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Gene Review

nef  -  nef protein

Simian-Human immunodeficiency virus

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Disease relevance of nef


Psychiatry related information on nef

  • One HIV-1 clone, BRVA, obtained by coculture from the brain of an adult AIDS patient with progressive dementia, was previously shown to contain a duplicated region in nef [4].

High impact information on nef


Chemical compound and disease context of nef

  • By contrast to previous reports indicating a negative role for nef in HIV transcription, cotransfection of RAW264 cells with a nef expression plasmid trans activated the HIV-1 LTR driving either a chloramphenicol acetyltransferase or a luciferase reporter gene [7].
  • When this sequence was compared to the sequence database for AIDS and human retroviruses at Los Alamos, New Mexico, several isolates from other asymptomatic individuals were also found to encode nef genes with a cysteine at position 138 [8].
  • Genomic Diversity in the Regulatory nef Gene Sequences in Indian Isolates of HIV Type 1: Emergence of a Distinct Subclade and Predicted Implications [9].
  • We report that in CD4(+) human lymphoblastoid cell lines transfected with the nef cDNA obtained from three different HIV-1 strains, expression of the Nef protein enhances and accelerates the response to four unrelated apoptotic agents (staurosporine, anisomycin, camptothecin, and etoposide) but not to an anti-Fas agonist Ab [10].
  • Interaction with simian Hck tyrosine kinase reveals convergent evolution of the Nef protein from simian and human immunodeficiency viruses despite differential molecular surface usage [11].

Biological context of nef

  • With this cell model, NL4-3 virus clones with open and mutated nef reading frames were compared for replication competence [2].
  • In contrast to this in vivo model, the use of standard T cell culture systems to study nef function in vitro has produced a spectrum of contradictory results, and has failed to demonstrate a significant positive influence of nef on viral life cycle [2].
  • However, these promising efficacy results are overshadowed by safety problems, such as reversion of the vaccine strain to a pathogenic virus encoding full-length nef or residual virulence of multiply deleted vaccine strains [12].
  • The presence of a nef expression cassette in a neomycin phosphotransferase gene expression plasmid greatly reduced the number of G418-resistant colonies generated in stable transfection of RAW264 cells, and many of the colonies that were formed exhibited very slow growth [7].
  • In this report, we demonstrate that SIVmac1A11 contains a full open reading frame for nef which specifies a 37-kDa protein [13].

Anatomical context of nef


Associations of nef with chemical compounds


Analytical, diagnostic and therapeutic context of nef

  • Thus, lentivirus-mediated shRNA expression targeting the U3-overlapping region of HIV nef represents a feasible approach to genetic vaccine therapy for HIV-1 [17].
  • However, coculture strongly selects against the broad spectrum of nef quasispecies found in tissue [4].
  • PCR analysis of circulating provirus indicates that the nef gene evolved over time in pJ5 virus-infected macaques, whereas late in infection in pC8 virus-infected macaques the nef gene remained invariant in sequence [18].
  • On the basis of our results, we performed epitope mapping of the Nef protein and identified a novel epitope [19].


