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Genome-scale metabolic models for natural and long-term drug-induced viral control in HIV infection
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Rekke forfattare: 92022 (engelsk)Inngår i: Life Science Alliance, E-ISSN 2575-1077, Vol. 5, nr 9, artikkel-id e202201405Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

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.

sted, utgiver, år, opplag, sider
2022. Vol. 5, nr 9, artikkel-id e202201405
HSV kategori
Identifikatorer
URN: urn:nbn:se:su:diva-205219DOI: 10.26508/lsa.202201405ISI: 000798548300001PubMedID: 35537851Scopus ID: 2-s2.0-85130003381OAI: oai:DiVA.org:su-205219DiVA, id: diva2:1664468
Tilgjengelig fra: 2022-06-03 Laget: 2022-06-03 Sist oppdatert: 2022-06-03bibliografisk kontrollert

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