A role for 3-O-sulfated heparan sulfate in promoting human cytomegalovirus infection in human iris cells.

Abstract:

:Human cytomegalovirus (HCMV) has emerged as a clinically opportunistic pathogen that targets multiple types of ocular cells and tissues, including the iris region of the uveal tract during anterior uveitis. In this report, we used primary cultures of human iris stroma (HIS) cells derived from human eye donors to investigate HCMV entry. The following lines of evidence suggested the role of 3-O-sulfated heparan sulfate (3-OS HS) during HCMV-mediated entry and cell-to-cell fusion in HIS cells. First, 3-O-sulfotransferase-3 (3-OST-3) expression in HIS cells promoted HCMV internalization, while pretreatment of HIS cells with heparinase enzyme or with anti-3-OS HS (G2) peptide significantly reduced the HCMV-mediated formation of plaques/foci. Second, coculture of the HCMV-infected HIS cells with CHO-K1 cells expressing 3-OS HS significantly enhanced cell fusion. Finally, a similar trend of enhanced fusion was observed with cells expressing HCMV glycoproteins (gB, gO, and gH-gL) cocultured with 3-OS HS cells. Taken together, these results highlight the role of 3-OS HS during HCMV plaque formation and cell-to-cell fusion and identify a novel target for future therapeutic interventions.

journal_name

J Virol

journal_title

Journal of virology

authors

Baldwin J,Maus E,Zanotti B,Volin MV,Tandon R,Shukla D,Tiwari V

doi

10.1128/JVI.00109-15

subject

Has Abstract

pub_date

2015-05-01 00:00:00

pages

5185-92

issue

9

eissn

0022-538X

issn

1098-5514

pii

JVI.00109-15

journal_volume

89

pub_type

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