Journal of Experimental Medicine, Vol 179, 101-113, Copyright © 1994 by Rockefeller University Press

ARTICLES

The human immunodeficiency virus-1 nef gene product: a positive factor for viral infection and replication in primary lymphocytes and macrophages

MD Miller, MT Warmerdam, I Gaston, WC Greene and MB Feinberg
Gladstone Institute of Virology and Immunology, San Francisco, California 94141-9100.

Considerable controversy and uncertainty have surrounded the biological function of the Human Immunodeficiency Virus (HIV)-1 nef gene product. Initial studies suggested that this early, nonstructural viral protein functioned as a negative regulatory factor; thus, it was proposed to play a role in establishing or maintaining viral latency. In contrast, studies in Simian Immunodeficiency Virus (SIV)mac-infected rhesus monkeys have suggested that Nef is not a negative factor but rather plays a central role in promoting high-level viral replication and is required for viral pathogenesis in vivo. We sought to define a tissue culture system that would approximate the in vivo setting for virus infection in order to assess the role of HIV-1 Nef in viral replication. We show that infection of mitogen-activated peripheral blood mononuclear cells (PBMC) with Nef+ HIV results in enhanced replication as evidenced by earlier gag p24 expression when compared with infections performed with nef mutant viruses. Moreover, when unstimulated freshly isolated PBMC are infected with Nef+ and Nef- viruses and then subsequently activated with mitogen, the Nef-induced difference in viral replication kinetics is even more pronounced, with the Nef- viruses requiring much more time in culture for appreciable growth. A positive effect of Nef on viral replication was also observed in primary macrophages infected with a recombinant of YU-2, a patient- derived molecular clone with macrophage tropism. These positive effects of Nef on viral replication are dependent on the initial multiplicity of infection (MOI), in that infections of unstimulated PBMC at low MOI are most dependent upon intact nef for subsequent viral growth. We now provide evidence that the Nef+ HIV is more infectious than Nef- HIV from both a tissue culture infectious dose analysis, and a single-cell HIV infection assay. In the latter case, we demonstrate that infection with equivalent doses of HIV based on virion-associated gag p24 yields five- to sixfold more infected cells if Nef+ viral stocks were used. Furthermore, we find that the differential infectivity is not dependent on CD4 down-regulation as Nef+ virus produced from transfected COS cells lacking CD4 is also more infectious. However, normalization of PBMC infections to equivalent infectivity between that of the Nef+ and Nef- viruses continues to reveal delayed viral replication in the absence of Nef, suggesting that secondary viral spread in PBMC is also enhanced in Nef+ infections. We demonstrate this directly by showing a 13-15-fold increase in infectivity of PBMC-derived Nef+ HIC.(ABSTRACT TRUNCATED AT 400 WORDS)
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• Ikuta, K., Suzuki, S., Horikoshi, H., Mukai, T., Luftig, R. B. (2000). Positive and Negative Aspects of the Human Immunodeficiency Virus Protease: Development of Inhibitors versus Its Role in AIDS Pathogenesis. Microbiol. Mol. Biol. Rev. 64: 725-745 [Abstract] [Full Text]  
• Alessandrini, L., Santarcangelo, A. C., Olivetta, E., Ferrantelli, F., d’Aloja, P., Pugliese, K., Pelosi, E., Chelucci, C., Mattia, G., Peschle, C., Verani, P., Federico, M. (2000). T-tropic human immunodeficiency virus (HIV) type 1 Nef protein enters human monocyte-macrophages and induces resistance to HIV replication: a possible mechanism of HIV T-tropic emergence in AIDS. J. Gen. Virol. 81: 2905-2917 [Abstract] [Full Text]  
• Arora, V. K., Molina, R. P., Foster, J. L., Blakemore, J. L., Chernoff, J., Fredericksen, B. L., Garcia, J. V. (2000). Lentivirus Nef Specifically Activates Pak2. J. Virol. 74: 11081-11087 [Abstract] [Full Text]  
• Albrecht, B., Collins, N. D., Burniston, M. T., Nisbet, J. W., Ratner, L., Green, P. L., Lairmore, M. D. (2000). Human T-Lymphotropic Virus Type 1 Open Reading Frame I p12I Is Required for Efficient Viral Infectivity in Primary Lymphocytes. J. Virol. 74: 9828-9835 [Abstract] [Full Text]  
