Inhibition of Cellular Factor TM6SF2 Suppresses Secretion Pathways of Hepatitis B, Hepatitis C, and Hepatitis D Viruses
Abstract Chronic viral hepatitis is caused by hepatitis B virus (HBV), hepatitis C virus (HCV), or hepatitis D virus (HDV). Despite different replication strategies, all of these viruses rely on secretion through the host endoplasmic reticulum–Golgi pathway, providing potential host targets for anti...
Gespeichert in:
| Veröffentlicht in: | The Journal of infectious diseases 2024-10, Vol.230 (4), p.970-981 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 981 |
|---|---|
| container_issue | 4 |
| container_start_page | 970 |
| container_title | The Journal of infectious diseases |
| container_volume | 230 |
| creator | Tu, Thomas Ajoyan, Harout Nur Umami, Rifqiyah Veeraraghavan, Vaishnavi Boldbaatar, Delgerbat Najim, Mustafa Ahmed M Khan, Anis Bayoumi, Ali Ho, Vikki Eslam, Mohammed Berg, Thomas Chan, Henry L Y George, Jacob Douglas, Mark W |
| description | Abstract
Chronic viral hepatitis is caused by hepatitis B virus (HBV), hepatitis C virus (HCV), or hepatitis D virus (HDV). Despite different replication strategies, all of these viruses rely on secretion through the host endoplasmic reticulum–Golgi pathway, providing potential host targets for antiviral therapy. Knockdown of transmembrane 6 superfamily member 2 (TM6SF2) in virus cell culture models reduced secretion of infectious HCV virions, HDV virions, and HBV subviral particles. Moreover, in a cohort of people with hepatitis B, a TM6SF2 polymorphism (rs58542926 CT/TT, which causes protein misfolding and reduced TM6SF2 in the liver) correlated with lower concentrations of subviral particles in blood, complementing our previous work showing decreased HCV viral load in people with this polymorphism. In conclusion, the host protein TM6SF2 plays a key role in secretion of HBV, HCV, and HDV, providing the potential for novel pan-viral agents to treat people with chronic viral hepatitis.
Chronic hepatitis viruses HBV, HCV, and HDV all rely on endoplasmic reticulum–Golgi secretion. Knocking down the host gene TM6SF2 in cell culture models reduces secretion of HBV, HCV, and HDV particles, offering the potential for pan-viral therapies to treat chronic hepatitis.
Graphical abstract
Graphical abstract |
| doi_str_mv | 10.1093/infdis/jiae098 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2932435800</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1093/infdis/jiae098</oup_id><sourcerecordid>3133536290</sourcerecordid><originalsourceid>FETCH-LOGICAL-c242t-7b98734ff307fb0bc4dbfc8126462544c0f530be67c18b0da23adac7f76724223</originalsourceid><addsrcrecordid>eNqFkdFP2zAQhy0EGl23Vx6RJV42icDZ59jJI3QrIIGG1MJr5Di2cNUmwU5U9b9funYI8cLT6U7ffbrTj5ATBhcMcrz0tat8vFx4bSHPDsiIpagSKRkekhEA5wnL8vyYfI1xAQACpfpCjjETkKGUI7K-q1986Tvf1LRxdGKXy36pA51q0zWBzh_kbMrprG_bYGO0kc6sCfYf_qi7l7XexO3erW11N1givT5_10zOqa6rd4Nf9NmHfvB8I0dOL6P9vq9j8jT9PZ_cJvd_bu4mV_eJ4YJ3iSrzTKFwDkG5EkojqtKZjHEpJE-FMOBShNJKZVhWQqU56kob5ZRUg4DjmPzYedvQvPY2dsXKRzN8qWvb9LHgOXKBaQYwoGcf0EXTh3q4rkCGmKLk-Za62FEmNDEG64o2-JUOm4JBsY2k2EVS7CMZFk732r5c2eoN_5_BAPzcAU3ffib7C_jKlrw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3133536290</pqid></control><display><type>article</type><title>Inhibition of Cellular Factor TM6SF2 Suppresses Secretion Pathways of Hepatitis B, Hepatitis C, and Hepatitis D Viruses</title><source>MEDLINE</source><source>Oxford University Press Journals