This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow An author's correction has been published
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 Yang, Z.-y.
Right arrow Articles by Nabel, G. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yang, Z.-y.
Right arrow Articles by Nabel, G. J.

 Previous Article  |  Next Article 

Journal of Virology, April 2004, p. 4029-4036, Vol. 78, No. 8
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.8.4029-4036.2004

Selective Modification of Variable Loops Alters Tropism and Enhances Immunogenicity of Human Immunodeficiency Virus Type 1 Envelope

Zhi-yong Yang, Bimal K. Chakrabarti, Ling Xu, Brent Welcher, Wing-pui Kong, Kwanyee Leung, Amos Panet, John R. Mascola, and Gary J. Nabel*

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-3005

Received 22 July 2003/ Accepted 12 January 2004

Although the B clade of human immunodeficiency virus type 1 (HIV-1) envelopes (Env) includes five highly variable regions, each of these domains contains a subset of sequences that remain conserved. The V3 loop has been much studied for its ability to elicit neutralizing antibodies, which are often restricted to a limited number of closely related strains, likely because a large number of antigenic structures are generated from the diverse amino acid sequences in this region. Despite these strain-specific determinants, subregions of V3 are highly conserved, and the effects of different portions of the V3 loop on Env tropism and immunogenicity have not been well delineated. For this report, selective deletions in V3 were introduced by shortening of the stem of the V3 loop. These mutations were explored in combination with deletions of selected V regions. Progressive shortening of the stem of V3 abolished the immunogenicity as well as the functional activity of HIV Env; however, two small deletions on both arms of the V3 stem altered the tropism of the dualtropic 89.6P viral strain so that it infected only CXCR4+ cells. When this smaller deletion was combined with removal of the V1 and V2 loops and used as an immunogen in guinea pigs, the antisera were able to neutralize multiple independent clade B isolates with a higher potency. These findings suggest that highly conserved subregions within V3 may be relevant targets for eliciting neutralizing antibody responses, affecting HIV tropism, and increasing the immunogenicity of AIDS vaccines.

* Corresponding author. Mailing address: Vaccine Research Center, NIAID, National Institutes of Health, Bldg. 40, Room 4502, MSC 3005, 40 Convent Dr., Bethesda, MD 20892-3005. Phone: (301) 496-1852. Fax: (301) 480-0274. E-mail: gnabel{at}mail.nih.gov.

Journal of Virology, April 2004, p. 4029-4036, Vol. 78, No. 8
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.8.4029-4036.2004




This article has been cited by other articles:

