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The hiv-1 nef protein inhibits extracellular signal-regulated kinase-dependent DNA synthesis in a human astrocytic cell line

Academic Article
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Overview

authors

  • Romero, I. A.
  • Teixeira, A.
  • Strosberg, Donny
  • Cazaubon, S.
  • Couraud, P. O.

publication date

  • February 1998

journal

  • Journal of Neurochemistry  Journal

abstract

  • The role of nonproductive infection of astrocytes by human immunodeficiency virus type 1 (HIV-1), characterized by the overexpression of nef, in brain disease progression is largely unknown. We investigated the consequences of stable expression of nef from the HIV-1 strain LAI in the human astrocytic cell line U373. DNA synthesis induced by endothelin-1 (ET-1) was largely decreased by nef. Stable expression of nef did not affect the ET-1-induced tyrosine phosphorylation of focal adhesion kinase, an adhesion-dependent pathway known to participate in DNA synthesis in astrocytes. Conversely, the activation of extracellular signal-regulated kinase (ERK) by ET-1 was largely inhibited in cells stably or transiently expressing nef. A similar inhibitory action of nef on ERK activation was observed after direct stimulation of G proteins. Furthermore, the inhibitory action of nef did not require protein kinase C (PKC) and affected mainly the PKC-independent pathway of ERK activation. Following chemokine receptor CXCR4-mediated infection of U373 cells stably expressing CXCR4 with the T-tropic HIV-1 strain m7-NDK, ET-1-induced activation of ERK was also inhibited. Altogether, these results indicate that intracellular signaling pathways associated with the growth factor activity of ET-1 are impaired in nef-expressing and HIV-1-infected astrocytes, suggesting that infection of astrocytes may play a significant role in the neuropathogenesis of HIV-1 encephalopathy.

subject areas

  • Astrocytes
  • Astrocytoma
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Cell Adhesion Molecules
  • Cell Line
  • DNA Replication
  • Endothelin-1
  • Enzyme Activation
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Gene Products, nef
  • HIV-1
  • Humans
  • Mitogen-Activated Protein Kinase 1
  • Protein-Tyrosine Kinases
  • Receptors, CCR4
  • Receptors, Chemokine
  • Recombinant Proteins
  • Transfection
  • nef Gene Products, Human Immunodeficiency Virus
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Research

keywords

  • DNA synthesis
  • astrocytes
  • endothelin
  • extracellular signal-regulated kinase
  • human immunodeficiency virus
  • nef
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Identity

International Standard Serial Number (ISSN)

  • 0022-3042

PubMed ID

  • 9453574
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Additional Document Info

start page

  • 778

end page

  • 785

volume

  • 70

issue

  • 2

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