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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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2021-08-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1009803&type=printable |
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| 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 |
| collection | DOAJ |
| 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 |
| id | doaj-art-494ffbd93696441bb2b9787e8edc5fbf |
| institution | OA Journals |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2021-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-494ffbd93696441bb2b9787e8edc5fbf2025-08-20T02:23:18ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742021-08-01178e100980310.1371/journal.ppat.1009803The degree of polymerization and sulfation patterns in heparan sulfate are critical determinants of cytomegalovirus entry into host cells.Dipanwita MitraMohammad H HasanJohn T BatesMichael A BierdemanDallas R EdererRinkuben C ParmarLauren A FasseroQuntao LiangHong QiuVaibhav TiwariFuming ZhangRobert J LinhardtJoshua S SharpLianchun WangRitesh TandonSeveral 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.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1009803&type=printable |
| spellingShingle | 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. PLoS Pathogens |
| title | 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_short | 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 |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1009803&type=printable |
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