All Titles (1996-Current)</source><creator>Tu, Thomas ; Ajoyan, Harout ; Nur Umami, Rifqiyah ; Veeraraghavan, Vaishnavi ; Boldbaatar, Delgerbat ; Najim, Mustafa Ahmed M ; Khan, Anis ; Bayoumi, Ali ; Ho, Vikki ; Eslam, Mohammed ; Berg, Thomas ; Chan, Henry L Y ; George, Jacob ; Douglas, Mark W</creator><creatorcontrib>Tu, Thomas ; Ajoyan, Harout ; Nur Umami, Rifqiyah ; Veeraraghavan, Vaishnavi ; Boldbaatar, Delgerbat ; Najim, Mustafa Ahmed M ; Khan, Anis ; Bayoumi, Ali ; Ho, Vikki ; Eslam, Mohammed ; Berg, Thomas ; Chan, Henry L Y ; George, Jacob ; Douglas, Mark W</creatorcontrib><description>Abstract
Chronic viral hepatitis is caused by hepatitis B virus (HBV), hepatitis C virus (HCV), or hepatitis D virus (HDV). Despite different replication strategies, all of these viruses rely on secretion through the host endoplasmic reticulum–Golgi pathway, providing potential host targets for antiviral therapy. Knockdown of transmembrane 6 superfamily member 2 (TM6SF2) in virus cell culture models reduced secretion of infectious HCV virions, HDV virions, and HBV subviral particles. Moreover, in a cohort of people with hepatitis B, a TM6SF2 polymorphism (rs58542926 CT/TT, which causes protein misfolding and reduced TM6SF2 in the liver) correlated with lower concentrations of subviral particles in blood, complementing our previous work showing decreased HCV viral load in people with this polymorphism. In conclusion, the host protein TM6SF2 plays a key role in secretion of HBV, HCV, and HDV, providing the potential for novel pan-viral agents to treat people with chronic viral hepatitis.
Chronic hepatitis viruses HBV, HCV, and HDV all rely on endoplasmic reticulum–Golgi secretion. Knocking down the host gene TM6SF2 in cell culture models reduces secretion of HBV, HCV, and HDV particles, offering the potential for pan-viral therapies to treat chronic hepatitis.
Graphical abstract
Graphical abstract</description><identifier>ISSN: 0022-1899</identifier><identifier>ISSN: 1537-6613</identifier><identifier>EISSN: 1537-6613</identifier><identifier>DOI: 10.1093/infdis/jiae098</identifier><identifier>PMID: 38408366</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Antiviral agents ; Cell culture ; Endoplasmic reticulum ; Gene polymorphism ; Golgi apparatus ; Hepacivirus - genetics ; Hepacivirus - physiology ; Hepatitis B ; Hepatitis B - metabolism ; Hepatitis B - virology ; Hepatitis B virus - genetics ; Hepatitis B virus - physiology ; Hepatitis C ; Hepatitis Delta Virus - genetics ; Hepatitis Delta Virus - physiology ; Humans ; Male ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Protein folding ; Secretion ; Secretory Pathway ; Virions ; Virus Release ; Virus Replication ; Viruses</subject><ispartof>The Journal of infectious diseases, 2024-10, Vol.230 (4), p.970-981</ispartof><rights>The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. 2024</rights><rights>The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c242t-7b98734ff307fb0bc4dbfc8126462544c0f530be67c18b0da23adac7f76724223</cites><orcidid>0000-0003-4621-3485 ; 0000-0002-0482-4387</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,1584,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38408366$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tu, Thomas</creatorcontrib><creatorcontrib>Ajoyan, Harout</creatorcontrib><creatorcontrib>Nur Umami, Rifqiyah</creatorcontrib><creatorcontrib>Veeraraghavan, Vaishnavi</creatorcontrib><creatorcontrib>Boldbaatar, Delgerbat</creatorcontrib><creatorcontrib>Najim, Mustafa