Abstract
The current COVID-19 pandemic has highlighted the need for the research community to develop a better understanding of viruses, in particular their modes of infection and replicative lifecycles, to aid in the development of novel vaccines and much needed anti-viral therapeutics. Several viruses express proteins capable of forming pores in host cellular membranes, termed “Viroporins”. They are a family of small hydrophobic proteins, with at least one amphipathic domain, which characteristically form oligomeric structures with central hydrophilic domains. Consequently, they can facilitate the transport of ions through the hydrophilic core. Viroporins localise to host membranes such as the endoplasmic reticulum and regulate ion homeostasis creating a favourable environment for viral infection. Viroporins also contribute to viral immune evasion via several mechanisms. Given that viroporins are often essential for virion assembly and egress, and as their structural features tend to be evolutionarily conserved, they are attractive targets for anti-viral therapeutics. This review discusses the current knowledge of several viroporins, namely Influenza A virus (IAV) M2, Human Immunodeficiency Virus (HIV)-1 Viral protein U (Vpu), Hepatitis C Virus (HCV) p7, Human Papillomavirus (HPV)-16 E5, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Open Reading Frame (ORF)3a and Polyomavirus agnoprotein. We highlight the intricate but broad immunomodulatory effects of these viroporins and discuss the current antiviral therapies that target them; continually highlighting the need for future investigations to focus on novel therapeutics in the treatment of existing and future emergent viruses.
Highlights
Viral protein U (Vpu) inhibits IFN induced STAT1 phosphorylation and downstream INSGoteaxbplyre, stshieonT.MD of Vpu has been shown to be important for promoting virion release from Human Immunodeficiency Virus (HIV)-1 infected cells, while it is dispensable for CD4 degradation [80]
The ORF3a mediated upregulation of Nuclear Factor (NF)-κB and JNK enhances the expression of the chemokine IL-8 in lung epithelial cells, which likely contributes to the pathological Viruses 2021, 13, x FOR PEER RiEnVflIEaWmmation associated with SARS-CoV-1 [269]
The Nuclear magnetic resonance (NMR) structure of polyomavirus JC (JCV) agnoprotein revealed that it possesses a major α-helix which is essential for oligomerisation, a minor α-helix domain, and intrinsically unstructured regions which likely facilitate interaction with diverse partners [275,276]
Summary
Viruses 2021, 13, 2165 basic loop and are further divided into Class IIA with a luminal N and C-terminus and Class IIB with cytosolic termini [4]. CHlaCssVIIpI7viisroapcolraisnssIwIAitvhirthopreoerimn ewmitbhratwneo-stpraannsnminegmdbormanaeindsowmhaiilnes and luminal N and C termini. HPV-16 E5 and SARS-Co-V ORF3a are both class III viroporins with three membVrairnoep-soprainnnsinargedionmvaoilnvsewdhiinlenSuAmRSe-rCoouVs OprRoFc3eassheass adulorninggcytthoeplvasirmailcltiafeil.cycle, but their mainVfiuronpctoiroinnsisarteo irnevgoullvaetde vinirniounmaesrsoeumsbplyroacensdseesgdreusrsinfgrotmhetvhierainl lfiefcetecdycclee,llb[u4t].thTehire mdyasirnegfuunlacttiioonnoifsitoonsrecgaunlaatlseovtirriigognerasthseemacbtliyvaatniodneogfriensfslafmrommasthome iensf,elcetaeddincgeltlo[a4u].toTphhedagyysraengdulaatpioopntoosfisio[n5s].cTahnearlesloeatrsiegogferCtah2+e iaocntsivfarotimonthoef imnflitaomchmonadsorima easn, dleGadoilnggi, otor athuetinopflhuaxgoyf aenxtdraacpeollputloasriCs a[52+].ioTnhse, crealneaaside ovfirCioan2+piroondsufcrtoiomn tahnedmreitloeachseoannddriacaannadlsGoollegaid, otor tahpeopintflosuixs ooff einxfteractceedlluclealrlsC[a62].+ Fiounrtsh, ecramnoaried, vmirainoyn vpirroodpuocrtiinosnaalsnodhrealveeasfeunacntdiocnasninadlseolpeeanddteonatpoof pthtoeisrischoaf ninnfeelcftoerdmcienllgsa[6b]i.liFtyu,ritnhcelrumdionrge,immmanuynveierovpasoiroinnsmaelscohahnaivsemfsu,nsuctcihonass itnhde edpoewnndreengtuolaf ttihoenirofcMhaanjonrelHfiosrtomcionmgpaabtiilbitilyi,tyinCcolumdpinlegxi(mMmHuCn)emeovlaesciuolnesmfreocmhatnhiesmcesll, ssuucrhfaaces tthoeadvoowidnirmegmuulanteiodneotefcMtioanjor[7H–9is]t.oVciormoppoartiinbsiliatryeCeossmenptlieaxl (fMorHthCe) rmeloelaesceuloefsmfraonmy tvhireucseelsl smuarkfaincegttoheamvoaidpiomtemntuianlethdeertaecpteiountic[7t–a9rg].eVt fiororpthoerintrseaatrme eenssteonftiianlfefoctriothues rveilreuassees o[4f].mInadneyevdi,rcuosmespmouankdinsgwthhiecmh balopcokttehnetiiralptohreerfaopremuitnicg tcaarpgaebtilfiotrietsh, esutcrheaatsmreimntaonftaidnifnece-, tairoeubsevinirgusuesse[d4]i.nIcnudrereedn,tctoremaptmouendt stwrahteicghiebsl[o1c0k].their pore forming capabilities, such as rimantadine, are being used in current treatment strategies [10].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
