CHS Research Group Noroviruses
Dr. Grant Hansman
The Caliciviridae family comprises of at least five genera (norovirus, sapovirus, lagovirus, vesivirus, and nebovirus) and these viruses cause a variety of diseases in both humans and animals. Human noroviruses are the best studied among the caliciviruses and are the dominant cause of outbreaks of gastroenteritis around the world. Based on the capsid gene sequence, noroviruses are divided into 6 main genogroups (GI to GVI) and over 30 genotypes. All known noroviruses are species specific, only GI, GII, and GIV cause gastroenteritis in humans, whereas GIII, GV, and GVI cause disease in animals. While some animal caliciviruses can be cultivated, human noroviruses cannot be grown in tissue culture and only limited number of laboratory animal models are available. Caliciviruses are non-enveloped positive sense RNA viruses with a single capsid protein that can be divided into a shell (S) and protruding (P) domain. The P domain is highly variable, but likely contains determinates for cell attachment and entry.
My research group is mainly focusing on the norovirus capsid using structural biology (X-ray crystallography and cryo-EM). We are interested in the structural basis for norovirus capsid binding to a known host factor (histo-blood group antigens - HBGAs), deciphering norovirus capsid flexibility (nanobodies and monoclonal antibodies), and discovering and developing norovirus antivirals against the capsid (fucose compounds, NIH clinical collection, and drug design).
Hansman GS, Taylor DW, McLellan JS, Smith TJ, Georgiev I, Tame JRH, Park SY, Yamazaki M, Gondaira F, Miki M, Katayama K, Murata K, and Kwong PD. (2012) Structural basis for broad detection of genogroup II noroviruses by a monoclonal antibody that binds to a site occluded in the viral particle. J Virol 86: 3635-3646.
Hansman GS, Shahzad-ul-Hussan S, McLellan JS, Chuang G, Georgiev I, Shimoike, T, Katayama K, Bewley, CA, and Kwong PD. (2012) Structural basis for norovirus inhibition and fucose mimicry by citrate. J Virol 86: 284-292.
Hansman GS, Biertümpfel C, Georgiev I, McLellan JS, Chen L, Zhou T, Katayama K, Kwong PD. (2011) Crystal Structures of GII.10 and GII.12 Norovirus Protruding Domains in Complex with Histo-Blood Group Antigens Reveal Details for a Potential Site of Vulnerability. J Virol 85: 6687-6701.
Ozawa K, Oka T, Takeda N Hansman GS (2007) Norovirus infections in symptomatic and asymptomatic food handlers in Japan. J Clin Microbiol 45: 3996-4005