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Research Article
Joachim Denner
Institute of Virology, Department of Veterinary Medicine, Free University Berlin
Corresponding Author
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Human immunodeficiency virus type 1 (HIV-1) persists lifelong in infected individuals and has evolved unique strategies in order to evade the immune system. One of these strategies is the direct cell-to-cell spread of HIV-1. The formation of a virological synapse (VS) between donor and target cell is important for this process. Tetraspanins are cellular proteins that are actively involved in the formation of a VS. However, the molecular mechanisms of recruiting host proteins for the cell-cell transfer of particles to the VS remains unclear. Our study has mapped the binding site for the transmembrane envelope protein gp41 of HIV-1 within the large extracellular loop (LEL) of CD63 and showed that this interaction occurs predominantly at the VS between T cells where viral particles are transferred. Mutations within the highly conserved CCG motif of the tetraspanin superfamily abrogated recruiting of expressed HIV-1 GFP fused Gag core protein and CD63 to the VS. This demonstrates the biological significance of CD63 for enhanced formation of a VS. Since cell-cell spread of HIV-1 is a major route of persistent infection, these results highlight the central role of CD63 as a member of the tetraspanin superfamily during HIV-1 infection and pathogenesis.
Keywords
Human immunodeficiency virus type 1 (HIV-1), immune system, Tetraspanins , large extracellular loop (LEL)
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CURRENT STATUS: Under Review
Version 1
Posted 28 Dec, 2020
No community comments so far
Editorial decision: Major revision
On 10 Feb, 2021
Reviews received
Received 29 Jan, 2021
Reviewers agreed
On 19 Jan, 2021
Reviewers agreed
On 07 Jan, 2021
Reviewers invited
Invitations sent on 04 Jan, 2021
Editor assigned
On 04 Jan, 2021
Editor invited
On 24 Dec, 2020
Submission checks complete
On 24 Dec, 2020
First submitted
On 08 Dec, 2020
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This preprint is under consideration at Scientific Reports. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Joachim Denner
Institute of Virology, Department of Veterinary Medicine, Free University Berlin
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 28 Dec, 2020
No community comments so far
Editorial decision: Major revision
On 10 Feb, 2021
Reviews received
Received 29 Jan, 2021
Reviewers agreed
On 19 Jan, 2021
Reviewers agreed
On 07 Jan, 2021
Reviewers invited
Invitations sent on 04 Jan, 2021
Editor assigned
On 04 Jan, 2021
Editor invited
On 24 Dec, 2020
Submission checks complete
On 24 Dec, 2020
First submitted
On 08 Dec, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Human immunodeficiency virus type 1 (HIV-1) persists lifelong in infected individuals and has evolved unique strategies in order to evade the immune system. One of these strategies is the direct cell-to-cell spread of HIV-1. The formation of a virological synapse (VS) between donor and target cell is important for this process. Tetraspanins are cellular proteins that are actively involved in the formation of a VS. However, the molecular mechanisms of recruiting host proteins for the cell-cell transfer of particles to the VS remains unclear. Our study has mapped the binding site for the transmembrane envelope protein gp41 of HIV-1 within the large extracellular loop (LEL) of CD63 and showed that this interaction occurs predominantly at the VS between T cells where viral particles are transferred. Mutations within the highly conserved CCG motif of the tetraspanin superfamily abrogated recruiting of expressed HIV-1 GFP fused Gag core protein and CD63 to the VS. This demonstrates the biological significance of CD63 for enhanced formation of a VS. Since cell-cell spread of HIV-1 is a major route of persistent infection, these results highlight the central role of CD63 as a member of the tetraspanin superfamily during HIV-1 infection and pathogenesis.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
This is a list of supplementary files associated with this preprint. Click to download.
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