Emerging Roles of Viroporins Encoded by DNA Viruses: Novel Targets for Antivirals?

Jamie Royle,Marietta Müller,Samuel Dobson,Andrew Macdonald

doi:10.3390/v7102880

Jamie Royle, Marietta Müller + Show 2 more

Open Access

https://doi.org/10.3390/v7102880

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Abstract

Studies have highlighted the essential nature of a group of small, highly hydrophobic, membrane embedded, channel-forming proteins in the life cycles of a growing number of RNA viruses. These viroporins mediate the flow of ions and a range of solutes across cellular membranes and are necessary for manipulating a myriad of host processes. As such they contribute to all stages of the virus life cycle. Recent discoveries have identified proteins encoded by the small DNA tumor viruses that display a number of viroporin like properties. This review article summarizes the recent developments in our understanding of these novel viroporins; describes their roles in the virus life cycles and in pathogenesis and speculates on their potential as targets for anti-viral therapeutic intervention.

Highlights

IntroductionViruses have evolved a myriad of strategies to manipulate the host cell environment to one that is conducive for virus replication
As obligate intracellular parasites, viruses have evolved a myriad of strategies to manipulate the host cell environment to one that is conducive for virus replication
Whilst high-resolution structural information is currently only available for a limited number of viroporins [4,5,6,7,8], a bio-informatic approach has often been successfully employed to identify key features in viroporins that lack any structural information [1,3]. Their small size necessitates that viroporins must oligomerize in membranes to form an active channel complex. Formation of these high-order complexes is often observed in mild detergents such as 1,2-diheptanoyl-sn-glycero-3-phosphocholine (DHPC) [3,9] and is likely to be mediated by hydrophobic interactions between the transmembrane domains (TMD) of each monomer; in some viroporins basic residues adjacent to the TMD may facilitate membrane binding and insertion [10,11]

Summary

Introduction

Viruses have evolved a myriad of strategies to manipulate the host cell environment to one that is conducive for virus replication. Whilst high-resolution structural information is currently only available for a limited number of viroporins [4,5,6,7,8], a bio-informatic approach has often been successfully employed to identify key features in viroporins that lack any structural information [1,3] Their small size necessitates that viroporins must oligomerize in membranes to form an active channel complex. Modulation of ionic homeostasis within specific cellular compartments allows for viroporins to manipulate a wide range of cellular processes from autophagy [13,14,15], trafficking [16,17], inflammation [18,19], transformation [3] to cell survival [20] Due to these broad perturbations to host cell physiology, it is not surprising that viroporin function has been shown to assist in all stages of the virus life cycle including entry, membrane penetration, genome replication and virus egress [1,2]. This review will summarize our understanding of these putative viroporins, describe their known functions and attempt to highlight how possible ion channel activity may aid the life cycles of these small DNA tumor viruses

Polyomaviruses

JC Virus Agnoprotein

Papillomaviruses

HPV16 E5

Findings

Concluding Remarks