This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ye, L.
Right arrow Articles by Yang, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ye, L.
Right arrow Articles by Yang, C.

 Previous Article  |  Next Article 

Journal of Virology, December 2004, p. 13409-13419, Vol. 78, No. 24
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.24.13409-13419.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Surface Stability and Immunogenicity of the Human Immunodeficiency Virus Envelope Glycoprotein: Role of the Cytoplasmic Domain

Ling Ye,1,{dagger} Zhigao Bu,2,{dagger} Andrei Vzorov,1 Dahnide Taylor,1 Richard W. Compans,1 and Chinglai Yang1*

Department of Microbiology & Immunology and Vaccine Center, Emory University School of Medicine, Atlanta, Georgia,1 National Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Harbin, People's Republic of China2

Received 12 April 2004/ Accepted 12 August 2004

The effects of two functional domains, the membrane-proximal YXX{Phi} motif and the membrane-distal inhibitory sequence in the long cytoplasmic tail of the human immunodeficiency virus type 1 (HIV-1) envelope protein (Env), on immunogenicity of the envelope protein were investigated. Genes with codons optimized for mammalian expression were synthesized for the HIV 89.6 Env and a truncated Env with 50 amino acids in the cytoplasmic domain to delete the membrane distal inhibitory sequence for surface expression. Additional genes were generated in which the tyrosine residue in the YXX{Phi} motif was changed into a serine. Pulse-chase radioactive labeling and immunoprecipitation studies indicated that both domains can mediate endocytosis of the HIV Env, and removal of both domains is required to enhance HIV Env protein surface stability. Analysis of immune responses induced by DNA immunization of mice showed that the DNA construct for the mutant Env exhibiting enhanced surface stability induced significantly higher levels of antibody responses against the HIV Env protein. Our results suggest that the HIV Env cytoplasmic domain may play important roles in virus infection and pathogenesis by modulating its immunogenicity.

* Corresponding author. Mailing address: Department of Microbiology and Immunology and Vaccine Center, Emory University School of Medicine, 1510 Clifton Rd., Room 3033, Rollins Research Center, Atlanta, GA 30322. Phone: (404) 712-9607. Fax: (404) 727-3659. E-mail: chyang{at}emory.edu.

{dagger} L.Y. and Z.B. contributed equally to this work.

Journal of Virology, December 2004, p. 13409-13419, Vol. 78, No. 24
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.24.13409-13419.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Zhu, Q., Zarnitsyn, V. G., Ye, L., Wen, Z., Gao, Y., Pan, L., Skountzou, I., Gill, H. S., Prausnitz, M. R., Yang, C., Compans, R. W. (2009). Immunization by vaccine-coated microneedle arrays protects against lethal influenza virus challenge. Proc. Natl. Acad. Sci. USA 106: 7968-7973 [Abstract] [Full Text]  
  • Kassa, A., Finzi, A., Pancera, M., Courter, J. R., Smith, A. B. III, Sodroski, J. (2009). Identification of a Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Variant Resistant to Cold Inactivation. J. Virol. 83: 4476-4488 [Abstract] [Full Text]  
  • Zhu, Q., Yang, H., Chen, W., Cao, W., Zhong, G., Jiao, P., Deng, G., Yu, K., Yang, C., Bu, Z., Kawaoka, Y., Chen, H. (2008). A Naturally Occurring Deletion in Its NS Gene Contributes to the Attenuation of an H5N1 Swine Influenza Virus in Chickens. J. Virol. 82: 220-228 [Abstract] [Full Text]  
  • Wang, B.-Z., Liu, W., Kang, S.-M., Alam, M., Huang, C., Ye, L., Sun, Y., Li, Y., Kothe, D. L., Pushko, P., Dokland, T., Haynes, B. F., Smith, G., Hahn, B. H., Compans, R. W. (2007). Incorporation of High Levels of Chimeric Human Immunodeficiency Virus Envelope Glycoproteins into Virus-Like Particles. J. Virol. 81: 10869-10878 [Abstract] [Full Text]  
  • Waheed, A. A., Ablan, S. D., Mankowski, M. K., Cummins, J. E., Ptak, R. G., Schaffner, C. P., Freed, E. O. (2006). Inhibition of HIV-1 Replication by Amphotericin B Methyl Ester: SELECTION FOR RESISTANT VARIANTS. J. Biol. Chem. 281: 28699-28711 [Abstract] [Full Text]  
  • Beddows, S., Schulke, N., Kirschner, M., Barnes, K., Franti, M., Michael, E., Ketas, T., Sanders, R. W., Maddon, P. J., Olson, W. C., Moore, J. P. (2005). Evaluating the Immunogenicity of a Disulfide-Stabilized, Cleaved, Trimeric Form of the Envelope Glycoprotein Complex of Human Immunodeficiency Virus Type 1. J. Virol. 79: 8812-8827 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»