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Journal of Virology, February 2004, p. 1403-1410, Vol. 78, No. 3
0022-538X/04/$08.00+0 DOI: 10.1128/JVI.78.3.1403-1410.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
The Mature Avian Leukosis Virus Subgroup A Envelope Glycoprotein Is Metastable, and Refolding Induced by the Synergistic Effects of Receptor Binding and Low pH Is Coupled to Infection
Jason G. Smith,1 Walther Mothes,1,
Stephen C. Blacklow,2 and James M. Cunningham1*
Department of Medicine,1
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 021152
Received 17 June 2003/
Accepted 18 October 2003
The spring-loaded model stipulates that influenza virus infection is coupled to the transition of the virus hemagglutinin (HA) from a metastable conformation to a highly stable conformation at low pH. The properties of retrovirus envelope glycoproteins indicate that infection is coupled to an analogous conformational change. As a test of this hypothesis, the requirements for avian leukosis virus A (ALV-A) infection were examined. These studies indicate that, like HA, the conformation of the mature ALV-A envelope glycoprotein is metastable and that infection is linked to refolding at low pH. However, unlike HA, low-pH activation is only observed after priming by receptor. Therefore, ALV-A infection is dependent on the synergistic effects of receptor binding and low pH, suggesting that receptor binding superimposes an additional constraint on activation of ALV-A fusion that proceeds by a mechanism comparable to that of influenza virus.
* Corresponding author. Mailing address: Room 1030, Thorn Building, Brigham and Women's Hospital, 20 Shattuck St., Boston, MA 02115. Phone: (617) 732-5852. Fax: (617) 738-5575. E-mail: cunningham{at}rascal.med.harvard.edu.
Present address: Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06510.
Journal of Virology, February 2004, p. 1403-1410, Vol. 78, No. 3
0022-538X/04/$08.00+0 DOI: 10.1128/JVI.78.3.1403-1410.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
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Copyright © 2004 by the American Society for Microbiology. All rights reserved.