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Genome-scale metabo...
Genome-scale metabolic models for natural and long-term drug-induced viral control in HIV infection
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- Ambikan, Anoop T. (författare)
- Karolinska Institutet
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- Svensson-Akusjärvi, Sara (författare)
- Karolinska Institutet
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Krishnan, Shuba (författare)
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- Sperk, Maike (författare)
- Karolinska Institutet
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- Nowak, Piotr (författare)
- Karolinska Institutet
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- Vesterbacka, Jan (författare)
- Karolinska Institutet
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- Sönnerborg, Anders (författare)
- Karolinska Institutet
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- Benfeitas, Rui (författare)
- Stockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab)
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- Neogi, Ujjwal (författare)
- Karolinska Institutet
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(creator_code:org_t)
- 2022-05-10
- 2022
- Engelska.
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Ingår i: Life Science Alliance. - : Life Science Alliance, LLC. - 2575-1077. ; 5:9
- Relaterad länk:
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https://doi.org/10.2...
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https://urn.kb.se/re...
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https://doi.org/10.2...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Genome-scale metabolic models (GSMMs) can provide novel insights into metabolic reprogramming during disease progression and therapeutic interventions. We developed a context-specific system-level GSMM of people living with HIV (PLWH) using global RNA sequencing data from PBMCs with suppressive viremia either by natural (elite controllers, PLWHEC) or drug-induced (PLWHART) control. This GSMM was compared with HIV-negative controls (HC) to provide a comprehensive systems-level metabo-transcriptomic characterization. Transcriptomic analysis identified up-regulation of oxidative phosphorylation as a characteristic of PLWHART, differentiating them from PLWHEC with dysregulated complexes I, III, and IV. The flux balance analysis identified altered flux in several intermediates of glycolysis including pyruvate, a-ketoglutarate, and glutamate, among others, in PLWHART. The in vitro pharmacological inhibition of OXPHOS complexes in a latent lymphocytic cell model (J-Lat 10.6) suggested a role for complex IV in latency reversal and immunosenescence. Furthermore, inhibition of complexes I/III/IV induced apoptosis, collectively indicating their contribution to reservoir dynamics.
Ämnesord
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
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