Massive Secretion by T Cells Is Caused by HIV Nef in Infected Cells and by Nef Transfer to Bystander Cells

Claudia Muratori, Lucas E. Cavallin, Kirsten Krätzel, Antonella Tinari, Angelo De Milito, Stefano Fais, Paola D'Aloja, Maurizio Federico, Vincenzo Vullo, Alla F Fomina, Enrique A. Mesri, Fabiana Superti, Andreas S. Baur

Research output: Contribution to journalArticle

114 Scopus citations

Abstract

The HIV Nef protein mediates endocytosis of surface receptors that correlates with disease progression, but the link between this Nef function and HIV pathogenesis is not clear. Here, we report that Nef-mediated activation of membrane trafficking is bidirectional, connecting endocytosis with exocytosis as occurs in activated T cells. Nef expression induced an extensive secretory activity in infected and, surprisingly, also in noninfected T cells, leading to the massive release of microvesicle clusters, a phenotype observed in vitro and in 36%-87% of primary CD4 T cells from HIV-infected individuals. Consistent with exocytosis in noninfected cells, Nef is transferred to bystander cells upon cell-to-cell contact and subsequently induces secretion in an Erk1/2-dependent manner. Thus, HIV Nef alters membrane dynamics, mimicking those of activated T cells and causing a transfer of infected cell signaling (TOS) to bystander cells. This mechanism may help explain the detrimental effect on bystander cells seen in HIV infection.

Original languageEnglish (US)
Pages (from-to)218-230
Number of pages13
JournalCell Host and Microbe
Volume6
Issue number3
DOIs
StatePublished - Sep 17 2009

Keywords

  • CELLBIO
  • CELLIMMUNO
  • MICROBIO

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Cancer Research
  • Molecular Biology

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    Muratori, C., Cavallin, L. E., Krätzel, K., Tinari, A., De Milito, A., Fais, S., D'Aloja, P., Federico, M., Vullo, V., Fomina, A. F., Mesri, E. A., Superti, F., & Baur, A. S. (2009). Massive Secretion by T Cells Is Caused by HIV Nef in Infected Cells and by Nef Transfer to Bystander Cells. Cell Host and Microbe, 6(3), 218-230. https://doi.org/10.1016/j.chom.2009.06.009