Virus–Host Cell Interplay during Hepatitis E Virus Infection

Wissing, Michael; Brüggemann, Yannick; Steinmann, Eike; Todt, Daniel

doi:10.1016/j.tim.2020.07.002

Cited by 47 publications

(49 citation statements)

References 89 publications

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“…Finally, the multivesicular bodies fuse with the plasma membrane, and the virions are released from liver cells either into the bloodstream wrapped with a lipid membrane (eHEV), or in the bile duct where the quasi-envelope is degraded by bile salts [22] . In-depth reviews on interactions between viral and host cell factors during HEV infection can be found elsewhere [93] . The underlying molecular mechanisms in several steps of HEV life cycle, especially the entry, uncoating, assembly and release steps, remain poorly understood.…”

Section: Life Cycle Of Hev Replicationmentioning

confidence: 99%

Structural and molecular biology of hepatitis E virus

Wang

Meng

2021

Computational and Structural Biotechnology Journal

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Hepatitis E virus (HEV) is one of the most common causes of acute viral hepatitis, mainly transmitted by fecal-oral route but has also been linked to fulminant hepatic failure, chronic hepatitis, and extrahepatic neurological and renal diseases. HEV is an emerging zoonotic pathogen with a broad host range, and strains of HEV from numerous animal species are known to cross species barriers and infect humans. HEV is a single-stranded, positive-sense RNA virus in the family Hepeviridae . The genome typically contains three open reading frames (ORFs): ORF1 encodes a nonstructural polyprotein for virus replication and transcription, ORF2 encodes the capsid protein that elicits neutralizing antibodies, and ORF3, which partially overlaps ORF2, encodes a multifunctional protein involved in virion morphogenesis and pathogenesis. HEV virions are non-enveloped spherical particles in feces but exist as quasi-enveloped particles in circulating blood. Two types of HEV virus-like particles (VLPs), small T = 1 (270 Å) and native virion-sized T = 3 (320–340 Å) have been reported. There exist two distinct forms of capsid protein, the secreted form (ORF2 S ) inhibits antibody neutralization, whereas the capsid-associated form (ORF2 C ) self-assembles to VLPs. Four cis -reactive elements (CREs) containing stem-loops from secondary RNA structures have been identified in the non-coding regions and are critical for virus replication. This mini-review discusses the current knowledge and gaps regarding the structural and molecular biology of HEV with emphasis on the virion structure, genomic organization, secondary RNA structures, viral proteins and their functions, and life cycle of HEV.

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Section: Life Cycle Of Hev Replicationmentioning

confidence: 99%

Structural and molecular biology of hepatitis E virus

Wang

Meng

2021

Computational and Structural Biotechnology Journal

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“…Furthermore, the lack of a robust HEV cell culture models has hampered the development of new antiviral HEV drug candidates. Only little is known about potential virus‐host interaction partners 111 . A newly developed system raises hope, that this fact will be banned from future articles and new leverage points for intervention strategies can be identified 112 .…”

Section: Treatment Optionsmentioning

confidence: 99%

Hepatitis E: An update on One Health and clinical medicine

Velavan

Pallerla

Johne

et al. 2021

Liver International

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The hepatitis E virus (HEV) is one of the main causes of acute hepatitis and the de facto global burden is underestimated. HEV‐related clinical complications are often undetected and are not considered in the differential diagnosis. Convincing findings from studies suggest that HEV is clinically relevant not only in developing countries but also in industrialized countries. Eight HEV genotypes (HEV‐1 to HEV‐8) with different human and animal hosts and other HEV‐related viruses are in circulation. Transmission routes vary by genotype and location, with large waterborne outbreaks in developing countries and zoonotic food‐borne infections in developed countries. An acute infection can be aggravated in pregnant women, organ transplant recipients, patients with pre‐existing liver disease and immunosuppressed patients. HEV during pregnancy affects the fetus and newborn with an increased risk of vertical transmission, preterm and stillbirth, neonatal jaundice and miscarriage. Hepatitis E is associated with extrahepatic manifestations that include neurological disorders such as neuralgic amyotrophy, Guillain‐Barré syndrome and encephalitis, renal injury and haematological disorders. The risk of transfusion‐transmitted HEV is increasingly recognized in Western countries where the risk may be because of a zoonosis. RNA testing of blood components is essential to determine the risk of transfusion‐transmitted HEV. There are currently no approved drugs or vaccines for HEV infections. This review focuses on updating the latest developments in zoonoses, screening and diagnostics, drugs in use and under development, and vaccines.

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“…Some viruses take advantage of the electrostatic interactions between the negatively charged sulfated HS chains and the basic residues of their surface or capsid proteins to increase their concentration at the host cell surface, thus enhancing their binding to specific entry receptors [ 24 , 25 ]. Table 1 lists the viruses whose infection in the human organism is strictly dependent on their ability to bind the cell surface HSPGs [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ].…”

Section: Molecular Mechanisms By Which Viruses Exploit Heparan Sulfate Proteoglycans To Infect Host Cellsmentioning

confidence: 99%

“…In particular, syndecan-1 and syndecan-4 serve as major cellular factors for HCV attachment to hepatocytes [ 45 , 46 ]. The binding of the major capsid protein, pORF2, to the HSPGs, specifically syndecans, leads to hepatitis E virus (HEV) enrichment on the cell surface, allowing subsequent interaction with entry receptors [ 49 , 50 ]. The respiratory pathogen human metapneumovirus (HMPV) uses HSPGs to bind to target cells and undergoes clathrin-mediated endocytosis and membrane fusion in endosomes.…”

Section: Molecular Mechanisms By Which Viruses Exploit Heparan Sulfate Proteoglycans To Infect Host Cellsmentioning

confidence: 99%

Heparan Sulfate Proteoglycans in Viral Infection and Treatment: A Special Focus on SARS-CoV-2

Pasquale

Quiccione

Tafuri

et al. 2021

IJMS

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Heparan sulfate proteoglycans (HSPGs) encompass a group of glycoproteins composed of unbranched negatively charged heparan sulfate (HS) chains covalently attached to a core protein. The complex HSPG biosynthetic machinery generates an extraordinary structural variety of HS chains that enable them to bind a plethora of ligands, including growth factors, morphogens, cytokines, chemokines, enzymes, matrix proteins, and bacterial and viral pathogens. These interactions translate into key regulatory activity of HSPGs on a wide range of cellular processes such as receptor activation and signaling, cytoskeleton assembly, extracellular matrix remodeling, endocytosis, cell-cell crosstalk, and others. Due to their ubiquitous expression within tissues and their large functional repertoire, HSPGs are involved in many physiopathological processes; thus, they have emerged as valuable targets for the therapy of many human diseases. Among their functions, HSPGs assist many viruses in invading host cells at various steps of their life cycle. Viruses utilize HSPGs for the attachment to the host cell, internalization, intracellular trafficking, egress, and spread. Recently, HSPG involvement in the pathogenesis of SARS-CoV-2 infection has been established. Here, we summarize the current knowledge on the molecular mechanisms underlying HSPG/SARS-CoV-2 interaction and downstream effects, and we provide an overview of the HSPG-based therapeutic strategies that could be used to combat such a fearsome virus.

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Virus–Host Cell Interplay during Hepatitis E Virus Infection

Cited by 47 publications

References 89 publications

Structural and molecular biology of hepatitis E virus

Structural and molecular biology of hepatitis E virus

Hepatitis E: An update on One Health and clinical medicine

Heparan Sulfate Proteoglycans in Viral Infection and Treatment: A Special Focus on SARS-CoV-2

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