Temperature-dependent, Intermediate Particles from the Entry of Picornaviruses in

Brigham Young University, Provo UT

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Abstract

DESCRIPTION (provided by applicant): Non-enveloped viruses breach the formidable cell membrane and deposit their infectious nucleic acid in the appropriate cellular compartment, a process known as "cell entry." Mechanisms of entry for non-enveloped viruses are not well understood, though animal viruses are known to first interact with a cellular receptor. For poliovirus, the type member of the picornavirus family, the virus-receptor interaction induces temperature-dependent changes that allow entry. The picornaviruses are a group of significant human pathogens and are a model system for understanding entry of viruses into cells. We propose to investigate temperature-dependent transitions that occur during the cell entry of poliovirus. We propose to determine the three-dimensional structures of intermediate particles via cryogenic electron microscopy. After 3D structures are determined, we will model the transitions by fitting atomic-resolution coordinates into the cryo-EM structures. Our work should give insights into the mechanisms of cell entry for picornaviruses and other non-enveloped viruses. The project will include two concurrent undergraduate students as primary researchers throughout the duration of the project. PUBLIC HEALTH RELEVANCE: Viruses must enter cells to affect living things. Picornaviruses (e.g. common-cold viruses, poliovirus, and hepatitis A virus) are important human pathogens. Understanding the entry process of picornaviruses will give a fuller mechanistic picture of how these and other viruses cause disease and may give insights into anti-viral therapies.