Vaccinia Virus’s VIP Access to Host Protein Making Machinery

Viruses require a host cell to reproduce. Because viruses are so small, they don’t have all the machinery required to achieve reproduction like unicellular organisms (bacteria/archaea) or multicellular organisms, like humans. Unfortunately for us, viruses that infect human cells use us as viral factories to make new “baby-viruses” for them, and usually causing damage to us in the process.

Poxviruses are large by virus standards but they still need help to replicate in human hosts. Variola virus, the infectious cause of smallpox, was a particularly devastating poxvirus. As recently as 1967 the World Health Organization estimated that 15 million people contracted the disease and that 2 million died from it that year. Following a successful global vaccination campaign using a related poxvirus known as vaccinia virus, variola virus was eradicated and no smallpox cases have been recorded in decades.

Viruses do not get priority passes to the cellular machinery that they rely upon. Rather, they must compete with the host for access to host cell protein-making machines. Actually, it’s even worse than that, because our cells have evolved to ‘sense’ that they’re infected and turn off protein synthesis to circumvent viral replication. Many viruses have evolved mechanisms to undermine these surveillance mechanisms, and gain priority access to the protein synthesis machinery. Dhungel and colleagues recently discovered a new feature of poxviruses that allows them to commandeer the host machinery.

Screen Shot 2017-09-28 at 10.34.26 AMBut first, a short biology lesson. If you don’t remember, the central dogma of molecular biology goes like this:

DNA is transcribed into RNA which is then translated into an amino acid chain (otherwise known as a protein). The RNA, referred to as messenger RNA, is utilized to make proteins. This process can get more complicated (see “special” in the figure) but the general flow of information in biological systems is DNA to RNA to protein.

Dhungel et al. found that vaccinia virus messenger RNAs have unique sequences at their ends that allow them to “cut the line” and be the first to be “translated” into protein. It appears that these viral sequences act in a completely unique fashion that has not been observed before. More work will need to be done to figure out precisely how the sequence helps this model poxvirus gain priority access and efficiently decode viral mRNAs into proteins.

This research advances our basic understanding of poxvirus biology, and reveals new molecular targets that might be exploited for antiviral drug discovery. Many dangerous infections are caused by poxviruses and understanding how these viruses commandeer human cells can help us identify new ways to slow its progress.

Summary written by: Landon Getz

To read the full paper, please click the following link:

The 5′-poly(A) leader of poxvirus mRNA confers a translational advantage that can be achieved in cells with impaired cap-dependent translation

Pragyesh Dhungel, Shuai Cao, Zhilong Yang

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