Ahmed M</creatorcontrib><creatorcontrib>Khan, Anis</creatorcontrib><creatorcontrib>Bayoumi, Ali</creatorcontrib><creatorcontrib>Ho, Vikki</creatorcontrib><creatorcontrib>Eslam, Mohammed</creatorcontrib><creatorcontrib>Berg, Thomas</creatorcontrib><creatorcontrib>Chan, Henry L Y</creatorcontrib><creatorcontrib>George, Jacob</creatorcontrib><creatorcontrib>Douglas, Mark W</creatorcontrib><title>Inhibition of Cellular Factor TM6SF2 Suppresses Secretion Pathways of Hepatitis B, Hepatitis C, and Hepatitis D Viruses</title><title>The Journal of infectious diseases</title><addtitle>J Infect Dis</addtitle><description>Abstract
Chronic viral hepatitis is caused by hepatitis B virus (HBV), hepatitis C virus (HCV), or hepatitis D virus (HDV). Despite different replication strategies, all of these viruses rely on secretion through the host endoplasmic reticulum–Golgi pathway, providing potential host targets for antiviral therapy. Knockdown of transmembrane 6 superfamily member 2 (TM6SF2) in virus cell culture models reduced secretion of infectious HCV virions, HDV virions, and HBV subviral particles. Moreover, in a cohort of people with hepatitis B, a TM6SF2 polymorphism (rs58542926 CT/TT, which causes protein misfolding and reduced TM6SF2 in the liver) correlated with lower concentrations of subviral particles in blood, complementing our previous work showing decreased HCV viral load in people with this polymorphism. In conclusion, the host protein TM6SF2 plays a key role in secretion of HBV, HCV, and HDV, providing the potential for novel pan-viral agents to treat people with chronic viral hepatitis.
Chronic hepatitis viruses HBV, HCV, and HDV all rely on endoplasmic reticulum–Golgi secretion. Knocking down the host gene TM6SF2 in cell culture models reduces secretion of HBV, HCV, and HDV particles, offering the potential for pan-viral therapies to treat chronic hepatitis.
Graphical abstract
Graphical abstract</description><subject>Antiviral agents</subject><subject>Cell culture</subject><subject>Endoplasmic reticulum</subject><subject>Gene polymorphism</subject><subject>Golgi apparatus</subject><subject>Hepacivirus - genetics</subject><subject>Hepacivirus - physiology</subject><subject>Hepatitis B</subject><subject>Hepatitis B - metabolism</subject><subject>Hepatitis B - virology</subject><subject>Hepatitis B virus - genetics</subject><subject>Hepatitis B virus - physiology</subject><subject>Hepatitis C</subject><subject>Hepatitis Delta Virus - genetics</subject><subject>Hepatitis Delta Virus - physiology</subject><subject>Humans</subject><subject>Male</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>Protein folding</subject><subject>Secretion</subject><subject>Secretory Pathway</subject><subject>Virions</subject><subject>Virus Release</subject><subject>Virus Replication</subject><subject>Viruses</subject><issn>0022-1899</issn><issn>1537-6613</issn><issn>1537-6613</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkdFP2zAQhy0EGl23Vx6RJV42icDZ59jJI3QrIIGG1MJr5Di2cNUmwU5U9b9funYI8cLT6U7ffbrTj5ATBhcMcrz0tat8vFx4bSHPDsiIpagSKRkekhEA5wnL8vyYfI1xAQACpfpCjjETkKGUI7K-q1986Tvf1LRxdGKXy36pA51q0zWBzh_kbMrprG_bYGO0kc6sCfYf_qi7l7XexO3erW11N1givT5_10zOqa6rd4Nf9NmHfvB8I0dOL6P9vq9j8jT9PZ_cJvd_bu4mV_eJ4YJ3iSrzTKFwDkG5EkojqtKZjHEpJE-FMOBShNJKZVhWQqU56kob5ZRUg4DjmPzYedvQvPY2dsXKRzN8qWvb9LHgOXKBaQYwoGcf0EXTh3q4rkCGmKLk-Za62FEmNDEG64o2-JUOm4JBsY2k2EVS7CMZFk732r5c2eoN_5_BAPzcAU3ffib7C_jKlrw</recordid><startdate>20241016</startdate><enddate>20241016</enddate><creator>Tu, Thomas</creator><creator>Ajoyan, Harout</creator><creator>Nur