Abstract
ABSTRACT Ebola virus contains a single glycoprotein (GP) that is responsible for receptor binding and membrane fusion and is proteolytically cleaved into disulfide-linked GP1 and GP2 subunits. The GP2 subunit possesses a coiled-coil motif, which plays an important role in the oligomerization and fusion activity of other viral GPs. To determine the functional significance of the coiled-coil motif of GP2, we examined the effects of peptides corresponding to the coiled-coil motif of GP2 on the infectivity of a mutant vesicular stomatitis virus (lacking the receptor-binding/fusion protein) pseudotyped with the Ebola virus GP. A peptide corresponding to the C-terminal helix reduced the infectivity of the pseudotyped virus. We next introduced alanine substitutions into hydrophobic residues in the coiled-coil motif to identify residues important for GP function. None of the substitutions affected GP oligomerization, but some mutations, two in the N-terminal helix and all in the C-terminal helix, reduced the ability of GP to confer infectivity to the mutant vesicular stomatitis virus without affecting the transport of GP to the cell surface, its incorporation into virions, and the production of virus particles. These results indicate that the coiled-coil motif of GP2 plays an important role in facilitating the entry of Ebola virus into host cells and that peptides corresponding to this region could act as efficient antiviral agents.
References
55
Referenced
103
10.1016/S1097-2765(00)80458-X
10.1128/jvi.69.5.2745-2750.1995
10.1038/371037a0
10.1093/emboj/17.16.4572
10.1128/jvi.67.5.2747-2755.1993
10.1016/0092-8674(93)90260-W
10.1016/S0092-8674(00)80205-6
10.1073/pnas.95.26.15613
10.1016/S0092-8674(00)81430-0
10.1128/jvi.67.6.3615-3619.1993
10.1128/jvi.68.3.2002-2010.1994
10.1128/jvi.66.8.4748-4756.1992
10.1006/viro.1998.9532
10.1038/nsb0596-465
10.1016/0042-6822(91)90680-A
10.1007/978-3-7091-9300-6_8
10.1006/viro.1994.1147
10.1016/S0092-8674(00)81248-9
10.1073/pnas.89.9.3751
10.1128/JVI.73.10.8907-8912.1999
- Jahrling P. B. Geisbert J. Swearengen J. R. Jaax G. P. Lewis T. Huggins J. W. Schmitdt J. J. LeDuc J. W. Peters C. J. Passive immunization of Ebola virus-infected cynomolgus monkeys with immunoglobulin from hyperimmune horses.Arch. Virol. Suppl. 11 1996 135 140 / Arch. Virol. Suppl. / Passive immunization of Ebola virus-infected cynomolgus monkeys with immunoglobulin from hyperimmune horses by Jahrling P. B. (1996)
10.1038/365113a0
10.1006/viro.1998.9242
10.1038/3293
10.1073/pnas.96.8.4319
10.1006/viro.1993.1561
10.1073/pnas.93.5.2186
10.1128/JVI.73.10.8152-8159.1999
10.1126/science.2237416
10.1073/pnas.95.16.9134
10.1073/pnas.96.6.2662
10.1016/0378-1119(91)90434-D
10.1128/JVI.72.3.2449-2455.1998
- Peters C. J. Sanchez A. Rollin P. E. Ksiazek T. G. Murphy F. A. Filoviridae: Marburg and Ebola viruses Fields virology 3rd ed. Fields B. N. Knipe D. M. Howley P. M. 1996 1161 1176 Lippincott-Raven Publishers Philadelphia Pa
10.1128/jvi.71.3.2041-2049.1997
10.1002/j.1460-2075.1995.tb00239.x
10.1128/jvi.69.10.5995-6004.1995
10.1128/JVI.72.3.1775-1781.1998
10.1016/0168-1702(93)90063-S
10.1073/pnas.93.8.3602
10.1128/JVI.72.8.6442-6447.1998
10.1073/pnas.74.12.5463
10.1016/S0092-8674(00)81655-4
10.1073/pnas.94.26.14764
10.1073/pnas.94.23.12303
10.1016/0014-5793(92)80662-Z
10.1073/pnas.95.10.5762
10.1038/387426a0
10.1016/S1097-2765(00)80159-8
10.1128/JVI.72.12.9676-9682.1998
10.1073/pnas.89.21.10537
10.1073/pnas.91.21.9770
10.1128/JVI.72.4.3155-3160.1998
10.1126/science.279.5353.1034
10.1006/viro.1996.0459
Dates
Type | When |
---|---|
Created | 23 years, 1 month ago (July 27, 2002, 5:58 a.m.) |
Deposited | 3 years, 5 months ago (March 4, 2022, 11:43 p.m.) |
Indexed | 2 months, 1 week ago (June 25, 2025, 6:26 p.m.) |
Issued | 24 years, 10 months ago (Nov. 1, 2000) |
Published | 24 years, 10 months ago (Nov. 1, 2000) |
Published Print | 24 years, 10 months ago (Nov. 1, 2000) |
@article{Watanabe_2000, title={Functional Importance of the Coiled-Coil of the Ebola Virus Glycoprotein}, volume={74}, ISSN={1098-5514}, url={http://dx.doi.org/10.1128/jvi.74.21.10194-10201.2000}, DOI={10.1128/jvi.74.21.10194-10201.2000}, number={21}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Watanabe, Shinji and Takada, Ayato and Watanabe, Tokiko and Ito, Hiroshi and Kida, Hiroshi and Kawaoka, Yoshihiro}, year={2000}, month=nov, pages={10194–10201} }