Small protein offers big insight into FMD virus

Polyprotein found to play major role in replication of foot and mouth disease virus and may lead to more effective vaccines.

Scientists in the U.K. have determined that a tiny protein that plays a major role in the replication of foot and mouth disease (FMD) virus demonstrates a greater level of genetic economy than previously reported.

Researchers from the University of Leeds and The Pirbright Institute identified a new role for a small viral protein -- called 3B3 -- that reveals how these viruses can copy themselves efficiently. FMD is an animal pathogen of great economic importance, and the findings could lead to the development of more effective vaccines against the disease in the future.

Positive-strand RNA viruses are generally typified by a small genome size. To compensate for this limitation, they have evolved ways of multiplying the functions achievable from a small genome, thus increasing their "genetic economy." In the picornavirus family of RNA viruses, the viral proteins are produced via a series of transient precursors, which are believed to possess additional functions required for virus replication beyond those of the fully processed proteins.

The researchers showed that the small 3B3 protein from the FMD virus is key in directing the processing pathways of the P3 polyprotein to facilitate release of the viral polymerase. This is in addition to, and independent from, the role of 3B3 as a primer for replication.

Such strategies to maximize genetic economy are not limited to the picornavirus family and are thought to be utilized by a wide range of RNA viruses to expand the functional potential of limited genome sizes.

Members of the picornavirus family include several well-known human pathogens such as poliovirus and important animal pathogens such as FMD virus -- the causative agent of FMD, an acute vesicular disease of cloven-hoofed ruminants that is endemic in many parts of the world.

This study exemplifies how multiple functions within one small viral protein can control viral replication and demonstrates a new level of genetic economy in the picornaviruses. Furthermore, systems that provide "help" in trans to assist replication have the potential to be exploited for the production of attenuated vaccines (e.g., using "helper" cell lines).

The researchers said they are now in the process of investigating how mutations at polyprotein processing boundaries may be used for producing attenuated vaccines.

Lead researcher professor Nicola Stonehouse from the University of Leeds Faculty of Biological Sciences said, "By understanding the role of this tiny viral protein in the replication of foot and mouth disease virus, we're hoping to find more effective vaccines that fight the disease."

The research was funded by the Biotechnology & Biological Sciences Research Council. The findings were published online in the journal PLOS Pathogens and are available at https://doi.org/10.1371/journal.ppat.1006666.

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