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 Previous Article

Journal of Virology, June 2005, p. 7942-7948, Vol. 79, No. 12
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.12.7942-7948.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Reversible Acid-Induced Inactivation of the Membrane Fusion Protein of Semliki Forest Virus

Barry-Lee Waarts,1 Jolanda M. Smit,1 Onwuchekwa J. C. Aneke,1 Gerald M. McInerney,2 Peter Liljeström,2 Robert Bittman,3 and Jan Wilschut1*

Department of Medical Microbiology, Molecular Virology Section, University Medical Center Groningen, 9713 AV Groningen, The Netherlands,1 Microbiology and Tumor Biology Centre, Karolinska Institute, Stockholm, Sweden,2 Department of Chemistry and Biochemistry, Queens College of the City University of New York, Flushing, New York3

Received 13 August 2004/ Accepted 15 February 2005

Previously, it has been shown that the exposure of Semliki Forest virus (SFV) to a mildly acidic environment induces a rapid and complete loss of the ability of the virus to bind and fuse to target membranes added subsequently. In the present study, incubation of SFV at low pH followed by a specific reneutralization step resulted in a partial reversion of this loss of viral fusion capacity, as assessed in a liposomal model system. Also, the ability of the viral E1 fusion protein to undergo liposome-stimulated trimerization was restored. Furthermore, acid-treated and neutralized SFV largely retained infectivity. Exposure of SFV to low pH induced dissociation of the E1/E2 heterodimer, which was not reversed upon neutralization. It is concluded that the SFV E1 fusion protein, after acid-induced dissociation from E2, rapidly adopts an intermediate, nontrimeric conformation in which it is no longer able to interact with target membrane lipids. Neutralization restores the ability of E1 to interact with membranes. This interaction, however, remains strictly dependent on low pH.

* Corresponding author. Mailing address: Department of Medical Microbiology, Molecular Virology Section, University Medical Center Groningen, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands. Phone: 31-50-3632733. Fax: 31-50-3638171. E-mail: j.c.wilschut{at}med.umcg.nl.

Journal of Virology, June 2005, p. 7942-7948, Vol. 79, No. 12
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.12.7942-7948.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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