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Updated: Aug 14, 2026

Peptide-based Identification of Functional Motifs and their Binding Partners
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Peptide-based Identification of Functional Motifs and their Binding Partners

Published on: July 1, 2013

Extracellular Nef protein regulates productive HIV-1 infection from latency

K Fujinaga1, Q Zhong, T Nakaya

  • 1Section of Serology, Hokkaido University, Kita-ku, Sapporo, Japan.

Journal of Immunology (Baltimore, Md. : 1950)
|December 1, 1995
PubMed

Insights

Soluble HIV-1 Nef protein can activate latent virus in infected cells. A specific Nef peptide (residues 132-147) was identified as responsible for this novel HIV-1 latency activation function.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • The majority of HIV-1 infected cells in asymptomatic carriers are latently or nonproductively infected.
  • A T cell subclone, MOLT-20-2, was isolated exhibiting low-level HIV-1 antigen expression, inducible by stimuli, serving as a model for HIV-1 latency.
  • Previous research indicated the carboxyl-terminal region of extracellular HIV-1 Nef protein is crucial for infected-uninfected T cell interactions and induces cytostasis, suggesting a role in intracellular signaling.

Purpose of the Study:

  • To investigate the role of soluble HIV-1 Nef protein in activating HIV-1 from latency.
  • To identify specific regions of the Nef protein responsible for HIV-1 activation from latency.
  • To confirm the novel function of Nef in activating latent HIV-1 in primary cells and other cell lines.

Main Methods:

  • Stimulation of the latently infected T cell subclone MOLT-20-2 with soluble HIV-1 Nef.
  • Dose-dependent analysis of viral activation.
  • Mapping of stimulatory activity using 14 overlapping synthetic Nef peptides.
  • Confirmation of Nef-dependent activation in primary peripheral blood mononuclear cells (PBMCs) from asymptomatic carriers and other latently infected cell lines (U1, ACH-2).

Main Results:

  • Soluble HIV-1 Nef protein dose-dependently activated HIV-1 from latency in the MOLT-20-2 cell line.
  • A specific peptide, corresponding to amino acid residues 132-147 of Nef, was identified as responsible for this latent HIV-1 activation.
  • This Nef-mediated activation of HIV-1 from latency was confirmed in PBMCs from asymptomatic carriers and the U1 cell line, but not in the ACH-2 cell line.

Conclusions:

  • Soluble HIV-1 Nef protein possesses a novel function in activating latent HIV-1 infection.
  • The carboxyl-terminal region of Nef, specifically residues 132-147, is critical for this activation.
  • Nef plays a significant role in regulating productive HIV-1 infection from latency in vivo, extending its known functions.

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