Viruses Create New Human-Virus Genes

Viruses Create New Human-Virus Genes
By Forging Our Genetic Code

A novel mechanism that allows viruses to produce unexpected proteins is unveiled in a new study published in the journal Cell, where researchers have shown that a large group of viruses can expand their own genomes by stealing genetic signals from their hosts.

Researchers at the Global Health and Emerging Pathogens Institute at the Icahn School of Medicine at Mount Sinai in New York, led the cross-disciplinary collaborative study, along with the researchers from MRC-University of Glasgow Centre for Virus Research, United Kingdom.

Segmented negative-strand RNA viruses (sNSVs), a vast group of viruses which include widespread and dangerous pathogens of plants, domesticated animals, and humans, including the Lass virus and the influenza viruses, were studied by the cross-disciplinary team of virologists.

The researchers showed in the study that viruses steal the genetic signals from their hosts and produce a vast amount of previously undetected proteins. As these proteins are encoded by stitching together the host and viral sequences, the researchers labeled them as UFO (Upstream Frankenstein Open reading frame) proteins. Prior to this study, the existence of these kinds of proteins was completely unknown. These UFO proteins could be exploited for

vaccine purposes and can alter the course of viral infection.

The corresponding author on the study, an Associate Professor of Microbiology at Icahn School of Medicine, Ivan Marazzi, Ph.D. said, “The expression of pathogen-derived proteins shows the capacity of a pathogen to overcome host barriers and establish infection. We need to have a clear understanding of what proteins a pathogen encodes, the manner in which they contribute to virulence, and how they function, in order to understand how a pathogen antagonizes the host and establishes infection.”

Viruses need to provide suitable instructions to the protein-building machinery in their host’s cells as they cannot build their own proteins. Viruses do this through a process known as “cap-snatching,” in which, from one of the cell’s own protein-encoding messages (mRNA, or a messenger), the viruses cut the end and then with a copy of one of their own genes, that sequence is extended, giving a hybrid message to be read.

Dr. Marazzi said, “Our work shows that the host sequence is not silent, as for decades we thought that the body is reading a message provided to it solely by the virus when the body encounters the signal to start translating that message into protein (a ‘start codon’).”

The researchers show that viruses (sNSVs) can produce messages with extra, host-derived start codons, a process they called “start snatching,” because they make hybrids of host mRNAs with their own genes. Translating proteins from the hybrid host-virus sequences that were previously unsuspected is made possible by this. It was shown further that potentially a vast number of viruses and influenza viruses express these novel genes. The product of these hybrid genes can modulate virulence and can be visible to the immune system.

A research fellow at MRC-University of Glasgow Centre for Virus Research, and corresponding author, Ed Hutchinson, Ph.D. said, “Some viruses can wring every last bit of potential out of the host’s molecular machinery they are exploiting as new ways to do this are identified by them as the viruses take over their host at the molecular level. This implies that a huge number of viral species can make previously unsuspected genes, though the work is done here focusses on influenza viruses.”

Understanding the distinct roles the unsuspected genes play is the next part of the work, said the researchers. Dr. Marazzi said, “We can study them and apply the knowledge gained to help in eradicating diseases, now that we know they exist. These new insights may lead to identifying novel ways to stop the viral epidemics and pandemics, as a large global effort is required to stop them.”

The UK Medical Research Council,  and the National Institute of Allergy and Infectious Diseases supported the study by providing funding.

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Viruses Create New Human-Virus Genes