How Does Protein Structure Control Viral Infection?

When animals are infected by a virus, a battleground is created that consists of interactions between the proteins of the virus and those of the host. Virulence and disease occurs when viral proteins interact with host cell receptors to allow binding, uptake, intracellular trafficking and infection. Interactions of the virus with host antibodies, on the other hand, may neutralize infection. Despite their importance, many of the functions of viral structural proteins are still not well understood, including how the receptor- or antibody-binding controls infection.

Colin R. Parrish, Baker Institute for Animal Health, is continuing to investigate these processes, using the protein shells, called capsids, of parvovirus, a class of viruses that infects humans and animals. They are collaborating closely with the lab of Susan Hafenstein (Pennsylvania State University), an expert in the analysis of protein structures. The team is using animal parvoviruses as models, including canine parvovirus, which arose as a new pandemic pathogen due to changes in its interaction with a specific type of host receptor. The capsids also bind to the immune system’s antibodies, with significant variation in how the different antibodies neutralize the viral infection. Parrish’s group has already generated important new information about the interactions between capsids, receptors, and antibodies, and the tools developed now allow them to manipulate each component to understand how it controls virus infection.

They are working to explain the structural role of the host receptor in controlling the infection of cells, and in understanding the effects of receptor variation in different animals. The work will explain how altered receptor binding can lead to the emergence of new epidemic viruses. In other studies that are defining the interactions of antibodies with the capsid, they seek to explain the mechanisms of binding and neutralization, revealing new ways to make more effective vaccines or therapeutics. NIH Award Number: 2R01AI092571-06A1

Cornell Researchers

Funding Received

$1.9 Million spanning 5 years