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Proc Natl Acad Sci U S A
2017 Jan 31;1145:1147-1152. doi: 10.1073/pnas.1614955114.
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Hepatitis E virus ORF3 is a functional ion channel required for release of infectious particles.
Ding Q
,
Heller B
,
Capuccino JM
,
Song B
,
Nimgaonkar I
,
Hrebikova G
,
Contreras JE
,
Ploss A
.
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Hepatitis E virus (HEV) is the leading cause of enterically transmitted viral hepatitis globally. Of HEV's three ORFs, the function of ORF3 has remained elusive. Here, we demonstrate that via homophilic interactions ORF3 forms multimeric complexes associated with intracellular endoplasmic reticulum (ER)-derived membranes. HEV ORF3 shares several structural features with class I viroporins, and the function of HEV ORF3 can be maintained by replacing it with the well-characterized viroporin influenza A virus (IAV) matrix-2 protein. ORF3's ion channel function is further evidenced by its ability to mediate ionic currents when expressed in Xenopus laevis oocytes. Furthermore, we identified several positions in ORF3 critical for its formation of multimeric complexes, ion channel activity, and, ultimately, release of infectious particles. Collectively, our data demonstrate a previously undescribed function of HEV ORF3 as a viroporin, which may serve as an attractive target in developing direct-acting antivirals.
,
Correction for Ding et al., Hepatitis E virus ORF3 is a functional ion channel required for release of infectious particles.
2017, Pubmed
,
Correction for Ding et al., Hepatitis E virus ORF3 is a functional ion channel required for release of infectious particles.
2017,
Pubmed
Ahmad,
Molecular virology of hepatitis E virus.
2011,
Pubmed
Cao,
Molecular biology and replication of hepatitis E virus.
2012,
Pubmed
Colson,
Hepatitis E virus as a newly identified cause of acute viral hepatitis during human immunodeficiency virus infection.
2008,
Pubmed
Colson,
Hepatitis E in an HIV-infected patient.
2009,
Pubmed
Cordes,
Bundles consisting of extended transmembrane segments of Vpu from HIV-1: computer simulations and conductance measurements.
2002,
Pubmed
Dalton,
Persistent carriage of hepatitis E virus in patients with HIV infection.
2009,
Pubmed
Dalton,
Hepatitis E: an emerging infection in developed countries.
2008,
Pubmed
Debing,
Hepatitis E virus mutations associated with ribavirin treatment failure result in altered viral fitness and ribavirin sensitivity.
2016,
Pubmed
Emerson,
ORF3 protein of hepatitis E virus is not required for replication, virion assembly, or infection of hepatoma cells in vitro.
2006,
Pubmed
Emerson,
Release of genotype 1 hepatitis E virus from cultured hepatoma and polarized intestinal cells depends on open reading frame 3 protein and requires an intact PXXP motif.
2010,
Pubmed
Ewart,
Amiloride derivatives block ion channel activity and enhancement of virus-like particle budding caused by HIV-1 protein Vpu.
2002,
Pubmed
Feng,
A pathogenic picornavirus acquires an envelope by hijacking cellular membranes.
2013,
Pubmed
Foster,
Resistance mutations define specific antiviral effects for inhibitors of the hepatitis C virus p7 ion channel.
2011,
Pubmed
Hay,
The molecular basis of the specific anti-influenza action of amantadine.
1985,
Pubmed
Holsinger,
Influenza A virus M2 ion channel protein: a structure-function analysis.
1994,
Pubmed
,
Xenbase
Ishikawa,
STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling.
2008,
Pubmed
Iwatsuki-Horimoto,
The cytoplasmic tail of the influenza A virus M2 protein plays a role in viral assembly.
2006,
Pubmed
Jones,
Hepatitis C virus p7 and NS2 proteins are essential for production of infectious virus.
2007,
Pubmed
Kamar,
Ribavirin therapy inhibits viral replication on patients with chronic hepatitis e virus infection.
2010,
Pubmed
Kamar,
Hepatitis E virus and chronic hepatitis in organ-transplant recipients.
2008,
Pubmed
Kenney,
The PSAP motif within the ORF3 protein of an avian strain of the hepatitis E virus is not critical for viral infectivity in vivo but plays a role in virus release.
2012,
Pubmed
Kenney,
Replacement of the hepatitis E virus ORF3 protein PxxP motif with heterologous late domain motifs affects virus release via interaction with TSG101.
2015,
Pubmed
Li,
Efficient genetic manipulation of the NOD-Rag1-/-IL2RgammaC-null mouse by combining in vitro fertilization and CRISPR/Cas9 technology.
2014,
Pubmed
Lu,
Severe acute respiratory syndrome-associated coronavirus 3a protein forms an ion channel and modulates virus release.
2006,
Pubmed
,
Xenbase
Mallet,
Brief communication: case reports of ribavirin treatment for chronic hepatitis E.
2010,
Pubmed
Nagashima,
A PSAP motif in the ORF3 protein of hepatitis E virus is necessary for virion release from infected cells.
2011,
Pubmed
Nieva,
Viroporins: structure and biological functions.
2012,
Pubmed
Pavlović,
The hepatitis C virus p7 protein forms an ion channel that is inhibited by long-alkyl-chain iminosugar derivatives.
2003,
Pubmed
Pinto,
Influenza virus M2 protein has ion channel activity.
1992,
Pubmed
,
Xenbase
Schildgen,
Chronic hepatitis E and organ transplants.
2008,
Pubmed
Shukla,
Cross-species infections of cultured cells by hepatitis E virus and discovery of an infectious virus-host recombinant.
2011,
Pubmed
Steinmann,
Antiviral effects of amantadine and iminosugar derivatives against hepatitis C virus.
2007,
Pubmed
Steinmann,
Hepatitis C virus p7 protein is crucial for assembly and release of infectious virions.
2007,
Pubmed
Surjit,
Enhanced alpha1 microglobulin secretion from Hepatitis E virus ORF3-expressing human hepatoma cells is mediated by the tumor susceptibility gene 101.
2006,
Pubmed
Suzuki,
The human polyoma JC virus agnoprotein acts as a viroporin.
2010,
Pubmed
Sze,
Viral Membrane Channels: Role and Function in the Virus Life Cycle.
2015,
Pubmed
Takahashi,
Monoclonal antibodies raised against the ORF3 protein of hepatitis E virus (HEV) can capture HEV particles in culture supernatant and serum but not those in feces.
2008,
Pubmed
Terwilliger,
Functional role of human immunodeficiency virus type 1 vpu.
1989,
Pubmed
Tyagi,
The ORF3 protein of hepatitis E virus interacts with liver-specific alpha1-microglobulin and its precursor alpha1-microglobulin/bikunin precursor (AMBP) and expedites their export from the hepatocyte.
2004,
Pubmed
Wilson,
Hexamethylene amiloride blocks E protein ion channels and inhibits coronavirus replication.
2006,
Pubmed
Yamada,
ORF3 protein of hepatitis E virus is essential for virion release from infected cells.
2009,
Pubmed
Yin,
Distinct Entry Mechanisms for Nonenveloped and Quasi-Enveloped Hepatitis E Viruses.
2016,
Pubmed
Yin,
Role of Envelopment in the HEV Life Cycle.
2016,
Pubmed
Zafrullah,
The ORF3 protein of hepatitis E virus is a phosphoprotein that associates with the cytoskeleton.
1997,
Pubmed
Zhang,
Long-term efficacy of a hepatitis E vaccine.
2015,
Pubmed
