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Naturally occurring...
Naturally occurring dipeptide from elite controllers with dual anti-HIV-1 mechanism
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- Cena-Diez, Rafael (author)
- Karolinska Institutet
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- Narayanan, Aswathy (author)
- Karolinska Inst, Dept Med Huddinge, Div Infect Dis, ANA Futura Lab, Stockholm, Sweden.
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- Ray, Shilpa (author)
- Karolinska Institutet
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- van de Klundert, Maarten (author)
- Karolinska Institutet
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- Rodriguez, Jimmy E. (author)
- Karolinska Inst, Dept Med Biochem & Biophys, Div Chem 1, Stockholm, Sweden.
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- Nilvebrant, Johan, 1982- (author)
- KTH,Proteinteknologi
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- Nygren, Per-Åke, 1961- (author)
- KTH,Proteinteknologi,Science for Life Laboratory, SciLifeLab
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- Vegvari, Akos (author)
- Karolinska Institutet
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- van Domselaar, Robert (author)
- Karolinska Institutet
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- Sonnerborg, Anders (author)
- Karolinska Institutet
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Karolinska Institutet Karolinska Inst, Dept Med Huddinge, Div Infect Dis, ANA Futura Lab, Stockholm, Sweden (creator_code:org_t)
- Elsevier BV, 2023
- 2023
- English.
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In: International Journal of Antimicrobial Agents. - : Elsevier BV. - 0924-8579 .- 1872-7913. ; 61:5, s. 106792-
- Related links:
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
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- Background: Enhanced levels of a dipeptide, WC-am, have been reported among elite controllers - patients who spontaneously control their HIV-1 infection. This study aimed to evaluate anti-HIV-1 activity and mechanism of action of WC-am.Methods: Drug sensitivity assays in TZM.bl cells, PBMCs and ACH-2 cells using WT and mutated HIV-1 strains were performed to evaluate the antiviral mechanism of WC-am. Mass spectrometry-based proteomics and Real-time PCR analysis of reverse transcription steps were performed to unravel the second anti-HIV-1 mechanism of WC-am.Results: The data suggest that WC-am binds to the CD4 binding pocket of HIV-1 gp120 and blocks its binding to the host cell receptors. Additionally, the time course assay showed that WC-am also inhibited HIV-1 at 4-6 hours post-infection, suggesting a second antiviral mechanism. Drug sensitivity assays under acidic wash conditions confirmed the ability of WC-am to internalise into the host cell in an HIV independent manner. Proteomic studies showed a clustering of all samples treated with WC-am independent of the number of doses or presence or absence of HIV-1. Differentially expressed proteins due to the WC-am treatment indicated an effect on HIV-1 reverse transcription, which was confirmed by reverse transcriptase polymerase chain reaction (RT-PCR).Conclusion: Naturally occurring in HIV-1 elite controllers, WC-am stands out as a new kind of antiviral compound with two independent inhibitory mechanisms of action on HIV-1 replication. WC-am halts HIV-1 entry to the host cell by binding to HIV-1 gp120, thereby blocking the binding of HIV-1 to the host cell. WC-am also exerts a post-entry but pre-integration antiviral effect related to RT-activity.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
Keyword
- Antiviral
- HIV
- Dual mechanism
- Entry
- Retrotranscription
- Therapy
Publication and Content Type
- ref (subject category)
- art (subject category)
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Cena-Diez, Rafae ...
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Narayanan, Aswat ...
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Ray, Shilpa
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van de Klundert, ...
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Rodriguez, Jimmy ...
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Nilvebrant, Joha ...
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show more...
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Nygren, Per-Åke, ...
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Vegvari, Akos
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van Domselaar, R ...
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Sonnerborg, Ande ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Infectious Medic ...
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Royal Institute of Technology
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Karolinska Institutet