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Vaccinia Virus as a Master of Host Shutoff Induction: Targeting Processes of the Central Dogma and Beyond

Division of Biology, Kansas State University, Manhattan, KS 66506, USA
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Authors to whom correspondence should be addressed.
Current address: Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Pathogens 2020, 9(5), 400; https://doi.org/10.3390/pathogens9050400
Received: 28 April 2020 / Revised: 18 May 2020 / Accepted: 19 May 2020 / Published: 21 May 2020
(This article belongs to the Special Issue Poxviruses: Novel Concepts and Emerging Trends)
The synthesis of host cell proteins is adversely inhibited in many virus infections, whereas viral proteins are efficiently synthesized. This phenomenon leads to the accumulation of viral proteins concurrently with a profound decline in global host protein synthesis, a phenomenon often termed “host shutoff”. To induce host shutoff, a virus may target various steps of gene expression, as well as pre- and post-gene expression processes. During infection, vaccinia virus (VACV), the prototype poxvirus, targets all major processes of the central dogma of genetics, as well as pre-transcription and post-translation steps to hinder host cell protein production. In this article, we review the strategies used by VACV to induce host shutoff in the context of strategies employed by other viruses. We elaborate on how VACV induces host shutoff by targeting host cell DNA synthesis, RNA production and processing, mRNA translation, and protein degradation. We emphasize the topics on VACV’s approaches toward modulating mRNA processing, stability, and translation during infection. Finally, we propose avenues for future investigations, which will facilitate our understanding of poxvirus biology, as well as fundamental cellular gene expression and regulation mechanisms. View Full-Text
Keywords: poxviruses; vaccinia virus; virus–host interactions; host shutoff; transcription; mRNA processing; translation; central dogma poxviruses; vaccinia virus; virus–host interactions; host shutoff; transcription; mRNA processing; translation; central dogma
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Dhungel, P.; Cantu, F.M.; Molina, J.A.; Yang, Z. Vaccinia Virus as a Master of Host Shutoff Induction: Targeting Processes of the Central Dogma and Beyond. Pathogens 2020, 9, 400.

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