This Article Full Text (PDF) A correction has been published Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shugars, D C Articles by Swanstrom, R Search for Related Content PubMed PubMed Citation Articles by Shugars, D C Articles by Swanstrom, R

Analysis of human immunodeficiency virus type 1 nef gene sequences present in vivo.

Department of Microbiology and Immunology, UNC School of Dentistry, Chapel Hill.

ABSTRACT

The nef genes of the human immunodeficiency viruses type 1 and 2 (HIV-1 and HIV-2) and the related simian immunodeficiency viruses (SIVs) encode a protein (Nef) whose role in virus replication and cytopathicity remains uncertain. As an attempt to elucidate the function of nef, we characterized the nucleotide and corresponding protein sequences of naturally occurring nef genes obtained from several HIV-1-infected individuals. A consensus Nef sequence was derived and used to identify several features that were highly conserved among the Nef sequences. These features included a nearly invariant myristylation signal, regions of sequence polymorphism and variable duplication, a region with an acidic charge, a (Pxx)4 repeat sequence, and a potential protein kinase C phosphorylation site. Clustering of premature stop codons at position 124 was noted in 6 of the 54 Nef sequences. Further analysis revealed four stretches of residues that were highly conserved not only among the patient-derived HIV-1 Nef sequences, but also among the Nef sequences of HIV-2 and the SIVs, suggesting that Nef proteins expressed by these retroviruses are functionally equivalent. The "Nef-defining" sequences were used to evaluate the sequence alignments of known proteins reported to share sequence similarity with Nef sequences and to conduct additional computer-based searches for similar protein sequences. A gene encoding the consensus Nef sequence was also generated. This gene encodes a full-length Nef protein that should be a valuable tool in further studies of Nef function.

This article has been cited by other articles:

• Goepfert, P. A., Lumm, W., Farmer, P., Matthews, P., Prendergast, A., Carlson, J. M., Derdeyn, C. A., Tang, J., Kaslow, R. A., Bansal, A., Yusim, K., Heckerman, D., Mulenga, J., Allen, S., Goulder, P. J.R., Hunter, E. (2008). Transmission of HIV-1 Gag immune escape mutations is associated with reduced viral load in linked recipients. J. Exp. Med. 205: 1009-1017 [Abstract] [Full Text]  
• Lindwasser, O. W., Smith, W. J., Chaudhuri, R., Yang, P., Hurley, J. H., Bonifacino, J. S. (2008). A Diacidic Motif in Human Immunodeficiency Virus Type 1 Nef Is a Novel Determinant of Binding to AP-2. J. Virol. 82: 1166-1174 [Abstract] [Full Text]  
• Hiyoshi, M., Suzu, S., Yoshidomi, Y., Hassan, R., Harada, H., Sakashita, N., Akari, H., Motoyoshi, K., Okada, S. (2008). Interaction between Hck and HIV-1 Nef negatively regulates cell surface expression of M-CSF receptor. Blood 111: 243-250 [Abstract] [Full Text]  
• Noviello, C. M., Pond, S. L. K., Lewis, M. J., Richman, D. D., Pillai, S. K., Yang, O. O., Little, S. J., Smith, D. M., Guatelli, J. C. (2007). Maintenance of Nef-Mediated Modulation of Major Histocompatibility Complex Class I and CD4 after Sexual Transmission of Human Immunodeficiency Virus Type 1. J. Virol. 81: 4776-4786 [Abstract] [Full Text]  
