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Journal of Virology, June 2006, p. 6106-6114, Vol. 80, No. 12
0022-538X/06/$08.00+0     doi:10.1128/JVI.02665-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Murine Leukemia Virus R Peptide Inhibits Influenza Virus Hemagglutinin-Induced Membrane Fusion

Min Li,1,2,{dagger} Zhu-Nan Li,2,{dagger} Qizhi Yao,1,2 Chinglai Yang,2 David A. Steinhauer,2 and Richard W. Compans2*

Molecular Surgeon Research Center, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030,1 Department of Microbiology and Immunology, Emory University, School of Medicine, Atlanta, Georgia 303222

Received 21 December 2005/ Accepted 8 March 2006

The cytoplasmic tail of the murine leukemia virus (MuLV) envelope (Env) protein is known to play an important role in regulating viral fusion activity. Upon removal of the C-terminal 16 amino acids, designated as the R peptide, the fusion activity of the Env protein is activated. To extend our understanding of the inhibitory effect of the R peptide and investigate the specificity of inhibition, we constructed chimeric influenza virus-MuLV hemagglutinin (HA) genes. The influenza virus HA protein is the best-studied membrane fusion model, and we investigated the fusion activities of the chimeric HA proteins. We compared constructs in which the coding sequence for the cytoplasmic tail of the influenza virus HA protein was replaced by that of the wild-type or mutant MuLV Env protein or in which the cytoplasmic tail sequence of the MuLV Env protein was added to the HA cytoplasmic domain. Enzyme-linked immunosorbent assays and Western blot analysis showed that all chimeric HA proteins were effectively expressed on the cell surface and cleaved by trypsin. In BHK21 cells, the wild-type HA protein had a significant ability after trypsin cleavage to induce syncytium formation at pH 5.1; however, neither the chimeric HA protein with the full-length cytoplasmic tail of MuLV Env nor the full-length HA protein followed by the R peptide showed any syncytium formation. When the R peptide was truncated or mutated, the fusion activity was partially recovered in the chimeric HA proteins. A low-pH conformational-change assay showed that similar conformational changes occurred for the wild-type and chimeric HA proteins. All chimeric HA proteins were capable of promoting hemifusion and small fusion pore formation, as shown by a dye redistribution assay. These results indicate that the R peptide of the MuLV Env protein has a sequence-dependent inhibitory effect on influenza virus HA protein-induced membrane fusion and that the inhibitory effect occurs at a late stage in fusion pore enlargement.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322. Phone: (404) 727-5950. Fax: (404) 727-8250. E-mail: compans{at}microbio.emory.edu.

{dagger} M.L. and Z.-N.L. contributed equally to this work.

Journal of Virology, June 2006, p. 6106-6114, Vol. 80, No. 12
0022-538X/06/$08.00+0     doi:10.1128/JVI.02665-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Li, Z.-N., Lee, B.-J., Langley, W. A., Bradley, K. C., Russell, R. J., Steinhauer, D. A. (2008). Length Requirements for Membrane Fusion of Influenza Virus Hemagglutinin Peptide Linkers to Transmembrane or Fusion Peptide Domains. J. Virol. 82: 6337-6348 [Abstract] [Full Text]  
  • Loving, R., Li, K., Wallin, M., Sjoberg, M., Garoff, H. (2008). R-Peptide Cleavage Potentiates Fusion-Controlling Isomerization of the Intersubunit Disulfide in Moloney Murine Leukemia Virus Env. J. Virol. 82: 2594-2597 [Abstract] [Full Text]  


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