Home LiteratureArticle Details
PMID: 10613821 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

A RhoA-derived peptide inhibits syncytium formation induced by respiratory syncytial virus and parainfluenza virus type 3.

Nature medicine ·Vol. 6 ·No. 1 ·2000-01-00 ·Pages 35-40

Pastey MK, Gower TL, Spearman PW, Crowe JE, Graham BS

Abstract

The fusion glycoproteins of human respiratory syncytial virus (RSV) and human parainfluenza virus type-3 (PIV-3) mediate virus entry and syncytium formation. Interaction between the fusion protein of RSV and RhoA, a small GTPase, facilitates virus-induced syncytium formation. We show here a RhoA-derived peptide inhibits RSV and syncytium formation induced by RSV and PIV-3, both in vitro by inhibition of cell-to-cell fusion and in vivo by reduction of peak titer by 2 log10 in RSV-infected mice. These findings indicate that the interaction between these two paramyxovirus fusion proteins and RhoA is an important target for new antiviral strategies.

MeSH Terms
Amino Acid Sequence Animals Cell Fusion Cells, Cultured Enzyme-Linked Immunosorbent Assay Giant Cells/drug effects,physiology,virology Humans Mice Mice, Inbred BALB C Molecular Sequence Data Parainfluenza Virus 3, Human/drug effects,genetics,physiology Peptide Fragments/chemistry,pharmacology Respiratory Syncytial Virus Infections/physiopathology Respiratory Syncytial Virus, Human/drug effects,genetics,physiology Vaccinia virus/physiology rhoA GTP-Binding Protein/chemistry,physiology
Chemicals
Peptide Fragments rhoA GTP-Binding Protein
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Pastey M K
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Gower T L
Spearman P W
Crowe J E
Graham B S
References (26)
26 references, click to expand
  1. Analysis of bovine respiratory syncytial virus envelope glycoproteins in cell fusion.
    J Gen Virol. 1997 Aug;78 ( Pt 8):1885-9 PMID: 9266983
  2. Primary respiratory syncytial virus infection in mice.
    J Med Virol. 1988 Oct;26(2):153-62 PMID: 3183639
  3. Heparin-dependent attachment of respiratory syncytial virus (RSV) to host cells.
    Arch Virol. 1997;142(6):1247-54 PMID: 9229012
  4. RhoA interacts with the fusion glycoprotein of respiratory syncytial virus and facilitates virus-induced syncytium formation.
    J Virol. 1999 Sep;73(9):7262-70 PMID: 10438814
  5. Analysis of the murine leukemia virus R peptide: delineation of the molecular determinants which are important for its fusion inhibition activity.
    J Virol. 1997 Nov;71(11):8490-6 PMID: 9343206
  6. Demonstration that glycoprotein G is the attachment protein of respiratory syncytial virus.
    J Gen Virol. 1987 Sep;68 ( Pt 9):2521-4 PMID: 3655746
  7. Effects of fusion temperature on the lateral mobility of Sendai virus glycoproteins in erythrocyte membranes and on cell fusion indicate that glycoprotein mobilization is required for cell fusion.
    Biochemistry. 1988 Jul 26;27(15):5654-61 PMID: 2846047
  8. Immunization of cotton rats with the fusion (F) and large (G) glycoproteins of respiratory syncytial virus (RSV) protects against RSV challenge without potentiating RSV disease.
    Vaccine. 1989 Dec;7(6):533-40 PMID: 2692334
  9. Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry.
    Nat Med. 1998 Nov;4(11):1302-7 PMID: 9809555
  10. Analysis of respiratory syncytial virus F, G, and SH proteins in cell fusion.
    Virology. 1994 May 1;200(2):801-5 PMID: 8178462
  11. Identification of a linear heparin binding domain for human respiratory syncytial virus attachment glycoprotein G.
    J Virol. 1999 Aug;73(8):6610-7 PMID: 10400758
  12. Post-translational processing and oligomerization of the fusion glycoprotein of human respiratory syncytial virus.
    J Gen Virol. 1991 Dec;72 ( Pt 12):3095-101 PMID: 1765771
  13. Peptides from conserved regions of paramyxovirus fusion (F) proteins are potent inhibitors of viral fusion.
    Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):2186-91 PMID: 8700906
  14. HIV-induced syncytia of a T cell line form single giant pseudopods and are motile.
    J Cell Sci. 1993 Nov;106 ( Pt 3):941-53 PMID: 8308076
  15. Heptad repeat sequences are located adjacent to hydrophobic regions in several types of virus fusion glycoproteins.
    J Gen Virol. 1990 Dec;71 ( Pt 12):3075-80 PMID: 2177097
  16. A synthetic peptide corresponding to a conserved heptad repeat domain is a potent inhibitor of Sendai virus-cell fusion: an emerging similarity with functional domains of other viruses.
    EMBO J. 1995 Nov 15;14(22):5524-31 PMID: 8521809
  17. Virus-cell and cell-cell fusion.
    Annu Rev Cell Dev Biol. 1996;12:627-61 PMID: 8970739
  18. Natural history of parainfluenza virus infection in childhood.
    J Pediatr. 1982 Aug;101(2):180-7 PMID: 6284899
  19. Studies with cross-linking reagents on the oligomeric form of the paramyxovirus fusion protein.
    Virology. 1994 Feb 15;199(1):160-8 PMID: 8116239
  20. The small GTPase Rho: cellular functions and signal transduction.
    J Biochem. 1996 Aug;120(2):215-28 PMID: 8889802
  21. Peptides corresponding to a predictive alpha-helical domain of human immunodeficiency virus type 1 gp41 are potent inhibitors of virus infection.
    Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9770-4 PMID: 7937889
  22. Peptides corresponding to the heptad repeat sequence of human parainfluenza virus fusion protein are potent inhibitors of virus infection.
    Virology. 1996 Sep 1;223(1):103-12 PMID: 8806544
  23. Membrane fusion promoted by increasing surface densities of the paramyxovirus F and HN proteins: comparison of fusion reactions mediated by simian virus 5 F, human parainfluenza virus type 3 F, and influenza virus HA.
    J Virol. 1998 Oct;72(10):7745-53 PMID: 9733810
  24. Isolation of paramyxovirus glycoproteins. Association of both hemagglutinating and neuraminidase activities with the larger SV5 glycoprotein.
    Virology. 1972 Dec;50(3):640-52 PMID: 4118317
  25. Respiratory syncytial virus (RSV) SH and G proteins are not essential for viral replication in vitro: clinical evaluation and molecular characterization of a cold-passaged, attenuated RSV subgroup B mutant.
    Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13961-6 PMID: 9391135
  26. Cholesterol enhances mouse hepatitis virus-mediated cell fusion.
    Virology. 1988 Apr;163(2):276-83 PMID: 2833007
Article Info
Journal
Nature medicine
Abbr.
Nat Med
ISSN
1078-8956
DOI
10.1038/71503
Published
2000-01-00
Pages
35-40
Language
English
Region
United States
NLM ID
9502015
PMCID
PMC7095870
Subset
IM
Grants
NIDDK NIH HHS · P30 DK020593 · United States
NCI NIH HHS · P30 CA068485 · United States
NCI NIH HHS · CA68485 · United States
NIAID NIH HHS · R01-AI-33933 · United States
NIDDK NIH HHS · DK20593 · United States
NIAID NIH HHS · R01 AI033933 · United States
External Links
PubMed source DOI: 10.1038/71503 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2