• Chaudhuri, R., Lindwasser, O. W., Smith, W. J., Hurley, J. H., Bonifacino, J. S. (2007). Downregulation of CD4 by Human Immunodeficiency Virus Type 1 Nef Is Dependent on Clathrin and Involves Direct Interaction of Nef with the AP2 Clathrin Adaptor. J. Virol. 81: 3877-3890 [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]  
• Kumar, M., Mitra, D. (2005). Heat Shock Protein 40 Is Necessary for Human Immunodeficiency Virus-1 Nef-mediated Enhancement of Viral Gene Expression and Replication. J. Biol. Chem. 280: 40041-40050 [Abstract] [Full Text]  
• Suzu, S., Harada, H., Matsumoto, T., Okada, S. (2005). HIV-1 Nef interferes with M-CSF receptor signaling through Hck activation and inhibits M-CSF bioactivities. Blood 105: 3230-3237 [Abstract] [Full Text]  
• Williams, M., Roeth, J. F., Kasper, M. R., Filzen, T. M., Collins, K. L. (2005). Human Immunodeficiency Virus Type 1 Nef Domains Required for Disruption of Major Histocompatibility Complex Class I Trafficking Are Also Necessary for Coprecipitation of Nef with HLA-A2. J. Virol. 79: 632-636 [Abstract] [Full Text]  
• Roeth, J. F., Williams, M., Kasper, M. R., Filzen, T. M., Collins, K. L. (2004). HIV-1 Nef disrupts MHC-I trafficking by recruiting AP-1 to the MHC-I cytoplasmic tail. J. Cell Biol. 167: 903-913 [Abstract] [Full Text]  
• Kasper, M. R., Collins, K. L. (2003). Nef-Mediated Disruption of HLA-A2 Transport to the Cell Surface in T Cells. J. Virol. 77: 3041-3049 [Abstract] [Full Text]  
• Hiipakka, M., Saksela, K. (2002). Capacity of simian immunodeficiency virus strain mac Nef for high-affinity Src homology 3 (SH3) binding revealed by ligand-tailored SH3 domains. J. Gen. Virol. 83: 3147-3152 [Abstract] [Full Text]  
• Williams, M., Roeth, J. F., Kasper, M. R., Fleis, R. I., Przybycin, C. G., Collins, K. L. (2002). Direct Binding of Human Immunodeficiency Virus Type 1 Nef to the Major Histocompatibility Complex Class I (MHC-I) Cytoplasmic Tail Disrupts MHC-I Trafficking. J. Virol. 76: 12173-12184 [Abstract] [Full Text]  
• Husain, M., Gusella, G. L., Klotman, M. E., Gelman, I. H., Ross, M. D., Schwartz, E. J., Cara, A., Klotman, P. E. (2002). HIV-1 Nef Induces Proliferation and Anchorage-Independent Growth in Podocytes. J. Am. Soc. Nephrol. 13: 1806-1815 [Abstract] [Full Text]  
• Hayashi, N., Matsubara, M., Jinbo, Y., Titani, K., Izumi, Y., Matsushima, N. (2002). Nef of HIV-1 interacts directly with calcium-bound calmodulin. Protein Sci. 11: 529-537 [Abstract] [Full Text]  
• Canki, M., Thai, J. N. F., Chao, W., Ghorpade, A., Potash, M. J., Volsky, D. J. (2001). Highly Productive Infection with Pseudotyped Human Immunodeficiency Virus Type 1 (HIV-1) Indicates No Intracellular Restrictions to HIV-1 Replication in Primary Human Astrocytes. J. Virol. 75: 7925-7933 [Abstract] [Full Text]  
• Janvier, K., Craig, H., Le Gall, S., Benarous, R., Guatelli, J., Schwartz, O., Benichou, S. (2001). Nef-Induced CD4 Downregulation: a Diacidic Sequence in Human Immunodeficiency Virus Type 1 Nef Does Not Function as a Protein Sorting Motif through Direct Binding to {beta}-COP. J. Virol. 75: 3971-3976 [Abstract] [Full Text]  
• Foster, J. L., Molina, R. P., Luo, T., Arora, V. K., Huang, Y., Ho, D. D., Garcia, J. V. (2001). Genetic and Functional Diversity of Human Immunodeficiency Virus Type 1 Subtype B Nef Primary Isolates. J. Virol. 75: 1672-1680 [Abstract] [Full Text]  
