Structural Controls of Functional Receptor and Antibody Binding to Viral Capsids

Principal Investigator: Colin Parrish

Baker Institute for Animal Health
Sponsor: NIH-National Institute of Allergy and Infectious Diseases (NIAID)
Grant Number: 3R01AI092571-08S1
Title: Structural Controls of Functional Receptor and Antibody Binding to Viral Capsids
Project Amount: $47,830
Project Period: August 2019 to April 2020

DESCRIPTION (provided by applicant): 

Cell infection by animal viruses is controlled by their structural proteins and by variation in those structures. Viral proteins interact with host cell receptors, leading to binding, uptake and intracellular trafficking, while interactions with host antibodies may neutralize infection with varying efficiencies. Many functions of viral structural proteins are still not fully understood, including the structural effects of receptor or antibody binding in controlling infection. Here we will continue to investigate those processes using parvovirus capsids as a model. The viruses being studied include canine parvovirus (CPV), which arose as a new pandemic pathogen due to changes in its interaction with the host transferrin receptor type-1 (TfR). The parvovirus capsids also bind antibodies to several epitopes with significant variation in the resulting neutralization. In the previous period, we have generated important new information about the structures and functions of capsids, the roles of TfR variants in infection, and the binding of antibodies. The tools developed allow us to manipulate each component in order to understand how they control virus infection.