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Journal of Virology, May 2005, p. 6449-6458, Vol. 79, No. 10
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.10.6449-6458.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Acylation-Mediated Membrane Anchoring of Avian Influenza Virus Hemagglutinin Is Essential for Fusion Pore Formation and Virus Infectivity

Ralf Wagner, Astrid Herwig, Nahid Azzouz, and Hans Dieter Klenk*

Institut für Virologie, Philipps-Universität, 35011 Marburg, Germany

Received 9 August 2004/ Accepted 23 December 2004

Attachment of palmitic acid to cysteine residues is a common modification of viral glycoproteins. The influenza virus hemagglutinin (HA) has three conserved cysteine residues at its C terminus serving as acylation sites. To analyze the structural and functional roles of acylation, we have generated by reverse genetics a series of mutants (Ac1, Ac2, and Ac3) of fowl plague virus (FPV) containing HA in which the acylation sites at positions 551, 559, and 562, respectively, have been abolished. When virus growth in CV1 and MDCK cells was analyzed, similar amounts of virus particles were observed with the mutants and the wild type. Protein patterns and lipid compositions, characterized by high cholesterol and glycolipid contents, were also indistinguishable. However, compared to wild-type virus, Ac2 and Ac3 virions were 10 and almost 1,000 times less infectious, respectively. Fluorescence transfer experiments revealed that loss of acyl chains impeded formation of fusion pores, whereas hemifusion was not affected. When the affinity to detergent-insoluble glycolipid (DIG) domains was analyzed by Triton X-100 treatment of infected cells and virions, solubilization of Ac2 and Ac3 HAs was markedly facilitated. These observations show that acylation of the cytoplasmic tail, while not necessary for targeting to DIG domains, promotes the firm anchoring and retention of FPV HA in these domains. They also indicate that tight DIG association of FPV HA is essential for formation of fusion pores and thus probably for infectivity.

* Corresponding author. Mailing address: Institut für Virologie, Philipps-Universität Marburg, Postfach 2360, 35011 Marburg, Germany. Phone: 49 6421/28-66253. Fax: 49 6421/28-68962. E-mail: klenk{at}staff.uni-marburg.de.

Journal of Virology, May 2005, p. 6449-6458, Vol. 79, No. 10
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.10.6449-6458.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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