  1. Genomic structure of an attenuated quasi species of HIV-1 from a blood transfusion donor and recipients. Deacon, N.J., Tsykin, A., Solomon, A., Smith, K., Ludford-Menting, M., Hooker, D.J., McPhee, D.A., Greenway, A.L., Ellett, A., Chatfield, C., Lawson, V.A., Crowe, S., Maerz, A., Sonza, S., Learmont, J., Sullivan, J.S., Cunningham, A., Dwyer, D., Dowton, D., Mills, J. Science (1995) [Pubmed]
  2. The importance of nef in the induction of human immunodeficiency virus type 1 replication from primary quiescent CD4 lymphocytes. Spina, C.A., Kwoh, T.J., Chowers, M.Y., Guatelli, J.C., Richman, D.D. J. Exp. Med. (1994) [Pubmed]
  3. Nef Alleles from Human Immunodeficiency Virus Type 1-Infected Long-Term-Nonprogressor Hemophiliacs with or without Late Disease Progression Are Defective in Enhancing Virus Replication and CD4 Down-Regulation. Crotti, A., Neri, F., Corti, D., Ghezzi, S., Heltai, S., Baur, A., Poli, G., Santagostino, E., Vicenzi, E. J. Virol. (2006) [Pubmed]
  4. Human immunodeficiency virus type 1 nef quasispecies in pathological tissue. Blumberg, B.M., Epstein, L.G., Saito, Y., Chen, D., Sharer, L.R., Anand, R. J. Virol. (1992) [Pubmed]
  5. HIV pathogenesis: Nef loses control. Foster, J.L., Garcia, J.V. Cell (2006) [Pubmed]
  6. The human immunodeficiency virus-1 nef gene product: a positive factor for viral infection and replication in primary lymphocytes and macrophages. Miller, M.D., Warmerdam, M.T., Gaston, I., Greene, W.C., Feinberg, M.B. J. Exp. Med. (1994) [Pubmed]
  7. Effects of the tat and nef gene products of human immunodeficiency virus type 1 (HIV-1) on transcription controlled by the HIV-1 long terminal repeat and on cell growth in macrophages. Murphy, K.M., Sweet, M.J., Ross, I.L., Hume, D.A. J. Virol. (1993) [Pubmed]
  8. The nef gene from a long-term HIV type 1 nonprogressor. Premkumar, D.R., Ma, X.Z., Maitra, R.K., Chakrabarti, B.K., Salkowitz, J., Yen-Lieberman, B., Hirsch, M.S., Kestler, H.W. AIDS Res. Hum. Retroviruses (1996) [Pubmed]
  9. Genomic Diversity in the Regulatory nef Gene Sequences in Indian Isolates of HIV Type 1: Emergence of a Distinct Subclade and Predicted Implications. Kumar, M., Jain, S.K., Pasha, S.T., Chattopadhaya, D., Lal, S., Rai, A. AIDS Res. Hum. Retroviruses (2006) [Pubmed]
  10. Apoptosis enhancement by the HIV-1 Nef protein. Rasola, A., Gramaglia, D., Boccaccio, C., Comoglio, P.M. J. Immunol. (2001) [Pubmed]
  11. Interaction with simian Hck tyrosine kinase reveals convergent evolution of the Nef protein from simian and human immunodeficiency viruses despite differential molecular surface usage. Picard, C., Greenway, A., Holloway, G., Olive, D., Collette, Y. Virology (2002) [Pubmed]
  12. Live attenuated AIDS viruses as vaccines: promise or peril? Ruprecht, R.M. Immunol. Rev. (1999) [Pubmed]
  13. The nef gene of simian immunodeficiency virus SIVmac1A11. Unger, R.E., Marthas, M.L., Pratt-Lowe, E., Padrid, P.A., Luciw, P.A. J. Virol. (1992) [Pubmed]
  14. Restricted HIV-1 infection of human astrocytes: potential role of nef in the regulation of virus replication. Gorry, P., Purcell, D., Howard, J., McPhee, D. J. Neurovirol. (1998) [Pubmed]
  15. Impaired cytotoxic T lymphocyte recognition due to genetic variations in the main immunogenic region of the human immunodeficiency virus 1 NEF protein. Couillin, I., Culmann-Penciolelli, B., Gomard, E., Choppin, J., Levy, J.P., Guillet, J.G., Saragosti, S. J. Exp. Med. (1994) [Pubmed]
  16. Role of myristoylation and N-terminal basic residues in membrane association of the human immunodeficiency virus type 1 Nef protein. Bentham, M., Mazaleyrat, S., Harris, M. J. Gen. Virol. (2006) [Pubmed]
  17. Lentivirus vectors expressing short hairpin RNAs against the U3-overlapping region of HIV nef inhibit HIV replication and infectivity in primary macrophages. Yamamoto, T., Miyoshi, H., Yamamoto, N., Yamamoto, N., Inoue, J., Tsunetsugu-Yokota, Y. Blood (2006) [Pubmed]
  18. Molecular and biological characterization of simian immunodeficiency virus macaque strain 32H proviral clones containing nef size variants. Rud, E.W., Cranage, M., Yon, J., Quirk, J., Ogilvie, L., Cook, N., Webster, S., Dennis, M., Clarke, B.E. J. Gen. Virol. (1994) [Pubmed]
  19. Expression of a novel Nef epitope on the surface of HIV type 1-infected cells. Yamada, T., Iwamoto, A. AIDS Res. Hum. Retroviruses (1999) [Pubmed]
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