Differential cholesterol binding by class II fusion proteins determines membrane fusion properties

M. Umashankar, Claudia Sánchez-San Martín, Maofu Liao, Brigid Reilly, Alice Q. Guo, Gwen Taylor, Margaret Kielian

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

The class II fusion proteins of the alphaviruses and flaviviruses mediate virus infection by driving the fusion of the virus membrane with that of the cell. These fusion proteins are triggered by low pH, and their structures are strikingly similar in both the prefusion dimer and the postfusion homotrimer conformations. Here we have compared cholesterol interactions during membrane fusion by these two groups of viruses. Using cholesteroldepleted insect cells, we showed that fusion and infection by the alphaviruses Semliki Forest virus (SFV) and Sindbis virus were strongly promoted by cholesterol, with similar sterol dependence in laboratory and field isolates and in viruses passaged in tissue culture. The E1 fusion protein from SFV bound cholesterol, as detected by labeling with photocholesterol and by cholesterol extraction studies. In contrast, fusion and infection by numerous strains of the flavivirus dengue virus (DV) and by yellow fever virus 17D were cholesterol independent, and the DV fusion protein did not show significant cholesterol binding. SFV E1 is the first virus fusion protein demonstrated to directly bind cholesterol. Taken together, our results reveal important functional differences conferred by the cholesterol-binding properties of class II fusion proteins.

Original languageEnglish (US)
Pages (from-to)9245-9253
Number of pages9
JournalJournal of Virology
Volume82
Issue number18
DOIs
StatePublished - Sep 2008

Fingerprint

Membrane Fusion Proteins
Cholesterol
cholesterol
Semliki Forest virus
Semliki forest virus
viral fusion proteins
proteins
Viral Fusion Proteins
Alphavirus
Flavivirus
Dengue virus
viruses
Dengue Virus
Alphavirus Infections
Proteins
Yellow fever virus
Sindbis virus
infection
Flaviviridae
Sindbis Virus

ASJC Scopus subject areas

  • Immunology

Cite this

Differential cholesterol binding by class II fusion proteins determines membrane fusion properties. / Umashankar, M.; Sánchez-San Martín, Claudia; Liao, Maofu; Reilly, Brigid; Guo, Alice Q.; Taylor, Gwen; Kielian, Margaret.

In: Journal of Virology, Vol. 82, No. 18, 09.2008, p. 9245-9253.

Research output: Contribution to journalArticle

Umashankar, M. ; Sánchez-San Martín, Claudia ; Liao, Maofu ; Reilly, Brigid ; Guo, Alice Q. ; Taylor, Gwen ; Kielian, Margaret. / Differential cholesterol binding by class II fusion proteins determines membrane fusion properties. In: Journal of Virology. 2008 ; Vol. 82, No. 18. pp. 9245-9253.
@article{8373fd694b4d4b28a9f91bce5e40bb9e,
title = "Differential cholesterol binding by class II fusion proteins determines membrane fusion properties",
abstract = "The class II fusion proteins of the alphaviruses and flaviviruses mediate virus infection by driving the fusion of the virus membrane with that of the cell. These fusion proteins are triggered by low pH, and their structures are strikingly similar in both the prefusion dimer and the postfusion homotrimer conformations. Here we have compared cholesterol interactions during membrane fusion by these two groups of viruses. Using cholesteroldepleted insect cells, we showed that fusion and infection by the alphaviruses Semliki Forest virus (SFV) and Sindbis virus were strongly promoted by cholesterol, with similar sterol dependence in laboratory and field isolates and in viruses passaged in tissue culture. The E1 fusion protein from SFV bound cholesterol, as detected by labeling with photocholesterol and by cholesterol extraction studies. In contrast, fusion and infection by numerous strains of the flavivirus dengue virus (DV) and by yellow fever virus 17D were cholesterol independent, and the DV fusion protein did not show significant cholesterol binding. SFV E1 is the first virus fusion protein demonstrated to directly bind cholesterol. Taken together, our results reveal important functional differences conferred by the cholesterol-binding properties of class II fusion proteins.",
author = "M. Umashankar and {S{\'a}nchez-San Mart{\'i}n}, Claudia and Maofu Liao and Brigid Reilly and Guo, {Alice Q.} and Gwen Taylor and Margaret Kielian",
year = "2008",
month = "9",
doi = "10.1128/JVI.00975-08",
language = "English (US)",
volume = "82",
pages = "9245--9253",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "18",

}

TY - JOUR

T1 - Differential cholesterol binding by class II fusion proteins determines membrane fusion properties

AU - Umashankar, M.

AU - Sánchez-San Martín, Claudia

AU - Liao, Maofu

AU - Reilly, Brigid

AU - Guo, Alice Q.

AU - Taylor, Gwen

AU - Kielian, Margaret

PY - 2008/9

Y1 - 2008/9

N2 - The class II fusion proteins of the alphaviruses and flaviviruses mediate virus infection by driving the fusion of the virus membrane with that of the cell. These fusion proteins are triggered by low pH, and their structures are strikingly similar in both the prefusion dimer and the postfusion homotrimer conformations. Here we have compared cholesterol interactions during membrane fusion by these two groups of viruses. Using cholesteroldepleted insect cells, we showed that fusion and infection by the alphaviruses Semliki Forest virus (SFV) and Sindbis virus were strongly promoted by cholesterol, with similar sterol dependence in laboratory and field isolates and in viruses passaged in tissue culture. The E1 fusion protein from SFV bound cholesterol, as detected by labeling with photocholesterol and by cholesterol extraction studies. In contrast, fusion and infection by numerous strains of the flavivirus dengue virus (DV) and by yellow fever virus 17D were cholesterol independent, and the DV fusion protein did not show significant cholesterol binding. SFV E1 is the first virus fusion protein demonstrated to directly bind cholesterol. Taken together, our results reveal important functional differences conferred by the cholesterol-binding properties of class II fusion proteins.

AB - The class II fusion proteins of the alphaviruses and flaviviruses mediate virus infection by driving the fusion of the virus membrane with that of the cell. These fusion proteins are triggered by low pH, and their structures are strikingly similar in both the prefusion dimer and the postfusion homotrimer conformations. Here we have compared cholesterol interactions during membrane fusion by these two groups of viruses. Using cholesteroldepleted insect cells, we showed that fusion and infection by the alphaviruses Semliki Forest virus (SFV) and Sindbis virus were strongly promoted by cholesterol, with similar sterol dependence in laboratory and field isolates and in viruses passaged in tissue culture. The E1 fusion protein from SFV bound cholesterol, as detected by labeling with photocholesterol and by cholesterol extraction studies. In contrast, fusion and infection by numerous strains of the flavivirus dengue virus (DV) and by yellow fever virus 17D were cholesterol independent, and the DV fusion protein did not show significant cholesterol binding. SFV E1 is the first virus fusion protein demonstrated to directly bind cholesterol. Taken together, our results reveal important functional differences conferred by the cholesterol-binding properties of class II fusion proteins.

UR - http://www.scopus.com/inward/record.url?scp=50949095260&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=50949095260&partnerID=8YFLogxK

U2 - 10.1128/JVI.00975-08

DO - 10.1128/JVI.00975-08

M3 - Article

VL - 82

SP - 9245

EP - 9253

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 18

ER -