Dhairya Shah

Dhairya Shah

Mentor

Dr. Stephanie M. Karst

College

College of Medicine

Major

Microbiology and Cell Science

Minor

Health Disparities in Society

Organizations

American Physician Scientists Association, UF Chemistry Club

Academic Awards

N/A

Volunteering

Aces in Motion, NCF Regional Science Bowl Coordinator

Research Interests

Infectious Diseases, Virology, Molecular Genetics, and Microbiology

Hobbies and Interests

Chess, Tennis, KPop, and solving Rubik's cubes

Research Project

Determining the mechanism of the norovirus VP2 protein

Human noroviruses are the leading cause of severe childhood diarrhea and acute gastroenteritis outbreaks worldwide. Despite its high incidence of morbidity and widespread impact, there is limited knowledge about the pathogenic mechanisms underlying norovirus-induced disease. Human norovirus studies are limited by the difficulty of growing human norovirus in cell culture and lack of susceptible small animal models. Murine noroviruses (MNV) provide a tractable small animal model to investigate the pathogenic mechanisms and virulence of noroviruses in vivo. Recently, our lab has shown that genetically wild-type neonatal mice develop acute, self-resolving diarrhea following MNV-1 infection, a disease course that mirrors human norovirus pathogenesis. This is a novel and exciting discovery, especially since immunocompetent adult mice are asymptomatic and fail to develop overt disease when infected with MNV-1. Furthermore, genetically similar strains of MNV show differences in virulence as MNV-CR6 is attenuated compared to MNV-1. This difference in virulence allows us to determine which viral proteins (VP) are important in conferring virulence in vivo by producing chimeric viruses where genes encoding for individual viral proteins are swapped between the MNV-1 and MNV-CR6 strains. Our results have shown MNV-CR6 with the VP2 protein from MNV-1 has increased diarrhea incidence compared to the parental MNV-CR6. However, providing MNV-1 the MNV-CR6 VP2 protein, results in no significant change in diarrhea incidence, showing that VP2 is a sufficient but not necessary virulence factor. The neonatal mouse model will be used to determine which portion of the MNV-1 VP2 protein is important for its role as a virulence factor, with the following two aims: 

Specific Aim 1: Determine whether a predicted phosphorylation site is important for the virulence activity of the MNV-1 VP2 protein

Specific Aim 2: Determine whether a N-terminal transmembrane domain is important for the virulence activity of the MNV-1 VP2 protein