• Walk, S. F., Alexander, M., Maier, B., Hammarskjold, M.-L., Rekosh, D. M., Ravichandran, K. S. (2001). Design and Use of an Inducibly Activated Human Immunodeficiency Virus Type 1 Nef To Study Immune Modulation. J. Virol. 75: 834-843 [Abstract] [Full Text]  
• Rhodes, D. I., Ashton, L., Solomon, A., Carr, A., Cooper, D., Kaldor, J., Deacon, N. (2000). Characterization of Three nef-Defective Human Immunodeficiency Virus Type 1 Strains Associated with Long-Term Nonprogression. J. Virol. 74: 10581-10588 [Abstract] [Full Text]  
• Liu, L. X., Heveker, N., Fackler, O. T., Arold, S., Le Gall, S., Janvier, K., Peterlin, B. M., Dumas, C., Schwartz, O., Benichou, S., Benarous, R. (2000). Mutation of a Conserved Residue (D123) Required for Oligomerization of Human Immunodeficiency Virus Type 1 Nef Protein Abolishes Interaction with Human Thioesterase and Results in Impairment of Nef Biological Functions. J. Virol. 74: 5310-5319 [Abstract] [Full Text]  
• Collette, Y., Arold, S., Picard, C., Janvier, K., Benichou, S., Benarous, R., Olive, D., Dumas, C. (2000). HIV-2 and SIV Nef Proteins Target Different Src Family SH3 Domains than Does HIV-1 Nef because of a Triple Amino Acid Substitution. J. Biol. Chem. 275: 4171-4176 [Abstract] [Full Text]  
• Kirchhoff, F., Munch, J., Carl, S., Stolte, N., Matz-Rensing, K., Fuchs, D., Ten Haaft, P., Heeney, J. L., Swigut, T., Skowronski, J., Stahl-Hennig, C. (1999). The Human Immunodeficiency Virus Type 1 nef Gene Can to a Large Extent Replace Simian Immunodeficiency Virus nef In Vivo. J. Virol. 73: 8371-8383 [Abstract] [Full Text]  
• Bresnahan, P. A., Yonemoto, W., Greene, W. C. (1999). Cutting Edge: SIV Nef Protein Utilizes Both Leucine- and Tyrosine-Based Protein Sorting Pathways for Down-Regulation of CD4. J. Immunol. 163: 2977-2981 [Abstract] [Full Text]  
• Kalams, S. A., Buchbinder, S. P., Rosenberg, E. S., Billingsley, J. M., Colbert, D. S., Jones, N. G., Shea, A. K., Trocha, A. K., Walker, B. D. (1999). Association between Virus-Specific Cytotoxic T-Lymphocyte and Helper Responses in Human Immunodeficiency Virus Type 1 Infection. J. Virol. 73: 6715-6720 [Abstract] [Full Text]  
• Schrager, J. A., Marsh, J. W. (1999). HIV-1 Nef increases T cell activation in a stimulus-dependent manner. Proc. Natl. Acad. Sci. USA 96: 8167-8172 [Abstract] [Full Text]  
• Kirchhoff, F., Easterbrook, P. J., Douglas, N., Troop, M., Greenough, T. C., Weber, J., Carl, S., Sullivan, J. L., Daniels, R. S. (1999). Sequence Variations in Human Immunodeficiency Virus Type 1 Nef Are Associated with Different Stages of Disease. J. Virol. 73: 5497-5508 [Abstract] [Full Text]  
• Alexander, L., Du, Z., Howe, A. Y. M., Czajak, S., Desrosiers, R. C. (1999). Induction of AIDS in Rhesus Monkeys by a Recombinant Simian Immunodeficiency Virus Expressing nef of Human Immunodeficiency Virus Type 1. J. Virol. 73: 5814-5825 [Abstract] [Full Text]  
• Howe, A. Y. M., Jung, J. U., Desrosiers, R. C. (1998). Zeta Chain of the T-Cell Receptor Interacts with nef of Simian Immunodeficiency Virus and Human Immunodeficiency Virus Type 2. J. Virol. 72: 9827-9834 [Abstract] [Full Text]  
