Dr Stephen Berryman and Dr Toby Tuthill from The Pirbright Institute have collaborated with the MRC Laboratory of Molecular Biology and other research institutes to uncover a system used by foot-and-mouth disease virus (FMDV) to prevent antiviral signalling of infected cells. The discovery could allow scientists to detect animals that have been infected with FMDV and distinguish them from those that have been vaccinated.
The research, published in Proceedings of the National Academy of Sciences describes a novel process that FMDV uses to counter the antiviral protein ISG15, which is produced by infected cells and attaches to the virus proteins to stop replication.
The scientists discovered that FMDV encodes a protein called Lbpro which deactivates ISG15 by cutting it into distinctive pieces, allowing the virus to continue replicating unhindered. Importantly, one of the ISG15 pieces left behind – a GlyGly motif – can be detected, and could potentially be used as a biomarker to indicate that an animal is infected.
Dr Toby Tuthill, head of the Picornavirus Molecular Biology group, said: “Discovering the unique interaction between Lbpro and ISG15 has given us new insights into the arms race between the host and FMDV. One of the more exciting opportunities it presents us with is the possibility of using GlyGly for the purpose of detection, the key advantage being that GlyGly is only made when an animal is infected by FMDV. An animal that has been vaccinated will not create GlyGly and therefore could allow the two to be distinguished.”
It is essential that countries vaccinating against FMD are able to discriminate between vaccinated and infected animals in order to maintain their ability to trade. Providing another method that can accurately determine if herds are infected could improve the ability of vaccinating countries to trade.
Article: Irreversible inactivation of ISG15 by a viral leader protease enables alternative infection detection strategies by Kirby N. Swatek, Martina Aumayr, Jonathan N. Pruneda, Linda J. Visser, Stephen Berryman, Anja F. Kueck, Paul P. Geurink, Huib Ovaa, Frank J. M. van Kuppeveld, Tobias J. Tuthill, Tim Skern, and David Komander, published in Proceedings of the National Academy of Sciences, online 20 February 2018, doi: 10.1073/pnas.1710617115