Cited by 164HIV Research and TreatmentCellular transport and secretionT-cell and Retrovirus Studies

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

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Muratori, Claudia, Cavallin, Lucas E., Krätzel, Kirsten, Tinari, Antonella, De Milito, Angelo, Fais, Stefano, D'Aloja, Paola, Federico, Maurizio, Vullo, Vincenzo, Fomina, Alla, Mesri, Enrique A., Superti, Fabiana, Baur, Andreas S.·2009·Cell Host & Microbe

DOI 10.1016/j.chom.2009.06.009

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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.

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Madison, M. N., & Okeoma, C. M. (2015) · Viruses · doi:10.3390/v7072810 · Cited by 175
“There is evidence that HIV-1 infection or transduction of cells with the HIV-1 accessory protein, Nef, increases the cellular release of exosomes [34,76–78].”
Background

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Authors: Muratori, C., Cavallin, L. E., Krätzel, K., Tinari, A., De Milito, A., Fais, S., D'Aloja, P., Federico, M., Vullo, V., Fomina, A., Mesri, E. A., Superti, F., & Baur, A. S.
Affiliations: University of Miami (US)
Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
Istituto Superiore di Sanità (IT)
Sapienza University of Rome (IT)
University of California, Davis (US)
Corresponding author: Baur, Andreas S.
ORCID: Muratori, Claudia
Tinari, Antonella
Fais, Stefano
Federico, Maurizio
Fomina, Alla
Mesri, Enrique A.
Superti, Fabiana
Baur, Andreas S.
Venue: Cell Host & Microbe
Publisher: Elsevier BV
Published: 2009-09
Volume: 6
Issue: 3
Pages: 218-230
ISSN: 1931-3128 (ISSN-L)
DOI: 10.1016/j.chom.2009.06.009
OpenAlex: W1983073673
Semantic Scholar: 4882f11c55140c561fa862059b7d2ec9e08c0fa5
Cited by: 164
References: 82
Citations by year: 2026: 2 · 2025: 6 · 2024: 4 · 2023: 5 · 2022: 7 · 2021: 8 · 2020: 9 · 2019: 13 · 2018: 17 · 2017: 12 · 2016: 15 · 2015: 13 · 2014: 11 · 2013: 8 · 2012: 19
FWCI: 4.06
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 1415 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Cell Host & Microbe (publishedVersion)
PubMed (publishedVersion)
IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
Funders: National Cancer Institute (CA 75918, R01CA075918)
Topics: Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
Keywords: HIV Nef, exocytosis, endocytosis, microvesicles, bystander cells, cell-to-cell transmission, ERK signaling, membrane trafficking, CD4+ T cells, HIV pathogenesis
MeSH terms: Cells, Cultured, Endocytosis, Exocytosis, Humans, Lymphocyte Activation, T-Lymphocytes, HIV-1, HIV Infections, Protein Transport, Secretory Vesicles, Bystander Effect, nef Gene Products, Human Immunodeficiency Virus, Host-Pathogen Interactions, Secretory Pathway

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

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