• Iafrate, A. J., Carl, S., Bronson, S., Stahl-Hennig, C., Swigut, T., Skowronski, J., Kirchhoff, F. (2000). Disrupting Surfaces of Nef Required for Downregulation of CD4 and for Enhancement of Virion Infectivity Attenuates Simian Immunodeficiency Virus Replication In Vivo. J. Virol. 74: 9836-9844 [Abstract] [Full Text]  
• Arthos, J., Rubbert, A., Rabin, R. L., Cicala, C., Machado, E., Wildt, K., Hanbach, M., Steenbeke, T. D., Swofford, R., Farber, J. M., Fauci, A. S. (2000). CCR5 Signal Transduction in Macrophages by Human Immunodeficiency Virus and Simian Immunodeficiency Virus Envelopes. J. Virol. 74: 6418-6424 [Abstract] [Full Text]  
• Swigut, T., Iafrate, A. J., Muench, J., Kirchhoff, F., Skowronski, J. (2000). Simian and Human Immunodeficiency Virus Nef Proteins Use Different Surfaces To Downregulate Class I Major Histocompatibility Complex Antigen Expression. J. Virol. 74: 5691-5701 [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]  
• Le Borgne, S., Février, M., Callebaut, C., Lee, S. P., Rivière, Y. (2000). CD8+-Cell Antiviral Factor Activity Is Not Restricted to Human Immunodeficiency Virus (HIV)-Specific T Cells and Can Block HIV Replication after Initiation of Reverse Transcription. J. Virol. 74: 4456-4464 [Abstract] [Full Text]  
• Carl, S., Iafrate, A. J., Lang, S. M., Stolte, N., Stahl-Hennig, C., Mätz-Rensing, K., Fuchs, D., Skowronski, J., Kirchhoff, F. (2000). Simian Immunodeficiency Virus Containing Mutations in N-Terminal Tyrosine Residues and in the PxxP Motif in Nef Replicates Efficiently in Rhesus Macaques. J. Virol. 74: 4155-4164 [Abstract] [Full Text]  
• Casoli, C., Vicenzi, E., Cimarelli, A., Magnani, G., Ciancianaini, P., Cattaneo, E., Dall'Aglio, P., Poli, G., Bertazzoni, U. (2000). HTLV-II down-regulates HIV-1 replication in IL-2-stimulated primary PBMC of coinfected individuals through expression of MIP-1alpha. Blood 95: 2760-2769 [Abstract] [Full Text]  
• Messmer, D., Ignatius, R., Santisteban, C., Steinman, R. M., Pope, M. (2000). The Decreased Replicative Capacity of Simian Immunodeficiency Virus SIVmac239Delta nef Is Manifest in Cultures of Immature Dendritic Cells and T Cells. J. Virol. 74: 2406-2413 [Abstract] [Full Text]  
• Olivetta, E., Pugliese, K., Bona, R., D'Aloja, P., Ferrantelli, F., Santarcangelo, A. C., Mattia, G., Verani, P., Federico, M. (2000). cis Expression of the F12 Human Immunodeficiency Virus (HIV) Nef Allele Transforms the Highly Productive NL4-3 HIV Type 1 to a Replication-Defective Strain: Involvement of both Env gp41 and CD4 Intracytoplasmic Tails. J. Virol. 74: 483-492 [Abstract] [Full Text]  
• Brown, A., Wang, X., Sawai, E., Cheng-Mayer, C. (1999). Activation of the PAK-Related Kinase by Human Immunodeficiency Virus Type 1 Nef in Primary Human Peripheral Blood Lymphocytes and Macrophages Leads to Phosphorylation of a PIX-p95 Complex. J. Virol. 73: 9899-9907 [Abstract] [Full Text]  
• Akari, H., Uchiyama, T., Fukumori, T., Iida, S., Koyama, A. H., Adachi, A. (1999). Pseudotyping human immunodeficiency virus type 1 by vesicular stomatitis virus G protein does not reduce the cell-dependent requirement of Vif for optimal infectivity: functional difference between Vif and Nef. J. Gen. Virol. 80: 2945-2949 [Abstract] [Full Text]  
• Yoon, K., Kim, S. (1999). Lack of negative influence on the cellular transcription factors NF-{kappa}B and AP-1 by the Nef protein of human immunodeficiency virus type 1. J. Gen. Virol. 80: 2951-2956 [Abstract] [Full Text]  
• Verhasselt, B., Naessens, E., Verhofstede, C., De Smedt, M., Schollen, S., Kerre, T., Vanhecke, D., Plum, J. (1999). Human Immunodeficiency Virus nef Gene Expression Affects Generation and Function of Human T Cells, But Not Dendritic Cells. Blood 94: 2809-2818 [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]  
• Kotov, A., Zhou, J., Flicker, P., Aiken, C. (1999). Association of Nef with the Human Immunodeficiency Virus Type 1 Core. J. Virol. 73: 8824-8830 [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]  
• 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]  
• Learmont, J. C., Geczy, A. F., Mills, J., Ashton, L. J., Raynes-Greenow, C. H., Garsia, R. J., Dyer, W. B., McIntyre, L., Oelrichs, R. B., Rhodes, D. I., Deacon, N. J., Sullivan, J. S., McPhee, D. A., Crowe, S., Solomon, A. E., Chatfield, C., Blasdall, S., Kuipers, H., The Sydney Blood Bank Cohort Research Group, (1999). Immunologic and Virologic Status after 14 to 18 Years of Infection with an Attenuated Strain of HIV-1 -- A Report from the Sydney Blood Bank Cohort. NEJM 340: 1715-1722 [Abstract] [Full Text]  

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