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.
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.
| Strauss, Mike; Filman, David J; Belnap, David M et al. (2015) Nectin-like interactions between poliovirus and its receptor trigger conformational changes associated with cell entry. J Virol 89:4143-57 |
| Lin, Jun; Cheng, Naiqian; Hogle, James M et al. (2013) Conformational shift of a major poliovirus antigen confirmed by immuno-cryogenic electron microscopy. J Immunol 191:884-91 |
| Lin, Jun; Lee, Lily Y; Roivainen, Merja et al. (2012) Structure of the Fab-labeled ""breathing"" state of native poliovirus. J Virol 86:5959-62 |
| Lin, Jun; Cheng, Naiqian; Chow, Marie et al. (2011) An externalized polypeptide partitions between two distinct sites on genome-released poliovirus particles. J Virol 85:9974-83 |
