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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,{dagger} 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.

{dagger} 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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