The degree of polymerization and sulfation patterns in heparan sulfate are critical determinants of cytomegalovirus entry into host cells
Loading...
Authors
Mitra, Dipanwita
Hasan, Mohammad H.
Bates, John T.
Bierdeman, Michael A.
Ederer, Dallas R.
Parmar, Rinkuben C.
Fassero, Lauren A.
Liang, Quntao
Qiu, Hong
Tiwari, Vaibhav
Issue Date
2021-08-01
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
Abstract
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.
Description
PLOS Pathogens, 17 (8), e1009803
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Full Citation
The degree of polymerization and sulfation patterns in heparan sulfate are critical determinants of cytomegalovirus entry into host cells, M. H. Hasan, D. Mitra, J. T. Bates, M. A. Bierdeman, R. C. Parmar, L. A. Fassero, Q. Liang, H. Qiu, V. Tiwari, F. Zhang, R. J. Linhardt, J. S. Sharp, L. Wang, R. Tandon, PLOS Pathogens, 17 (8), e1009803, 2021.
Publisher
Public Library of Science (PLoS)
Terms of Use
Journal
Volume
Issue
PubMed ID
DOI
ISSN
15537374
15537366
15537366