| Cell-cell spread of human immunodeficiency virus type 1 overcomes tetherin/BST-2-mediated restriction in T cells. | |
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MedLine Citation:
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PMID: 20861257 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Direct cell-to-cell spread of human immunodeficiency virus type 1 (HIV-1) between T cells at the virological synapse (VS) is an efficient mechanism of viral dissemination. Tetherin (BST-2/CD317) is an interferon-induced, antiretroviral restriction factor that inhibits nascent cell-free particle release. The HIV-1 Vpu protein antagonizes tetherin activity; however, whether tetherin also restricts cell-cell spread is unclear. We performed quantitative cell-to-cell transfer analysis of wild-type (WT) or Vpu-defective HIV-1 in Jurkat and primary CD4(+) T cells, both of which express endogenous levels of tetherin. We found that Vpu-defective HIV-1 appeared to disseminate more efficiently by cell-to-cell contact between Jurkat cells under conditions where tetherin restricted cell-free virion release. In T cells infected with Vpu-defective HIV-1, tetherin was enriched at the VS, and VS formation was increased compared to the WT, correlating with an accumulation of virus envelope proteins on the cell surface. Increasing tetherin expression with type I interferon had only minor effects on cell-to-cell transmission. Furthermore, small interfering RNA (siRNA)-mediated depletion of tetherin decreased VS formation and cell-to-cell transmission of both Vpu-defective and WT HIV-1. Taken together, these data demonstrate that tetherin does not restrict VS-mediated T cell-to-T cell transfer of Vpu-defective HIV-1 and suggest that under some circumstances tetherin might promote cell-to-cell transfer, either by mediating the accumulation of virions on the cell surface or by regulating integrity of the VS. If so, inhibition of tetherin activity by Vpu may balance requirements for efficient cell-free virion production and cell-to-cell transfer of HIV-1 in the face of antiviral immune responses. |
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Authors:
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Clare Jolly; Nicola J Booth; Stuart J D Neil |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-22 |
Journal Detail:
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Title: Journal of virology Volume: 84 ISSN: 1098-5514 ISO Abbreviation: J. Virol. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-04 Completed Date: 2010-12-20 Revised Date: 2013-05-27 |
Medline Journal Info:
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Nlm Unique ID: 0113724 Medline TA: J Virol Country: United States |
Other Details:
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Languages: eng Pagination: 12185-99 Citation Subset: IM |
Affiliation:
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MRC Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, Windeyer Building, London, United Kingdom. c.jolly@ucl.ac.uk |
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| MeSH Terms | |
Descriptor/Qualifier:
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Antigens, CD
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metabolism* Blotting, Western CD4-Positive T-Lymphocytes / metabolism, virology* Electrophoresis, Polyacrylamide Gel Flow Cytometry Fluorescent Antibody Technique GPI-Linked Proteins / antagonists & inhibitors, metabolism HIV-1 / physiology* Human Immunodeficiency Virus Proteins / metabolism Humans Intercellular Junctions / ultrastructure, virology* Jurkat Cells Microscopy, Confocal Microscopy, Electron, Transmission RNA Interference Reverse Transcriptase Polymerase Chain Reaction Viral Regulatory and Accessory Proteins / metabolism Virion / physiology* Virus Replication / physiology* |
| Grant Support | |
ID/Acronym/Agency:
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G0800312//Medical Research Council; WT082774MA//Wellcome Trust |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD; 0/BST2 protein, human; 0/GPI-Linked Proteins; 0/Human Immunodeficiency Virus Proteins; 0/Viral Regulatory and Accessory Proteins; 0/vpu protein, Human immunodeficiency virus 1 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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