• Craig, H. M., Pandori, M. W., Guatelli, J. C. (1998). Interaction of HIV-1 Nef with the cellular dileucine-based sorting pathway is required for CD4 down-regulation and optimal viral infectivity. Proc. Natl. Acad. Sci. USA 95: 11229-11234 [Abstract] [Full Text]  
• Aldrovandi, G. M., Gao, L., Bristol, G., Zack, J. A. (1998). Regions of Human Immunodeficiency Virus Type 1 nef Required for Function In Vivo. J. Virol. 72: 7032-7039 [Abstract] [Full Text]  
• Khan, I. H., Sawai, E. T., Antonio, E., Weber, C. J., Mandell, C. P., Montbriand, P., Luciw, P. A. (1998). Role of the SH3-Ligand Domain of Simian Immunodeficiency Virus Nef in Interaction with Nef-Associated Kinase and Simian AIDS in Rhesus Macaques. J. Virol. 72: 5820-5830 [Abstract] [Full Text]  
• Yamanaka, M. K., Yilma, T. (1998). Altered Plaque Formation by Recombinant Vaccinia Virus Expressing Simian Immunodeficiency Virus Nef. J. Virol. 72: 5291-5295 [Abstract] [Full Text]  
• Salvi, R., Garbuglia, A. R., Di Caro, A., Pulciani, S., Montella, F., Benedetto, A. (1998). Grossly Defective nef Gene Sequences in a Human Immunodeficiency Virus Type 1-Seropositive Long-Term Nonprogressor. J. Virol. 72: 3646-3657 [Abstract] [Full Text]  
• Wei, Q., Fultz, P. N. (1998). Extensive Diversification of Human Immunodeficiency Virus Type 1 Subtype B Strains during Dual Infection of a Chimpanzee That Progressed to AIDS. J. Virol. 72: 3005-3017 [Abstract] [Full Text]  
• Coates, K., Cooke, S. J., Mann, D. A., Harris, M. P. G. (1997). Protein Kinase C-mediated Phosphorylation of HIV-I Nef in Human Cell Lines. J. Biol. Chem. 272: 12289-12294 [Abstract] [Full Text]  
• Sanfridson, A., Hester, S., Doyle, C. (1997). Nef proteins encoded by human and simian immunodeficiency viruses induce the accumulation of endosomes and lysosomes in human T cells. Proc. Natl. Acad. Sci. USA 94: 873-878 [Abstract] [Full Text]  
• Collette, Y., Dutartre, H., Benziane, A., Ramos-Morales, F., Benarous, R., Harris, M., Olive, D. (1996). Physical and Functional Interaction of Nef with Lck. J. Biol. Chem. 271: 6333-6341 [Abstract] [Full Text]  
• Deacon, N. J., Tsykin, A., Solomon, A., Smith, K., Ludford-Menting, M., Ellett, A., Hooker, D. J., McPhee, D. A., Greenway, A. L., Chatfield, C., Lawson, V. A., Crowe, S., Maerz, A., Sonza, S., Learmont, J., Sullivan, J. S., Cunningham, A., Dwyer, D., Dowton, D., Mills, J. (1995). Genomic Structure of an Attenuated Quasi Species of HIV-1 from a Blood Transfusion Donor and Recipients. Science 270: 988-991 [Abstract]  
• Kirchhoff, F., Greenough, T. C., Brettler, D. B., Sullivan, J. L., Desrosiers, R. C. (1995). Absence of Intact nef Sequences in a Long-Term Survivor with Nonprogressive HIV-1 Infection. NEJM 332: 228-232 [Full Text]  
• Liu, X., Schrager, J. A., Lange, G. D., Marsh, J. W. (2001). HIV Nef-mediated Cellular Phenotypes Are Differentially Expressed as a Function of Intracellular NEF Concentrations. J. Biol. Chem. 276: 32763-32770 [Abstract] [Full Text]  
• Briggs, S. D., Scholtz, B., Jacque, J.-M., Swingler, S., Stevenson, M., Smithgall, T. E. (2001). HIV-1 Nef Promotes Survival of Myeloid Cells by a Stat3-dependent Pathway. J. Biol. Chem. 276: 25605-25611 [Abstract] [Full Text]  
• Manninen, A., Herma Renkema, G., Saksela, K. (2000). Synergistic Activation of NFAT by HIV-1 Nef and the Ras/MAPK Pathway. J. Biol. Chem. 275: 16513-16517 [Abstract] [Full Text]