innate, humoral and cellular immunity. PLoS One 8:e63269 |
| Liu, Yang; Huang, Pengwei; Jiang, Baoming et al. (2013) Poly-LacNAc as an age-specific ligand for rotavirus P[11] in neonates and infants. PLoS One 8:e78113 |
| Yu, Guimei; Zhang, Dongsheng; Guo, Fei et al. (2013) Cryo-EM structure of a novel calicivirus, Tulane virus. PLoS One 8:e59817 |
| Liu, Yang; Huang, Pengwei; Tan, Ming et al. (2012) Rotavirus VP8*: phylogeny, host range, and interaction with histo-blood group antigens. J Virol 86:9899-910 |
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