In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 17, No. 8 ( 2021-8-5), p. e1009803-
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.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009803
DOI:
10.1371/journal.ppat.1009803.g001
DOI:
10.1371/journal.ppat.1009803.g002
DOI:
10.1371/journal.ppat.1009803.g003
DOI:
10.1371/journal.ppat.1009803.g004
DOI:
10.1371/journal.ppat.1009803.g005
DOI:
10.1371/journal.ppat.1009803.g006
DOI:
10.1371/journal.ppat.1009803.t001
DOI:
10.1371/journal.ppat.1009803.t002
DOI:
10.1371/journal.ppat.1009803.s001
DOI:
10.1371/journal.ppat.1009803.s002
DOI:
10.1371/journal.ppat.1009803.s003
DOI:
10.1371/journal.ppat.1009803.s004
DOI:
10.1371/journal.ppat.1009803.s005
DOI:
10.1371/journal.ppat.1009803.s006
DOI:
10.1371/journal.ppat.1009803.r001
DOI:
10.1371/journal.ppat.1009803.r002
DOI:
10.1371/journal.ppat.1009803.r003
DOI:
10.1371/journal.ppat.1009803.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2205412-1