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

104 Citations (Scopus)

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

Fingerprint

HIV
T-Lymphocytes
Exocytosis
Endocytosis
Human Immunodeficiency Virus nef Gene Products
Bystander Effect
Membranes
HIV Infections
Disease Progression
Phenotype

Keywords

  • CELLBIO
  • CELLIMMUNO
  • MICROBIO

ASJC Scopus subject areas

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

Cite this

Muratori, C., Cavallin, L. E., Krätzel, K., Tinari, A., De Milito, A., Fais, S., ... 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

Massive Secretion by T Cells Is Caused by HIV Nef in Infected Cells and by Nef Transfer to Bystander Cells. / Muratori, Claudia; Cavallin, Lucas E.; Krätzel, Kirsten; Tinari, Antonella; De Milito, Angelo; Fais, Stefano; D'Aloja, Paola; Federico, Maurizio; Vullo, Vincenzo; Fomina, Alla F; Mesri, Enrique A.; Superti, Fabiana; Baur, Andreas S.

In: Cell Host and Microbe, Vol. 6, No. 3, 17.09.2009, p. 218-230.

Research output: Contribution to journalArticle

Muratori, C, Cavallin, LE, Krätzel, K, Tinari, A, De Milito, A, Fais, S, D'Aloja, P, Federico, M, Vullo, V, Fomina, AF, Mesri, EA, Superti, F & Baur, AS 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, vol. 6, no. 3, pp. 218-230. https://doi.org/10.1016/j.chom.2009.06.009
Muratori, Claudia ; Cavallin, Lucas E. ; Krätzel, Kirsten ; Tinari, Antonella ; De Milito, Angelo ; Fais, Stefano ; D'Aloja, Paola ; Federico, Maurizio ; Vullo, Vincenzo ; Fomina, Alla F ; Mesri, Enrique A. ; Superti, Fabiana ; Baur, Andreas S. / Massive Secretion by T Cells Is Caused by HIV Nef in Infected Cells and by Nef Transfer to Bystander Cells. In: Cell Host and Microbe. 2009 ; Vol. 6, No. 3. pp. 218-230.
@article{45a01c824147484a83966d03837906ce,
title = "Massive Secretion by T Cells Is Caused by HIV Nef in Infected Cells and by Nef Transfer to Bystander Cells",
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.",
keywords = "CELLBIO, CELLIMMUNO, MICROBIO",
author = "Claudia Muratori and Cavallin, {Lucas E.} and Kirsten Kr{\"a}tzel and Antonella Tinari and {De Milito}, Angelo and Stefano Fais and Paola D'Aloja and Maurizio Federico and Vincenzo Vullo and Fomina, {Alla F} and Mesri, {Enrique A.} and Fabiana Superti and Baur, {Andreas S.}",
year = "2009",
month = "9",
day = "17",
doi = "10.1016/j.chom.2009.06.009",
language = "English (US)",
volume = "6",
pages = "218--230",
journal = "Cell Host and Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "3",

}

TY - JOUR

T1 - Massive Secretion by T Cells Is Caused by HIV Nef in Infected Cells and by Nef Transfer to Bystander Cells

AU - Muratori, Claudia

AU - Cavallin, Lucas E.

AU - Krätzel, Kirsten

AU - Tinari, Antonella

AU - De Milito, Angelo

AU - Fais, Stefano

AU - D'Aloja, Paola

AU - Federico, Maurizio

AU - Vullo, Vincenzo

AU - Fomina, Alla F

AU - Mesri, Enrique A.

AU - Superti, Fabiana

AU - Baur, Andreas S.

PY - 2009/9/17

Y1 - 2009/9/17

N2 - 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.

AB - 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.

KW - CELLBIO

KW - CELLIMMUNO

KW - MICROBIO

UR - http://www.scopus.com/inward/record.url?scp=69949128211&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=69949128211&partnerID=8YFLogxK

U2 - 10.1016/j.chom.2009.06.009

DO - 10.1016/j.chom.2009.06.009

M3 - Article

VL - 6

SP - 218

EP - 230

JO - Cell Host and Microbe

JF - Cell Host and Microbe

SN - 1931-3128

IS - 3

ER -