HIV/gp120 decreases adult neural progenitor cell proliferation via checkpoint kinase-mediated cell-cycle withdrawal and G1 arrest

Cell Stem Cell. 2007 Aug 16;1(2):230-6. doi: 10.1016/j.stem.2007.07.010.

Abstract

Impaired adult neurogenesis has been observed in several neurodegenerative diseases, including human immunodeficiency virus (HIV-1)-associated dementia (HAD). Here we report that the HIV-envelope glycoprotein gp120, which is associated with HAD pathogenesis, inhibits proliferation of adult neural progenitor cells (aNPCs) in vitro and in vivo in the dentate gyrus of the hippocampus of HIV/gp120-transgenic mice. We demonstrate that HIV/gp120 arrests cell-cycle progression of aNPCs at the G1 phase via a cascade consisting of p38 mitogen-activated protein kinase (MAPK) --> MAPK-activated protein kinase 2 (a cell-cycle checkpoint kinase) --> Cdc25B/C. Our findings define a molecular mechanism that compromises adult neurogenesis in this neurodegenerative disorder.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Dementia Complex / metabolism
  • AIDS Dementia Complex / virology
  • Animals
  • Cell Growth Processes / physiology
  • Female
  • G1 Phase / genetics
  • G1 Phase / physiology
  • HIV Envelope Protein gp120 / genetics
  • HIV Envelope Protein gp120 / physiology*
  • HIV Infections / enzymology
  • HIV Infections / pathology*
  • HIV Infections / virology
  • HIV-1 / physiology*
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • MAP Kinase Signaling System
  • Male
  • Mice
  • Mice, Transgenic
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / virology
  • Neurons / cytology
  • Neurons / enzymology
  • Neurons / physiology*
  • Protein-Serine-Threonine Kinases / metabolism*
  • Rats
  • Stem Cells / physiology*
  • cdc25 Phosphatases / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • HIV Envelope Protein gp120
  • Intracellular Signaling Peptides and Proteins
  • gp120 protein, Human immunodeficiency virus 1
  • MAP-kinase-activated kinase 2
  • Protein-Serine-Threonine Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Cdc25b protein, mouse
  • Cdc25c protein, mouse
  • cdc25 Phosphatases