The degree of polymerization and sulfation patterns in heparan sulfate are critical determinants of cytomegalovirus entry into host cells.

Several enveloped viruses, including herpesviruses attach to host cells by initially interacting with cell surface heparan sulfate (HS) proteoglycans followed by specific coreceptor engagement which culminates in virus-host membrane fusion and virus entry. Interfering with HS-herpesvirus interaction...

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Autores principales:	Dipanwita Mitra, Mohammad H Hasan, John T Bates, Michael A Bierdeman, Dallas R Ederer, Rinkuben C Parmar, Lauren A Fassero, Quntao Liang, Hong Qiu, Vaibhav Tiwari, Fuming Zhang, Robert J Linhardt, Joshua S Sharp, Lianchun Wang, Ritesh Tandon
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/494ffbd93696441bb2b9787e8edc5fbf
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spelling	oai:doaj.org-article:494ffbd93696441bb2b9787e8edc5fbf2021-12-02T20:00:25ZThe degree of polymerization and sulfation patterns in heparan sulfate are critical determinants of cytomegalovirus entry into host cells.1553-73661553-737410.1371/journal.ppat.1009803https://doaj.org/article/494ffbd93696441bb2b9787e8edc5fbf2021-08-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009803https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Several enveloped viruses, including herpesviruses attach to host cells by initially interacting with cell surface heparan sulfate (HS) proteoglycans followed by specific coreceptor engagement which culminates in virus-host membrane fusion and virus entry. Interfering with HS-herpesvirus interactions has long been known to result in significant reduction in virus infectivity indicating that HS play important roles in initiating virus entry. In this study, we provide a series of evidence to prove that specific sulfations as well as the degree of polymerization (dp) of HS govern human cytomegalovirus (CMV) binding and infection. First, purified CMV extracellular virions preferentially bind to sulfated longer chain HS on a glycoarray compared to a variety of unsulfated glycosaminoglycans including unsulfated shorter chain HS. Second, the fraction of glycosaminoglycans (GAG) displaying higher dp and sulfation has a larger impact on CMV titers compared to other fractions. Third, cell lines deficient in specific glucosaminyl sulfotransferases produce significantly reduced CMV titers compared to wild-type cells and virus entry is compromised in these mutant cells. Finally, purified glycoprotein B shows strong binding to heparin, and desulfated heparin analogs compete poorly with heparin for gB binding. Taken together, these results highlight the significance of HS chain length and sulfation patterns in CMV attachment and infectivity.Dipanwita MitraMohammad H HasanJohn T BatesMichael A BierdemanDallas R EdererRinkuben C ParmarLauren A FasseroQuntao LiangHong QiuVaibhav TiwariFuming ZhangRobert J LinhardtJoshua S SharpLianchun WangRitesh TandonPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 8, p e1009803 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Dipanwita Mitra Mohammad H Hasan John T Bates Michael A Bierdeman Dallas R Ederer Rinkuben C Parmar Lauren A Fassero Quntao Liang Hong Qiu Vaibhav Tiwari Fuming Zhang Robert J Linhardt Joshua S Sharp Lianchun Wang Ritesh Tandon The degree of polymerization and sulfation patterns in heparan sulfate are critical determinants of cytomegalovirus entry into host cells.
description	Several enveloped viruses, including herpesviruses attach to host cells by initially interacting with cell surface heparan sulfate (HS) proteoglycans followed by specific coreceptor engagement which culminates in virus-host membrane fusion and virus entry. Interfering with HS-herpesvirus interactions has long been known to result in significant reduction in virus infectivity indicating that HS play important roles in initiating virus entry. In this study, we provide a series of evidence to prove that specific sulfations as well as the degree of polymerization (dp) of HS govern human cytomegalovirus (CMV) binding and infection. First, purified CMV extracellular virions preferentially bind to sulfated longer chain HS on a glycoarray compared to a variety of unsulfated glycosaminoglycans including unsulfated shorter chain HS. Second, the fraction of glycosaminoglycans (GAG) displaying higher dp and sulfation has a larger impact on CMV titers compared to other fractions. Third, cell lines deficient in specific glucosaminyl sulfotransferases produce significantly reduced CMV titers compared to wild-type cells and virus entry is compromised in these mutant cells. Finally, purified glycoprotein B shows strong binding to heparin, and desulfated heparin analogs compete poorly with heparin for gB binding. Taken together, these results highlight the significance of HS chain length and sulfation patterns in CMV attachment and infectivity.
format	article
author	Dipanwita Mitra Mohammad H Hasan John T Bates Michael A Bierdeman Dallas R Ederer Rinkuben C Parmar Lauren A Fassero Quntao Liang Hong Qiu Vaibhav Tiwari Fuming Zhang Robert J Linhardt Joshua S Sharp Lianchun Wang Ritesh Tandon
author_facet	Dipanwita Mitra Mohammad H Hasan John T Bates Michael A Bierdeman Dallas R Ederer Rinkuben C Parmar Lauren A Fassero Quntao Liang Hong Qiu Vaibhav Tiwari Fuming Zhang Robert J Linhardt Joshua S Sharp Lianchun Wang Ritesh Tandon
author_sort	Dipanwita Mitra
title	The degree of polymerization and sulfation patterns in heparan sulfate are critical determinants of cytomegalovirus entry into host cells.
title_short	The degree of polymerization and sulfation patterns in heparan sulfate are critical determinants of cytomegalovirus entry into host cells.
title_full	The degree of polymerization and sulfation patterns in heparan sulfate are critical determinants of cytomegalovirus entry into host cells.
title_fullStr	The degree of polymerization and sulfation patterns in heparan sulfate are critical determinants of cytomegalovirus entry into host cells.
title_full_unstemmed	The degree of polymerization and sulfation patterns in heparan sulfate are critical determinants of cytomegalovirus entry into host cells.
title_sort	degree of polymerization and sulfation patterns in heparan sulfate are critical determinants of cytomegalovirus entry into host cells.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/494ffbd93696441bb2b9787e8edc5fbf
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The degree of polymerization and sulfation patterns in heparan sulfate are critical determinants of cytomegalovirus entry into host cells.

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