Umami, Rifqiyah</creator><creator>Veeraraghavan, Vaishnavi</creator><creator>Boldbaatar, Delgerbat</creator><creator>Najim, Mustafa Ahmed M</creator><creator>Khan, Anis</creator><creator>Bayoumi, Ali</creator><creator>Ho, Vikki</creator><creator>Eslam, Mohammed</creator><creator>Berg, Thomas</creator><creator>Chan, Henry L Y</creator><creator>George, Jacob</creator><creator>Douglas, Mark W</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-4621-3485</orcidid><orcidid>https://orcid.org/0000-0002-0482-4387</orcidid></search><sort><creationdate>20241016</creationdate><title>Inhibition of Cellular Factor TM6SF2 Suppresses Secretion Pathways of Hepatitis B, Hepatitis C, and Hepatitis D Viruses</title><author>Tu, Thomas ; Ajoyan, Harout ; Nur Umami, Rifqiyah ; Veeraraghavan, Vaishnavi ; Boldbaatar, Delgerbat ; Najim, Mustafa Ahmed M ; Khan, Anis ; Bayoumi, Ali ; Ho, Vikki ; Eslam, Mohammed ; Berg, Thomas ; Chan, Henry L Y ; George, Jacob ; Douglas, Mark W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c242t-7b98734ff307fb0bc4dbfc8126462544c0f530be67c18b0da23adac7f76724223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Antiviral agents</topic><topic>Cell culture</topic><topic>Endoplasmic reticulum</topic><topic>Gene polymorphism</topic><topic>Golgi apparatus</topic><topic>Hepacivirus - genetics</topic><topic>Hepacivirus - physiology</topic><topic>Hepatitis B</topic><topic>Hepatitis B - metabolism</topic><topic>Hepatitis B - virology</topic><topic>Hepatitis B virus - genetics</topic><topic>Hepatitis B virus - physiology</topic><topic>Hepatitis C</topic><topic>Hepatitis Delta Virus - genetics</topic><topic>Hepatitis Delta Virus - physiology</topic><topic>Humans</topic><topic>Male</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - metabolism</topic><topic>Protein folding</topic><topic>Secretion</topic><topic>Secretory Pathway</topic><topic>Virions</topic><topic>Virus Release</topic><topic>Virus Replication</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tu, Thomas</creatorcontrib><creatorcontrib>Ajoyan, Harout</creatorcontrib><creatorcontrib>Nur Umami, Rifqiyah</creatorcontrib><creatorcontrib>Veeraraghavan, Vaishnavi</creatorcontrib><creatorcontrib>Boldbaatar, Delgerbat</creatorcontrib><creatorcontrib>Najim, Mustafa Ahmed M</creatorcontrib><creatorcontrib>Khan, Anis</creatorcontrib><creatorcontrib>Bayoumi, Ali</creatorcontrib><creatorcontrib>Ho, Vikki</creatorcontrib><creatorcontrib>Eslam, Mohammed</creatorcontrib><creatorcontrib>Berg, Thomas</creatorcontrib><creatorcontrib>Chan, Henry L Y</creatorcontrib><creatorcontrib>George, Jacob</creatorcontrib><creatorcontrib>Douglas, Mark W</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tu, Thomas</au><au>Ajoyan, Harout</au><au>Nur Umami, Rifqiyah</au><au>Veeraraghavan, Vaishnavi</au><au>Boldbaatar, Delgerbat</au><au>Najim, Mustafa Ahmed M</au><au>Khan, Anis</au><au>Bayoumi, Ali</au><au>Ho, Vikki</au><au>Eslam, Mohammed</au><au>Berg, Thomas</au><au>Chan, Henry L Y</au><au>George, Jacob</au><au>Douglas, Mark W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of Cellular Factor TM6SF2 Suppresses Secretion Pathways of Hepatitis B, Hepatitis C, and Hepatitis D Viruses</atitle><jtitle>The Journal of infectious diseases</jtitle><addtitle>J Infect Dis</addtitle><date>2024-10-16</date><risdate>2024</risdate><volume>230</volume><issue>4</issue><spage>970</spage><epage>981</epage><pages>970-981</pages><issn>0022-1899</issn><issn>1537-6613</issn><eissn>1537-6613</eissn><abstract>Abstract
