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Journal of Virology, June 2007, p. 6286-6293, Vol. 81, No. 12
0022-538X/07/$08.00+0     doi:10.1128/JVI.00274-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Association of Vaccinia Virus Fusion Regulatory Proteins with the Multicomponent Entry/Fusion Complex{triangledown}

Timothy R. Wagenaar and Bernard Moss*

Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0310, and Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland 20742

Received 8 February 2007/ Accepted 27 March 2007

The proteins encoded by the A56R and K2L genes of vaccinia virus form a heterodimer (A56/K2) and have a fusion regulatory role as deletion or mutation of either causes infected cells to form large syncytia spontaneously. Here, we showed that syncytia formation is dependent on proteins of the recently described entry fusion complex (EFC), which are also required for virus-cell fusion and low-pH-triggered cell-cell fusion. This finding led us to consider that A56/K2 might prevent fusion by direct or indirect interaction with the EFC. To test this hypothesis, we made a panel of recombinant vaccinia viruses that have a tandem affinity purification tag attached to A56, K2, or the A28 EFC protein. Interaction between A56/K2 and the EFC was demonstrated by their copurification from detergent-treated lysates of infected cells and identification by mass spectrometry or Western blotting. In addition, a purified soluble transmembrane-deleted form of A56/K2 was shown to interact with the EFC. Tagged A56 did not interact with the EFC in the absence of K2, nor did tagged K2 interact with the EFC in the absence of A56. The finding that both A56 and K2 are required for efficient binding to the EFC fits well with prior experiments showing that mutation of either A56 or K2 results in spontaneous fusion of infected cells. Because A56 and K2 are located on the surface of infected cells, they are in position to interact with the EFC of released progeny virions and prevent back-fusion and syncytia formation.

* Corresponding author. Mailing address: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 4, Room 229, Bethesda, MD 20892-0310. Phone: (301) 496-9869. Fax: (301) 480-1147. E-mail: bmoss{at}nih.gov

{triangledown} Published ahead of print on 4 April 2007.

Journal of Virology, June 2007, p. 6286-6293, Vol. 81, No. 12
0022-538X/07/$08.00+0     doi:10.1128/JVI.00274-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Wagenaar, T. R., Moss, B. (2009). Expression of the A56 and K2 Proteins Is Sufficient To Inhibit Vaccinia Virus Entry and Cell Fusion. J. Virol. 83: 1546-1554 [Abstract] [Full Text]  
  • Benhnia, M. R.-E.-I., McCausland, M. M., Moyron, J., Laudenslager, J., Granger, S., Rickert, S., Koriazova, L., Kubo, R., Kato, S., Crotty, S. (2009). Vaccinia Virus Extracellular Enveloped Virion Neutralization In Vitro and Protection In Vivo Depend on Complement. J. Virol. 83: 1201-1215 [Abstract] [Full Text]  
  • Nichols, R. J., Stanitsa, E., Unger, B., Traktman, P. (2008). The Vaccinia Virus Gene I2L Encodes a Membrane Protein with an Essential Role in Virion Entry. J. Virol. 82: 10247-10261 [Abstract] [Full Text]  
  • Bisht, H., Weisberg, A. S., Moss, B. (2008). Vaccinia Virus L1 Protein Is Required for Cell Entry and Membrane Fusion. J. Virol. 82: 8687-8694 [Abstract] [Full Text]  
  • Nelson, G. E., Wagenaar, T. R., Moss, B. (2008). A Conserved Sequence within the H2 Subunit of the Vaccinia Virus Entry/Fusion Complex Is Important for Interaction with the A28 Subunit and Infectivity. J. Virol. 82: 6244-6250 [Abstract] [Full Text]  
  • Wagenaar, T. R., Ojeda, S., Moss, B. (2008). Vaccinia Virus A56/K2 Fusion Regulatory Protein Interacts with the A16 and G9 Subunits of the Entry Fusion Complex. J. Virol. 82: 5153-5160 [Abstract] [Full Text]  
  • Girgis, N. M., DeHaven, B. C., Fan, X., Viner, K. M., Shamim, M., Isaacs, S. N. (2008). Cell Surface Expression of the Vaccinia Virus Complement Control Protein Is Mediated by Interaction with the Viral A56 Protein and Protects Infected Cells from Complement Attack. J. Virol. 82: 4205-4214 [Abstract] [Full Text]  
  • Townsley, A. C., Moss, B. (2007). Two Distinct Low-pH Steps Promote Entry of Vaccinia Virus. J. Virol. 81: 8613-8620 [Abstract] [Full Text]  


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