PUBLICATION

HIV-1 Nef Interferes with Host Cell Motility by Deregulation of Cofilin

Authors
Stolp, B., Reichman-Fried, M., Abraham, L., Pan, X., Giese, S.I., Hannemann, S., Goulimari, P., Raz, E., Grosse, R., and Fackler, O.T.
ID
ZDB-PUB-090819-6
Date
2009
Source
Cell Host & Microbe   6(2): 174-186 (Journal)
Registered Authors
Raz, Erez, Reichman-Fried, Michal
Keywords
MICROBIO, CELLBIO, CELLIMMUNO
MeSH Terms
  • Actin Depolymerizing Factors/metabolism*
  • Cell Line
  • Cell Movement*
  • Cells, Cultured
  • Fibroblasts/virology
  • HIV-1/pathogenicity*
  • Humans
  • T-Lymphocytes/virology
  • Virulence Factors/physiology*
  • nef Gene Products, Human Immunodeficiency Virus/physiology*
  • p21-Activated Kinases/metabolism
PubMed
19683683 Full text @ Cell Host Microbe
Abstract
HIV-1 Nef is a key factor in AIDS pathogenesis. Here, we report that Nef potently inhibits motility of fibroblasts and chemotaxis of HIV-1-infected primary human T lymphocytes toward the chemokines SDF-1alpha, CCL-19, and CCL-21 ex vivo. Furthermore, Nef inhibits guided motility of zebrafish primordial germ cells toward endogenous SDF-1a in vivo. These migration defects result from Nef-mediated inhibition of the actin remodeling normally triggered by migratory stimuli. Nef strongly induces phosphorylation of cofilin, inactivating this evolutionarily conserved actin-depolymerizing factor that promotes cell motility when unphosphorylated. Nef-dependent cofilin deregulation requires association of Nef with the cellular kinase Pak2. Disruption of Nef-Pak2 association restores the cofilin phosphorylation levels and actin remodeling that facilitate cell motility. We conclude that HIV-1 Nef alters Pak2 function, which directly or indirectly inactivates cofilin, thereby restricting migration of infected T lymphocytes as part of a strategy to optimize immune evasion and HIV-1 replication.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping