Document Detail


Cell-cell spread of human immunodeficiency virus type 1 overcomes tetherin/BST-2-mediated restriction in T cells.
MedLine Citation:
PMID:  20861257     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Clare Jolly; Nicola J Booth; Stuart J D Neil
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-22
Journal Detail:
Title:  Journal of virology     Volume:  84     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-04     Completed Date:  2010-12-20     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  12185-99     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Antigens, CD / 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:
G0800312//Medical Research Council; G0801937//Medical Research Council; WT082774MA//Wellcome Trust
Chemical
Reg. No./Substance:
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

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