Potential Viroporin Candidates From Pathogenic Viruses Using Bacteria-Based Bioassays

Prabhat Pratap Singh Tomar,Rivka Oren,Miriam Krugliak,Isaiah T Arkin

doi:10.3390/v11070632

Abstract

Viroporins are a family of small hydrophobic proteins found in many enveloped viruses that are capable of ion transport. Building upon the ability to inhibit influenza by blocking its archetypical M2 H+ channel, as a family, viroporins may represent a viable target to curb viral infectivity. To this end, using three bacterial assays we analyzed six small hydrophobic proteins from biomedically important viruses as potential viroporin candidates. Our results indicate that Eastern equine encephalitis virus 6k, West Nile virus MgM, Dengue virus 2k, Dengue virus P1, Variola virus gp170, and Variola virus gp151 proteins all exhibit channel activity in the bacterial assays, and as such may be considered viroporin candidates. It is clear that more studies, such as patch clamping, will be needed to characterize the ionic conductivities of these proteins. However, our approach presents a rapid procedure to analyze open reading frames in other viruses, yielding new viroporin candidates for future detailed investigation. Finally, if conductivity is proven vital to their cognate viruses, the bio-assays presented herein afford a simple approach to screen for new channel blockers.

Highlights

Many important viruses have been shown to contain small hydrophobic proteins that are capable of ion channel activity
Protein sequences from Eastern equine encephalitis virus, West Nile virus, Dengue virus, and Variola virus were extracted from the NCBI database
Using Phobius, a combined transmembrane topology and signal peptide predictor [39,40], we found six viroporin candidates listed in Table 1 and shown schematically in Figure 1 according to their predicted topology

Summary

Introduction

Many important viruses have been shown to contain small hydrophobic proteins that are capable of ion channel activity. Members of this family have been collectively termed viroporins [1,2,3,4,5,6]. The best-characterized member of the viroporin family is the influenza M2 channel [7,8]. Influenza A M2 is a single-pass membrane protein that homo-tetramerizes to form the active protein complex [11]. Since other viroporins are thought to possess a single transmembrane stretch, they may adopt a helical bundle structure, akin to the structure of M2

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Conclusion