New study reveals that arteriviruses may produce more proteins than previously understood

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A recently published study in the Proceedings of the National Academy of Sciences has revealed that arteriviruses, particularly the Simian hemorrhagic fever virus (SHFV), may actually produce more mRNAs and proteins than previously reported. This finding could provide insight into how the virus may potentially evolve in the future to infect humans.

Margo A Brinton (Georgia State University, GA, USA), the corresponding author of the study, explained: “This virus currently doesn’t infect chimpanzees or humans, but it’s one of the viruses that’s recently been put on a list of possible emerging viruses that could evolve to infect chimpanzees and/or humans in the future.” He added that: “No one understands what is restricting the host range of this virus so precisely. SHFV is in the same virus group as several viruses that cause important agricultural diseases and is also related to the severe acute respiratory syndrome virus.”

According to previous research, only nine transcription regulatory sequences (TRSs) have been reported in SHFV.  However, in the present study, researchers used next-generation sequencing to identify 96 SHFV body TRSs. They also found that these TRSs were used by the virus to produce subgenomic messenger RNAs (sg mRNAs) in both SHFV-infected kidney cells and white blood cells of macaques.

“TRSs regulate the production of the templates for the sg mRNAs from the genome RNA,” Brinton commented. “The wisdom was that there was one primary TRS for each structural gene. Using next-generation sequencing to obtain a very deep analysis of all the sg mRNAs that were made in the infected cells, we found that there were multiple TRSs for many of the structural proteins (a maximum of 11) and they all produced sg mRNAs. People thought that the few additional TRSs found previously were just backups and weren’t used unless the primary one was inactivated by mutation, but our data show they’re all always used.”

In addition, the researchers also discovered that some TRSs generated sg mRNAs with a different reading frame than the genome one – indicating that previously unknown proteins could be produced and that the virus could possibly produce more proteins than previously understood. They also found that a number of sg mRNAs produced only the terminal fragment of a known viral protein.

To test the function of these fragments, Brinton and colleagues “knocked out their production in infected cells one at a time by mutation each start code for translation.” Brinton added that: “Less virus was produced when two of these fragments were not produced, suggesting that at least some of these small proteins are functionally important.”

“The functions of the newly discovered viral proteins are unknown. There’s s till a lot more we have to learn to understand how these viral proteins manipulate the infected cell and/or regulate viral replication,” Brinton concluded.

Sources: Di H, Madden JC Jr, Morantz EK et al. Expanded subgenomic mRNA transcriptome and coding capacity of a nidovirus. Proc. Natl Acad. Sci. USA 114(42), E8895–E8904 (2017); www.sciencedaily.com/releases/2017/10/171016122112.htm

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