  • Agrawal-Gamse, C., Lee, F.-H., Haggarty, B., Jordan, A. P. O., Yi, Y., Lee, B., Collman, R. G., Hoxie, J. A., Doms, R. W., Laakso, M. M. (2009). Adaptive Mutations in a Human Immunodeficiency Virus Type 1 Envelope Protein with a Truncated V3 Loop Restore Function by Improving Interactions with CD4. J. Virol. 83: 11005-11015 [Abstract] [Full Text]  
  • Bontjer, I., Land, A., Eggink, D., Verkade, E., Tuin, K., Baldwin, C., Pollakis, G., Paxton, W. A., Braakman, I., Berkhout, B., Sanders, R. W. (2009). Optimization of Human Immunodeficiency Virus Type 1 Envelope Glycoproteins with V1/V2 Deleted, Using Virus Evolution. J. Virol. 83: 368-383 [Abstract] [Full Text]  
  • Wei, C.-J., Xu, L., Kong, W.-P., Shi, W., Canis, K., Stevens, J., Yang, Z.-Y., Dell, A., Haslam, S. M., Wilson, I. A., Nabel, G. J. (2008). Comparative Efficacy of Neutralizing Antibodies Elicited by Recombinant Hemagglutinin Proteins from Avian H5N1 Influenza Virus. J. Virol. 82: 6200-6208 [Abstract] [Full Text]  
  • Nolan, K. M., Jordan, A. P. O., Hoxie, J. A. (2008). Effects of Partial Deletions within the Human Immunodeficiency Virus Type 1 V3 Loop on Coreceptor Tropism and Sensitivity to Entry Inhibitors. J. Virol. 82: 664-673 [Abstract] [Full Text]  
  • Lin, G., Bertolotti-Ciarlet, A., Haggarty, B., Romano, J., Nolan, K. M., Leslie, G. J., Jordan, A. P.-O., Huang, C.-c., Kwong, P. D., Doms, R. W., Hoxie, J. A. (2007). Replication-Competent Variants of Human Immunodeficiency Virus Type 2 Lacking the V3 Loop Exhibit Resistance to Chemokine Receptor Antagonists. J. Virol. 81: 9956-9966 [Abstract] [Full Text]  
  • Honnen, W. J., Krachmarov, C., Kayman, S. C., Gorny, M. K., Zolla-Pazner, S., Pinter, A. (2007). Type-Specific Epitopes Targeted by Monoclonal Antibodies with Exceptionally Potent Neutralizing Activities for Selected Strains of Human Immunodeficiency Virus Type 1 Map to a Common Region of the V2 Domain of gp120 and Differ Only at Single Positions from the Clade B Consensus Sequence. J. Virol. 81: 1424-1432 [Abstract] [Full Text]  
  • Kong, W.-p., Hood, C., Yang, Z.-y., Wei, C.-J., Xu, L., Garcia-Sastre, A., Tumpey, T. M., Nabel, G. J. (2006). Protective immunity to lethal challenge of the 1918 pandemic influenza virus by vaccination. Proc. Natl. Acad. Sci. USA 103: 15987-15991 [Abstract] [Full Text]  
  • Derby, N. R., Kraft, Z., Kan, E., Crooks, E. T., Barnett, S. W., Srivastava, I. K., Binley, J. M., Stamatatos, L. (2006). Antibody Responses Elicited in Macaques Immunized with Human Immunodeficiency Virus Type 1 (HIV-1) SF162-Derived gp140 Envelope Immunogens: Comparison with Those Elicited during Homologous Simian/Human Immunodeficiency Virus SHIVSF162P4 and Heterologous HIV-1 Infection.. J. Virol. 80: 8745-8762 [Abstract] [Full Text]  
  • Selvarajah, S., Puffer, B., Pantophlet, R., Law, M., Doms, R. W., Burton, D. R. (2005). Comparing Antigenicity and Immunogenicity of Engineered gp120. J. Virol. 79: 12148-12163 [Abstract] [Full Text]  
  • Wu, L., Kong, W.-p., Nabel, G. J. (2005). Enhanced Breadth of CD4 T-Cell Immunity by DNA Prime and Adenovirus Boost Immunization to Human Immunodeficiency Virus Env and Gag Immunogens. J. Virol. 79: 8024-8031 [Abstract] [Full Text]  
  • Santra, S., Seaman, M. S., Xu, L., Barouch, D. H., Lord, C. I., Lifton, M. A., Gorgone, D. A., Beaudry, K. R., Svehla, K., Welcher, B., Chakrabarti, B. K., Huang, Y., Yang, Z.-Y., Mascola, J. R., Nabel, G. J., Letvin, N. L. (2005). Replication-Defective Adenovirus Serotype 5 Vectors Elicit Durable Cellular and Humoral Immune Responses in Nonhuman Primates. J. Virol. 79: 6516-6522 [Abstract] [Full Text]  
  • Mascola, J. R., Sambor, A., Beaudry, K., Santra, S., Welcher, B., Louder, M. K., VanCott, T. C., Huang, Y., Chakrabarti, B. K., Kong, W.-P., Yang, Z.-Y., Xu, L., Montefiori, D. C., Nabel, G. J., Letvin, N. L. (2005). Neutralizing Antibodies Elicited by Immunization of Monkeys with DNA Plasmids and Recombinant Adenoviral Vectors Expressing Human Immunodeficiency Virus Type 1 Proteins. J. Virol. 79: 771-779 [Abstract] [Full Text]  
  • Akahata, W., Yang, Z.-y., Nabel, G. J. (2005). Comparative Immunogenicity of Human Immunodeficiency Virus Particles and Corresponding Polypeptides in a DNA Vaccine. J. Virol. 79: 626-631 [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»