Researchers have shown that a large group of viruses, including influenza viruses and other pathogens, steal host genetic signals to expand their own genomes.
The study was recently published in Cell and was a collaboration between the University of Glasgow and researchers at Icahn School of Medicine at Mount Sinai in New York. The study showed that viruses can produce a wealth of previously undetected proteins by stealing host genetic signals.
The new proteins, called “UFOs”, short for Upstream Frankenstein Open reading frame proteins are a novel finding. The UFO proteins are encoded by stitching together the host and viral sequences and can alter the viral infection, so they can be exploited for vaccine development.
To find these proteins, the researchers looked at a large group of viruses, segmented negative-strand RNA viruses (sNSVs). Viruses use host cells to build proteins through a process called “cap-snatching”, where one end of the cells mRNA is cut and the sequence is extended with a copy of viral genes – resulting in a hybrid message to be read.
Ivan Marazzi, Associate Professor of Microbiology at Icahn School of Medicine and co-corresponding author of the study said “The capacity of a pathogen to overcome host barriers and establish infection is based on the expression of pathogen derived proteins. To understand how a pathogen antagonises the host and establishes infection, we need to have a clear understanding of what proteins a pathogen encodes, how they function and the manner in which they contribute to virulence”.
He adds: “For decades we thought that by the time the body encounters the signal to start translating that message into protein (a ‘start codon’) it is reading a message provided to it solely by the virus. Our work shows that the host sequence is not silent.”
The study showed that because the viruses make hybrids of host mRNAs with their own genes, the sNSVs can produce messages with extra start codons derived from the host, a process called “start snatching”, which makes it possible to translate unsuspected proteins from the hybrid host-virus sequences.
The study showed that the novel genes are expressed in influenza viruses and potentially a vast number of other pathogens. In addition that the product of these genes are detectable to the immune system and can modulate virulence.
More research is needed to understand these proteins and what the implications of them are in future epidemics or pandemics. The researchers say the next part of their work will be to study the distinct roles of the unsuspected genes.
Dr Marazzi said that now we know they exist, we can study these “UFOs” and use the knowledge to help disease eradication.
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