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 Foster, J. L.
Right arrow Articles by Garcia, J. V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Foster, J. L.
Right arrow Articles by Garcia, J. V.

 Previous Article  |  Next Article 

Journal of Virology, February 2001, p. 1672-1680, Vol. 75, No. 4
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.4.1672-1680.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Genetic and Functional Diversity of Human Immunodeficiency Virus Type 1 Subtype B Nef Primary Isolates

John L. Foster,1 Rene P. Molina,1 Tianci Luo,2 Vivek K. Arora,1 Yaoxing Huang,3 David D. Ho,3 and J. Victor Garcia1,*

Department of Internal Medicine, Division of Infectious Diseases, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 753901; Genetic Therapy, Inc., Gaithersburg, Maryland 208792; and Aaron Diamond AIDS Research Center, Rockefeller University, New York, New York 100163

Received 28 August 2000/Accepted 9 November 2000

We have characterized the functional integrity of seven primary Nef isolates: five from a long-term nonprogressing human immunodeficiency virus (HIV)-infected individual and one each from two patients with AIDS. One of the seven Nefs was defective for CD4 downregulation, two others were defective for PAK-2 activation, and one Nef was defective for PAK-2 activation and major histocompatibility complex (MHC) class I downregulation. Five of the Nefs were tested and found to be functional for the enhancement of virus particle infectivity. The structural basis for each of the functional defects has been analyzed by constructing a consensus nef, followed by mutational analysis of the variant amino acid residues. Mutations A29V and F193I were deleterious to CD4 downregulation and PAK-2 activation, respectively, while S189R rendered Nef defective for both MHC class I downregulation and PAK-2 activation. A search of the literature identified HIVs from five patients with Nefs predominantly mutated at F193 and from one patient with Nefs predominantly mutated at A29. A29 is highly conserved in all HIV subtypes except for subtype E. F193 is conserved in subtype B (and possibly in the closely related subtype D), but none of the other HIV group M subtypes. Our results suggest that functional distinctions may exist between HIV subtypes.

* Corresponding author. Mailing address: Department of Internal Medicine, Division of Infectious Diseases Y9.206, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, TX 75390-9113. Phone: (214) 648-9970. Fax: (214) 648-0231. Email: victor.garcia{at}UTsouthwestern.edu.

Journal of Virology, February 2001, p. 1672-1680, Vol. 75, No. 4
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.4.1672-1680.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Schindler, M., Rajan, D., Specht, A., Ritter, C., Pulkkinen, K., Saksela, K., Kirchhoff, F. (2007). Association of Nef with p21-Activated Kinase 2 Is Dispensable for Efficient Human Immunodeficiency Virus Type 1 Replication and Cytopathicity in Ex Vivo-Infected Human Lymphoid Tissue. J. Virol. 81: 13005-13014 [Abstract] [Full Text]  
  • Priceputu, E., Hanna, Z., Hu, C., Simard, M.-C., Vincent, P., Wildum, S., Schindler, M., Kirchhoff, F., Jolicoeur, P. (2007). Primary Human Immunodeficiency Virus Type 1 Nef Alleles Show Major Differences in Pathogenicity in Transgenic Mice. J. Virol. 81: 4677-4693 [Abstract] [Full Text]  
  • O'Neill, E., Baugh, L. L., Novitsky, V. A., Essex, M. E., Garcia, J. V. (2006). Intra- and intersubtype alternative pak2-activating structural motifs of human immunodeficiency virus type 1 nef.. J. Virol. 80: 8824-8829 [Abstract] [Full Text]  
  • Vincent, P., Priceputu, E., Kay, D., Saksela, K., Jolicoeur, P., Hanna, Z. (2006). Activation of p21-activated Kinase 2 and Its Association with Nef Are Conserved in Murine Cells but Are Not Sufficient to Induce an AIDS-like Disease in CD4C/HIV Transgenic Mice. J. Biol. Chem. 281: 6940-6954 [Abstract] [Full Text]  
  • Agopian, K., Wei, B. L., Garcia, J. V., Gabuzda, D. (2006). A Hydrophobic Binding Surface on the Human Immunodeficiency Virus Type 1 Nef Core Is Critical for Association with p21-Activated Kinase 2. J. Virol. 80: 3050-3061 [Abstract] [Full Text]  
  • O'Neill, E., Kuo, L. S., Krisko, J. F., Tomchick, D. R., Garcia, J. V., Foster, J. L. (2006). Dynamic Evolution of the Human Immunodeficiency Virus Type 1 Pathogenic Factor, Nef. J. Virol. 80: 1311-1320 [Abstract] [Full Text]  
  • Wei, B. L., Arora, V. K., Raney, A., Kuo, L. S., Xiao, G.-H., O'Neill, E., Testa, J. R., Foster, J. L., Garcia, J. V. (2005). Activation of p21-Activated Kinase 2 by Human Immunodeficiency Virus Type 1 Nef Induces Merlin Phosphorylation. J. Virol. 79: 14976-14980 [Abstract] [Full Text]  
  • Raney, A., Kuo, L. S., Baugh, L. L., Foster, J. L., Garcia, J. V. (2005). Reconstitution and Molecular Analysis of an Active Human Immunodeficiency Virus Type 1 Nef/p21-Activated Kinase 2 Complex. J. Virol. 79: 12732-12741 [Abstract] [Full Text]  
  • Milicic, A., Price, D. A., Zimbwa, P., Booth, B. L., Brown, H. L., Easterbrook, P. J., Olsen, K., Robinson, N., Gileadi, U., Sewell, A. K., Cerundolo, V., Phillips, R. E. (2005). CD8+ T Cell Epitope-Flanking Mutations Disrupt Proteasomal Processing of HIV-1 Nef. J. Immunol. 175: 4618-4626 [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»