Dynamics of key viral attack strategy visible for first time

phys.org | June 06, 2019

Many infectious viruses, from HIV to West Nile, rely on a fundamental biological process called frameshifting to maximize their attack. Long identified as a key mechanism that viruses use to proliferate inside their hosts, the real-time dynamics of frameshifting had never been directly observed, until now. For the first time, Colorado State University scientists Tim Stasevich and Brian Munsky have developed detailed imaging technology and computational analyses to visualize, quantify and understand frameshifting mechanisms at the level of single molecules in living cells. The publication of their work June 6 in the journal Molecular Cellincludes first author and graduate student Kenneth Lyon, and computational modeling support from postdoctoral researcher Luis Aguilera. "Our hope is that these integrated experimental and computational methods, allowing us to observe and predict unique aspects of viral replication, can offer strategies for future antiviral therapies," said Stasevich, a Monfort Professor and assistant professor in the Department of Biochemistry and Molecular Biology. HIV is one example of a retrovirus, meaning it carries genetic information in a molecule called RNA, rather than DNA. When a virus infects a host cell, it makes viral proteins by the manipulation of ribosomes, the cellular protein synthesis machines in which genetic instructions are converted, or translated, from RNA into proteins. During frameshifting, a ribosome that's translating an RNA "slips" one spot backward or forward along a nucleotide sequence, resulting in the translation of an entirely different protein sequence moving forward. This process essentially nets two proteins for the price of one RNA, and it allows viruses to keep their genomes efficiently compact.

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