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Journal of Virology, October 2005, p. 12544-12553, Vol. 79, No. 19
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.19.12544-12553.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Characterization of the Infectious Salmon Anemia Virus Fusion Protein

Vidar Aspehaug,^1* Aase B. Mikalsen,² Michael Snow,³ Eirik Biering,^4, and Stéphane Villoing⁴

Department of Biology, University of Bergen, Bergen, Norway,¹ Norwegian School of Veterinary Science, Oslo, Norway,² FRS Marine Laboratory, Aberdeen, United Kingdom,³ Intervet Norbio, Bergen, Norway⁴

Received 24 February 2005/ Accepted 7 July 2005

Infectious salmon anemia virus (ISAV) is an orthomyxovirus causing serious disease in Atlantic salmon (Salmo salar L.). This study presents the characterization of the ISAV 50-kDa glycoprotein encoded by segment 5, here termed the viral membrane fusion protein (F). This is the first description of a separate orthomyxovirus F protein, and to our knowledge, the first pH-dependent separate viral F protein described. The ISAV F protein is synthesized as a precursor protein, F₀, that is proteolytically cleaved to F₁ and F₂, which are held together by disulfide bridges. The cleaved protein is in a metastable, fusion-activated state that can be triggered by low pH, high temperature, or a high concentration of urea. Cell-cell fusion can be initiated by treatment with trypsin and low pH of ISAV-infected cells and of transfected cells expressing F, although the coexpression of ISAV HE significantly improves fusion. Fusion is initiated at pH 5.4 to 5.6, and the fusion process is coincident with the trimerization of the F protein, or most likely a stabilization of the trimer, suggesting that it represents the formation of the fusogenic structure. Exposure to trypsin and a low pH prior to infection inactivated the virus, demonstrating the nonreversibility of this conformational change. Sequence analyses identified a potential coiled coil and a fusion peptide. Size estimates of F₁ and F₂ and the localization of the putative fusion peptide and theoretical trypsin cleavage sites suggest that the proteolytic cleavage site is after residue K²⁷⁶ in the protein sequence.

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* Corresponding author. Mailing address: Department of Biology, University of Bergen, Thormøhlensgate 55, 5020 Bergen, Norway. Phone: 47 913 05 017. Fax: 47 55 58 44 50. E-mail: Vidar.Aspehaug{at}bio.uib.no.

Present address: Institute of Marine Research, Bergen, Norway.

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Journal of Virology, October 2005, p. 12544-12553, Vol. 79, No. 19
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.19.12544-12553.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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