Cell entry and release of quasi-enveloped human hepatitis viruses

Das, Anshuman; Rivera-Serrano, Efraín E.; Yin, Xin; Walker, Christopher M.; Feng, Zongdi; Lemon, Stanley M.

doi:10.1038/s41579-023-00889-z

Cited by 29 publications

(16 citation statements)

References 147 publications

(320 reference statements)

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“…HEV is usually transmitted fecal-orally through contaminated food and water 1 . It enters and leaves the human body in its non-enveloped form (nHEV) and circulates in the blood wrapped in a host-derived lipid quasi-envelope (eHEV) acquired during virus budding from cells (reviewed in 6 ). eHEV particles in the blood are protected from neutralizing antibodies, while nHEV particles shed in the faeces facilitate transmission outside the host 7 .…”

Section: Introductionmentioning

confidence: 99%

A high-content RNA-based imaging assay reveals integrin beta 1 as a cofactor for cell entry of non-enveloped hepatitis E virus

Fu,

Engels,

Weihs

et al. 2023

Preprint

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Hepatitis E virus (HEV) is a major cause of acute hepatitis and mainly transmitted faecal-orally. HEV particles in faeces are non-enveloped, while those in the blood possess a cell-derived lipid envelope. Despite being a global health concern, there is limited understanding of the steps in the HEV life cycle, particularly cell entry. A previous study proposed integrin alpha 3 (ITGA3) as a potential host factor for nHEV entry, but the β-integrin partner that co-mediates HEV entry has not been described. To address this knowledge gap and resolve the existing controversies surrounding HEV cell entry, we developed an RNA-FISH-based high-content imaging assay alllowing investigation of the entry pathways of both naked and enveloped HEV particles. Our observations indicate that naked HEV particles interact with the surface receptor integrin beta 1 (ITGB1), which likely facilitates their trafficking through the recycling endosome. In contrast, enveloped HEV particles do not interact with ITGB1 and instead use the classical endocytic pathway via the early endosome. Importantly, both forms of HEV require endosomal acidification and proteolytic cleavage by lysosomal cathepsins, which ultimately results in delivery of the HEV genome to the cytoplasm.

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Section: Introductionmentioning

confidence: 99%

A high-content RNA-based imaging assay reveals integrin beta 1 as a cofactor for cell entry of non-enveloped hepatitis E virus

Fu,

Engels,

Weihs

et al. 2023

Preprint

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“…Hepatitis C virus (HCV) is a positive-stranded RNA virus that causes severe liver disorders and is related to Togaviridae or Flaviviridae. It is a small spherical enveloped virion with an icosahedral capsid (26)(27)(28). Chronic hepatitis B and C viral infections can result in hepatocellular carcinoma (HCC) through mechanisms involving viral integration and chronic inflammation.…”

Section: Hepatitis B and C Virusesmentioning

confidence: 99%

“…Studying these viral integration sites and their impact on host genes is essential for identifying potential therapeutic targets. It is crucial to implement preventative strategies and therapies to eradicate chronic infection of HCV and suppress viral replication for HBV (26,27). state in B cells for the lifetime of the host (29-32).…”

Section: Hepatitis B and C Virusesmentioning

confidence: 99%

Viral oncogenes, viruses, and cancer: a third-generation sequencing perspective on viral integration into the human genome

Ye,

Wang,

et al. 2023

Front. Oncol.

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The link between viruses and cancer has intrigued scientists for decades. Certain viruses have been shown to be vital in the development of various cancers by integrating viral DNA into the host genome and activating viral oncogenes. These viruses include the Human Papillomavirus (HPV), Hepatitis B and C Viruses (HBV and HCV), Epstein-Barr Virus (EBV), and Human T-Cell Leukemia Virus (HTLV-1), which are all linked to the development of a myriad of human cancers. Third-generation sequencing technologies have revolutionized our ability to study viral integration events at unprecedented resolution in recent years. They offer long sequencing capabilities along with the ability to map viral integration sites, assess host gene expression, and track clonal evolution in cancer cells. Recently, researchers have been exploring the application of Oxford Nanopore Technologies (ONT) nanopore sequencing and Pacific BioSciences (PacBio) single-molecule real-time (SMRT) sequencing in cancer research. As viral integration is crucial to the development of cancer via viruses, third-generation sequencing would provide a novel approach to studying the relationship interlinking viral oncogenes, viruses, and cancer. This review article explores the molecular mechanisms underlying viral oncogenesis, the role of viruses in cancer development, and the impact of third-generation sequencing on our understanding of viral integration into the human genome.

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“…Contact with bile removes the membranes, so that "naked" infectious viruses resistant to low pH and temperature changes are excreted in the stool. [1][2][3][4] HAV is transmitted preferentially via the fecal-oral route. Parenteral transmission via blood products is rare.…”

Section: Introductionmentioning

confidence: 99%

“…The HAV is released from the liver into the blood and bile in small vesicles that protect the virions from neutralizing serum antibodies and promote infection of additional hepatocytes. Contact with bile removes the membranes, so that “naked” infectious viruses resistant to low pH and temperature changes are excreted in the stool 1–4 . HAV is transmitted preferentially via the fecal‐oral route.…”

Section: Introductionmentioning

confidence: 99%

Hepatitis A outbreak in a refugee shelter in Kiel, northern Germany

Krumbholz,

Marcic,

Valentin

et al. 2023

Journal of Medical Virology

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In the spring of 2023, three Ukrainian war refugees from a municipal community shelter and a volunteer caregiver at an affiliated daycare center in Kiel, Germany, were diagnosed with infectious jaundice attributable to a single hepatitis A virus (HAV) subgenotype IA strain. Similar HAV sequences have been observed in Germany and other European countries for several years. One refugee and the volunteer required hospitalization. Four children were asymptomatically infected but excreted high levels of HAV ribonucleic acid in the stool. The infections were probably acquired in Germany, but a source could not be determined. The outbreak was contained through vaccination, increased hygiene, and education. The existing HAV vaccination recommendation for refugee shelter staff and volunteers should be consistently implemented.

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Cell entry and release of quasi-enveloped human hepatitis viruses

Cited by 29 publications

References 147 publications

A high-content RNA-based imaging assay reveals integrin beta 1 as a cofactor for cell entry of non-enveloped hepatitis E virus

A high-content RNA-based imaging assay reveals integrin beta 1 as a cofactor for cell entry of non-enveloped hepatitis E virus

Viral oncogenes, viruses, and cancer: a third-generation sequencing perspective on viral integration into the human genome

Hepatitis A outbreak in a refugee shelter in Kiel, northern Germany

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