HIV-1 Nef interferes with host cell motility by deregulation of Cofilin. 2009

Bettina Stolp, and Michal Reichman-Fried, and Libin Abraham, and Xiaoyu Pan, and Simone I Giese, and Sebastian Hannemann, and Polyxeni Goulimari, and Erez Raz, and Robert Grosse, and Oliver T Fackler
Department of Virology, Im Neuenheimer Feld 324, University of Heidelberg, Heidelberg 69120, Germany.

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.

UI MeSH Term Description Entries
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002465 Cell Movement The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell. Cell Migration,Locomotion, Cell,Migration, Cell,Motility, Cell,Movement, Cell,Cell Locomotion,Cell Motility,Cell Movements,Movements, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D005347 Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Fibroblast
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013601 T-Lymphocytes Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T Cell,T Lymphocyte,T-Cells,Thymus-Dependent Lymphocytes,Cell, T,Cells, T,Lymphocyte, T,Lymphocyte, Thymus-Dependent,Lymphocytes, T,Lymphocytes, Thymus-Dependent,T Cells,T Lymphocytes,T-Cell,T-Lymphocyte,Thymus Dependent Lymphocytes,Thymus-Dependent Lymphocyte
D015497 HIV-1 The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte. Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human
D051339 Actin Depolymerizing Factors A family of low MOLECULAR WEIGHT actin-binding proteins found throughout eukaryotes. They remodel the actin CYTOSKELETON by severing ACTIN FILAMENTS and increasing the rate of monomer dissociation. Actin Depolymerizing Protein,Cofilin,Cofilins,ADF Proteins (Actin Depolymerizing Factors),Actin Depolymerizing Proteins,Cofilin Proteins,Depolymerizing Factors, Actin,Depolymerizing Protein, Actin,Depolymerizing Proteins, Actin,Protein, Actin Depolymerizing
D054311 nef Gene Products, Human Immunodeficiency Virus Proteins encoded by the NEF GENES of the HUMAN IMMUNODEFICIENCY VIRUS. nef Protein, Human Immunodeficiency Virus,HIV-3'-orf Protein,nef Protein, HIV,HIV 3' orf Protein,HIV nef Protein
D054462 p21-Activated Kinases A family of serine-threonine kinases that bind to and are activated by MONOMERIC GTP-BINDING PROTEINS such as RAC GTP-BINDING PROTEINS and CDC42 GTP-BINDING PROTEIN. They are intracellular signaling kinases that play a role the regulation of cytoskeletal organization. PAK Kinase,p21-Activated Kinase,Oligophrenin-3,PAK Kinases,PAK-1 Kinase,PAK-2 Kinase,PAK1 Kinase,PAK2 Kinase,PAK3 Kinase,PAK65,Serine-Threonine-Protein Kinase PAK 1,Serine-Threonine-Protein Kinase PAK 3,alpha p21-Activated Kinase,alpha-PAK,beta p21-Activated Kinase,beta-PAK,gamma-PAK,p21-Activated Kinase 1,p21-Activated Kinase 2,p21-Activated Kinase 3,p65(PAK),p65PAK Protein,Kinase, PAK,Kinase, p21-Activated,Kinases, PAK,Kinases, p21-Activated,Oligophrenin 3,PAK 1 Kinase,PAK 2 Kinase,Serine Threonine Protein Kinase PAK 1,Serine Threonine Protein Kinase PAK 3,alpha p21 Activated Kinase,beta p21 Activated Kinase,gamma PAK,p21 Activated Kinase,p21 Activated Kinase 1,p21 Activated Kinase 2,p21 Activated Kinase 3,p21 Activated Kinases,p21-Activated Kinase, beta

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