The DOI matches its Crossref record; 81 of the 82 references it cites were found in a registry or an index.
Massive Secretion by T Cells Is Caused by HIV Nef in Infected Cells and by Nef Transfer to Bystander Cells
Open accessAbstract
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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In the citing paper
“One common feature in these studies is that the MVBs involved may not be classical late-endosomes.”
From GAPDH controls extracellular vesicle biogenesis and enhances the therapeutic potential of EV mediated siRNA delivery to the brain (2021) · cites this paper as [64]
In the citing paper
“Indeed, clustered ILVs have been observed in other cell types in mammals and nematodes in the absence of DCGs and in specific pathological scenarios36,64.”
From GAPDH controls extracellular vesicle biogenesis and enhances the therapeutic potential of EV mediated siRNA delivery to the brain (2021) · cites this paper as [64]
Citations
Cites
1 retracted
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B lymphocytes secrete antigen-presenting vesicles.
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Shedding microvesicles: artefacts no more
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Self-citationSpread of HTLV-I Between Lymphocytes by Virus-Induced Polarization of the Cytoskeleton
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Mathieu, M., Jaular, L. M., Lavieu, G., & Théry, C. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0250-9 · Cited by 3,894
Witwer, K. W., Buzás, E. I., Bemis, L., Bora, A., Lässer, C., Lötvall, J. O., Hoen, E. N. M. N., Piper, M. G., Sivaraman, S., Skog, J., et al. (2013) · Journal of Extracellular Vesicles · doi:10.3402/jev.v2i0.20360 · Cited by 2,513
Microvesicles and Viral Infection
Meckes, D. G., & Raab‐Traub, N. (2011) · Journal of Virology · doi:10.1128/jvi.05853-11 · Cited by 401
Exosomes Derived from HIV-1-infected Cells Contain Trans-activation Response Element RNA
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Exosomes: Implications in HIV-1 Pathogenesis
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
Metadata
- 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
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2009-09
- Volume
- 6
- Issue
- 3
- Pages
- 218-230
- ISSN
- 1931-3128 (ISSN-L)
- 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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