title: HIV-1 Nef-mediated T-cell activation and chemotaxis are decoupled using a HIV-1/SIVpbj1.9. chimeric nef variant.
abstract: HIV-1 Nef is known to activate CD4+ T cells but inhibit their migration toward SDF-1α. However, it is not clear how this protein orchestrates these two seemingly concomitant events. In this study, by comparing these two activities of HIV-1 Nef with those of its primate counterpart, SIVpbj1.9, we found that HIV-1 Nef activated T cells only in the presence of CD3/ CD28 stimulation, while SIVpbj1.9 Nef did even without CD3/CD28. We also observed that HIV-1 Nef inhibited T-cell chemotaxis toward SDF-1α, while SIVpbj1.9 Nef did not. A hybrid between HIV-1 and SIVpbj1.9 Nef completely abrogated the chemotaxis blockade by HIV-1 Nef while failing to activate T cells without CD3/CD28 co-stimulation. Mutations in the myristoylation and SH3-binding site, but not the basic-rich domain, in Nef were unresponsive to CD3/CD28 stimulation but reversed the inhibition of migration. These findings indicate that the signals for T-cell activation by Nef do not necessarily parallel those for T-cell migration.
authors.affiliation: Department of Cell Biology and Anatomy, Graduate School of Biomedical Sciences, University of North Texas Health Science Center, CBH-316, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, USA. inwoo.park@unthsc.edu
authors.forename: In-Woo
authors.initials: IW
authors.lastname: Park
authors.forename: Johnny J
authors.initials: JJ
authors.lastname: He
mesh_terms: D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015967:Gene Expression Regulation, Viral; D014644:Genetic Variation; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000502:physiology; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology* / Q000821:virology; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics* / Q000378:metabolism*
chemical_list: D018106:CD28 Antigens; D017252:CD3 Complex; D007376:Interleukin-2; D054311:nef Gene Products, Human Immunodeficiency Virus