HIV-1 Nef protein protects infected primary cells against killing by cytotoxic T lymphocytes

@article{Collins1998HIV1NP,
  title={HIV-1 Nef protein protects infected primary cells against killing by cytotoxic T lymphocytes},
  author={Kathleen L. Collins and Benjamin K. Chen and Spyros A. Kalams and Bruce D. Walker and David Baltimore},
  journal={Nature},
  year={1998},
  volume={391},
  pages={397-401}
}
Cytotoxic T lymphocytes (CTLs) lyse virally infected cells that display viral peptide epitopes in association with major histocompatibility complex (MHC) class I molecules on the cell surface. However, despite a strong CTL response directed against viral epitopes, untreated people infected with the human immunodeficiency virus (HIV-1) develop AIDS. To resolve this enigma, we have examined the ability of CTLs to recognize and kill infected primary T lymphocytes. We found that CTLs inefficiently… 
HIV immune evasion disruption of antigen presentation by the HIV Nef protein.
Dendritic cells transfected with the nef genes of HIV‐1 primary isolates specifically activate cytotoxic T lymphocytes from seropositive subjects
TLDR
It is demonstrated that expression and subsequent processing by transfected dendritic cells did not alter the presentation of an immunodominant epitope of Nef to CTL of HIV + subjects, however, mutations in nef gene sequences from primary isolates may abolish this presentation by a mechanism that probably interferes with protein processing.
HIV-1 Vpr does not inhibit CTL-mediated apoptosis of HIV-1 infected cells.
TLDR
Antigen-specific CD8(+) CTL were able to induce apoptosis in HIV-1 infected cells and cells labeled with peptide corresponding to the CTL epitope with equivalent efficiency, demonstrating that neither HIV- 1 Vpr nor any other HIV protein directly inhibits CTL effector functions.
Concanamycin A counteracts HIV-1 Nef to enhance immune clearance of infected primary cells by cytotoxic T lymphocytes
TLDR
The plecomacrolide family of natural products as potent inhibitors of Nef were identified, and concanamycin A restored MHC-I and enhanced the clearance of HIV-infected primary cells by cytotoxic T lymphocytes, indicating the potential for broad therapeutic utility.
HIV's evasion of the cellular immune response
TLDR
Nef is a protein that may promote escape of HIV‐1 from immune surveillance and allow Infected cells to maintain resistance to certain natural killer cells that lyse infected cells expressing low levels of MHC class I antigens.
Nef interference with HIV-1-specific CTL antiviral activity is epitope specific.
TLDR
Examination of the impact of Nef on the antiviral activity of several CTL clones recognizing epitopes from early and late HIV-1 proteins suggests that HLA-C-restricted CTLs may have an under-appreciated antiviral role in the setting of Nf in vivo and suggest a benefit of promoting HLA -C- restricted CTLS for immunotherapy or vaccine development.
Nef-Mediated Resistance of Human Immunodeficiency Virus Type 1 to Antiviral Cytotoxic T Lymphocytes
TLDR
It is concluded that Nef (and not Vpr) contributes to functional HIV-1 immune evasion and that this effect is mediated by diminished antigen presentation to CTL.
Strong Ability of Nef-Specific CD4+ Cytotoxic T Cells To Suppress Human Immunodeficiency Virus Type 1 (HIV-1) Replication in HIV-1-Infected CD4+ T Cells and Macrophages
TLDR
Novel Nef epitope-specific HLA-DRB1*0803-restricted cytotoxic CD4+ T cells are identified and exhibited strong ability to suppress HIV-1 replication in both macrophages and CD4- T cells in vitro.
Milieu of HIV-1 Infection In Vivo Functional Adaptation of Nef to the Immune
TLDR
The functionality of Nef to down-regulate MHC-I in vivo during stable chronic infection is demonstrated, and it is suggested that this function is maintained by the need of HIV-1 to cope with the antiviral CTL response.
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