Synthesis and Translation of Viral mRNA in Reovirus-Infected Cells: Progress and Remaining Questions

Abstract

At the end of my doctoral studies, in 1988, I published a review article on the major steps of transcription and translation during the mammalian reovirus multiplication cycle, a topic that still fascinates me 30 years later. It is in the nature of scientific research to generate further questioning as new knowledge emerges. Our understanding of these fascinating viruses thus remains incomplete but it seemed appropriate at this moment to look back and reflect on our progress and most important questions that still puzzle us. It is also essential of being careful about concepts that seem so well established, but could still be better validated using new approaches. I hope that the few reflections presented here will stimulate discussions and maybe attract new investigators into the field of reovirus research. Many other aspects of the viral multiplication cycle would merit our attention. However, I will essentially limit my discussion to these central aspects of the viral cycle that are transcription of viral genes and their phenotypic expression through the host cell translational machinery. The objective here is not to review every aspect but to put more emphasis on important progress and challenges in the field.

Function, Architecture, and Biogenesis of Reovirus Replication Neoorganelles

“…Viral translation also is enhanced by the reovirus σ3 outer-capsid protein [46]. The σ3 protein binds dsRNA during infection, blocking the activation of protein kinase RNA-activated (PKR), an interferon-induced enzyme that is activated by binding to dsRNA [47].…”

How Many Mammalian Reovirus Proteins are involved in the Control of the Interferon Response?

“…The outer capsid is then added, coinciding with the arrest of transcriptional activity. For a detailed review on transcription and translation during the viral multiplication cycle, the reader is referred to a recent review [9].…”

“…This is exerted through the action of interferon-stimulated factors, mainly due to the action of IFIT proteins [15,16,17,18,19]. Interestingly, it has been reported that part of viral mRNA is devoid of a cap structure late in infection, rather harboring a monophosphate end, although the transient presence of a diphosphorylated end is possible [20,21,22] (for a recent review on reovirus mRNA structure and synthesis, see [9]). Finally, in the related rotavirus, it was more recently shown that a fraction of the RNA is not completely capped, and this seems to be responsible for recognition by the sensor RIG-I [23].…”

Recognition of Reovirus RNAs by the Innate Immune System

“…Within the cytoplasm, the core is transcriptionally active. The encapsidated RNA-dependent RNA polymerases use each genome segment as a template to produce mRNAs [3]. These mRNAs, which are capped by the viral capping enzymes also present in the particle, are extruded through turrets in the core into the cytoplasm, for translation by host ribosomes.…”