Life Sciences Seminar: Trafficking of viral ribonucleoproteins in the cytoplasm of host cells
Life Sciences Seminar
Trafficking of viral ribonucleoproteins in the cytoplasm of host cells
Dr. Douglas Lyles
Professor, Department of Biochemistry
Wake Forest School of Medicine
The ribonucleoprotein (RNP) cores, or nucleocapsids, of negative-strand RNA viruses are too large to freely diffuse through the cytoplasm of eukaryotic cells due to the dense network of actin filaments and other cytoskeletal elements. Nonetheless, they migrate extensively at early times post-infection to form inclusion bodies for viral RNA synthesis. At later times they also migrate out of inclusion bodies to form additional inclusion bodies, and they migrate to the plasma membrane for virus assembly. Most of the research on this problem has focused on directed motion driven by molecular motors along cytoskeletal elements such as microtubules and actin filaments. However, live-cell imaging data shows that relatively few viral RNPs undergo directed motion. Instead, the motion of the majority consists of short movements in random directions that resemble thermally-driven diffusion, i.e., Brownian motion. We have shown that vesicular stomatitis virus (VSV) RNPs move through the cytoplasm primarily by rapidly bouncing back and forth within traps and hopping from trap to trap in random directions. Key elements of the approach were rapid data acquisition and a recently developed analysis using pattern recognition methods. These approaches showed that traps are formed, in part, by cytoskeletal elements like actin filaments, that actin filaments also play a role in hopping-like motion due to myosin II motors, and that these motions are the key aspects of a cellular process referred to as “active diffusion.”
Dr. Lyles received his bachelor’s degree in biochemistry at the University of Pennsylvania and his Ph.D. in biochemistry from the University of Mississippi Medical Center. He did his postdoctoral training in virology at the Rockefeller University. Dr. Lyles joined the faculty of Wake Forest School of Medicine in 1978 in the Department of Microbiology and Immunology. He served as Chair of Biochemistry and Leader of the Tumor Progression and Recurrence Program of the Comprehensive Cancer Center of Wake Forest University from 2004-2018. Dr. Lyles was trained as a membrane biophysicist and has been engaged in research on the structure and assembly of virus envelopes throughout his career. Most of this research has focused on vesicular stomatitis virus (VSV), which is widely used in the study of virus envelope assembly, virus-host interaction, and as a model for cellular biology. He also has a long-standing research program on the suppression of host gene expression by the matrix protein of VSV. This is the major mechanism by which the virus suppresses host antiviral responses. His interest in antiviral signaling has led the development of novel oncolytic viruses and provided new insights into the relationship between oncogenesis and antiviral signaling.
Beginners, undergraduates, graduates. Those with interest in the topic.
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