Chronic viral hepatitis is caused by hepatitis B virus (HBV), hepatitis C virus (HCV), or hepatitis D virus (HDV). Despite different replication strategies, all of these viruses rely on secretion through the host endoplasmic reticulum–Golgi pathway, providing potential host targets for antiviral therapy. Knockdown of transmembrane 6 superfamily member 2 (TM6SF2) in virus cell culture models reduced secretion of infectious HCV virions, HDV virions, and HBV subviral particles. Moreover, in a cohort of people with hepatitis B, a TM6SF2 polymorphism (rs58542926 CT/TT, which causes protein misfolding and reduced TM6SF2 in the liver) correlated with lower concentrations of subviral particles in blood, complementing our previous work showing decreased HCV viral load in people with this polymorphism. In conclusion, the host protein TM6SF2 plays a key role in secretion of HBV, HCV, and HDV, providing the potential for novel pan-viral agents to treat people with chronic viral hepatitis.
Chronic hepatitis viruses HBV, HCV, and HDV all rely on endoplasmic reticulum–Golgi secretion. Knocking down the host gene TM6SF2 in cell culture models reduces secretion of HBV, HCV, and HDV particles, offering the potential for pan-viral therapies to treat chronic hepatitis.
Graphical abstract
Graphical abstract</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>38408366</pmid><doi>10.1093/infdis/jiae098</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0003-4621-3485</orcidid><orcidid>https://orcid.org/0000-0002-0482-4387</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-1899 |
| ispartof | The Journal of infectious diseases, 2024-10, Vol.230 (4), p.970-981 |
| issn | 0022-1899 1537-6613 1537-6613 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2932435800 |
| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current) |
| subjects | Antiviral agents Cell culture Endoplasmic reticulum Gene polymorphism Golgi apparatus Hepacivirus - genetics Hepacivirus - physiology Hepatitis B Hepatitis B - metabolism Hepatitis B - virology Hepatitis B virus - genetics Hepatitis B virus - physiology Hepatitis C Hepatitis Delta Virus - genetics Hepatitis Delta Virus - physiology Humans Male Membrane Proteins - genetics Membrane Proteins - metabolism Protein folding Secretion Secretory Pathway Virions Virus Release Virus Replication Viruses |
| title | Inhibition of Cellular Factor TM6SF2 Suppresses Secretion Pathways of Hepatitis B, Hepatitis C, and Hepatitis D Viruses |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-20T06%3A55%3A42IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Inhibition%20of%20Cellular%20Factor%20TM6SF2%20Suppresses%20Secretion%20Pathways%20of%20Hepatitis%20B,%20Hepatitis%20C,%20and%20Hepatitis%20D%20Viruses&rft.jtitle=The%20Journal%20of%20infectious%20diseases&rft.au=Tu,%20Thomas&rft.date=2024-10-16&rft.volume=230&rft.issue=4&rft.spage=970&rft.epage=981&rft.pages=970-981&rft.issn=0022-1899&rft.eissn=1537-6613&rft_id=info:doi/10.1093/infdis/jiae098&rft_dat=%3Cproquest_cross%3E3133536290%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3133536290&rft_id=info:pmid/38408366&rft_oup_id=10.1093/infdis/jiae098&rfr_iscdi=true |