Disease relevance of nef

• These data show that survival after HIV infection can be determined by the HIV genome and support the importance of nef or the U3 region of the LTR in determining the pathogenicity of HIV-1 [1].
• HIV-1 sequences from either virus isolates or patient peripheral blood mononuclear cells had similar deletions in the nef gene and in the region of overlap of nef and the U3 region of the long terminal repeat (LTR) [1].
• Expression of the nef gene has been shown to be essential to the maintenance of high levels of virus replication and the development of pathogenesis in the animal model of simian immunodeficiency virus (SIV) infection [2].
• The viral regulatory gene, nef, is unique to the human immunodeficiency viruses (HIV) and their related primate lentiviruses [2].
• Thus, in vivo evolution of gp120 Env to CXCR4 use appears to be associated with HIV disease progression in individuals infected with nef-defective viruses [3].

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

• (2006) show that the Nef protein from nonpathogenic strains of simian immunodeficiency virus (SIV) induces the downregulation of host T cell receptor/CD3, whereas Nef from human immunodeficiency virus (HIV-1) does not [5].
• This study demonstrates that nef confers a positive growth advantage to HIV-1 that becomes readily discernable in the primary cell setting of virus induction through T cell activation [2].
• The influence of nef was highly significant for induction of virus replication from a latent state within resting CD4 cells [2].
• The human immunodeficiency virus-1 nef gene product: a positive factor for viral infection and replication in primary lymphocytes and macrophages [6].
• The importance of nef in the induction of human immunodeficiency virus type 1 replication from primary quiescent CD4 lymphocytes [2].

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

• The action of nef was not species restricted; it was able to trans activate in the human monocyte-like cell line Mono Mac 6 [7].
• These data demonstrate that an acute low-level infection of astrocytes rapidly becomes a non-productive infection and this process is assisted by sequences in nef [14].
• Impaired cytotoxic T lymphocyte recognition due to genetic variations in the main immunogenic region of the human immunodeficiency virus 1 NEF protein [15].
• Human immunodeficiency virus type 1 Nef protein is N-terminally myristoylated, a modification reported to be required for the association of Nef with cytoplasmic membranes [16].
• Nef protein expression by wild type pNL4-3 was observed at low levels compared to control HeLa cells at peak virus replication [14].

Associations of nef with chemical compounds

• The effects of nef were multiplicative with those of tat gene product and occurred even in the presence of bacterial lipopolysaccharide, which itself activated LTR-directed transcription [7].
• Multiple cysteines are also found in the nef gene of African green monkey virus, SVIagm, including cysteine at the position analogous to Cys-138 [8].
• In transient expression assays in a T-cell line and a macrophage line, the nef protein of SIVmac1A11 did not significantly suppress or enhance expression of the chloramphenicol acetyltransferase reporter gene linked to the SIVmac long terminal repeat [13].

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].

References