Autophagy receptor p62 regulates SARS-CoV-2-induced inflammation in COVID-19
Аутори
Stevanović, DanijelaPaunović, Verica
Vučićević, Ljubica
Misirkić Marjanović, Maja
Perović, Vladimir
Ristić, Biljana
Bošnjak, Mihajlo
Mandić, Miloš
Harhaji-Trajković, Ljubica
Janjetović, Kristina
Kosić, Milica
Lalošević, Jovan
Nikolić, Miloš
Bonaci-Nikolić, Branka
Trajković, Vladimir
Конференцијски прилог (Објављена верзија)
,
Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade
Метаподаци
Приказ свих података о документуАпстракт
Introduction: Since the interaction between autophagy and virus-induced inflammation is complex,
we investigated the interplay between autophagy and inflammation in COVID-19 patients and THP-1 cells expressing SARS-Cov2 proteins NSP5 and ORF3a. Methods: Autophagy markers in blood from 19 control subjects and 26 COVID-19 patients at hospital admission and one week later were measured by ELISA, while cytokine levels were examined by flow cytometric
bead immunoassay. The level of p62 in cells and its concentration in cell culture supernatants
was measured by immunoblot/ELISA. The mRNA levels of proinflammatory cytokines were measured by RT-qPCR.
Results: IFN-α, TNF, IL-6, IL-8, IL-17, IL-33, and IFN-γ were elevated in COVID-19 patients at both time points, whereas IL-10 and IL-1β were elevated at admission and one week later, respectively. Autophagy markers LC3 and ATG5 were unchanged in COVID-19. The concentration of autophagic cargo receptor p62 was significantly lower and positivel...y correlated with TNF, IL-10, IL-17, and IL-33 at hospital admission,returning to normal levels after one week. The expression of SARS-CoV-2 proteins NSP5 or ORF3a in THP-1 cells caused an autophagy-independent decrease/autophagy-inhibition-dependent increase of intracellular and secreted p62. This was associated with an NSP5-mediated decrease in TNF/IL-10 mRNA and an ORF3a-mediated increase in TNF/IL-1β/IL-6/IL-10/IL-33 mRNA levels. A genetic knockdown of p62 mimicked the immunosuppressive effect of NSP5, while a p62 increase in autophagy-deficient cells mirrored the immunostimulatory action of ORF3a. Conclusion: The autophagy receptor p62 is reduced in acute COVID-19, and the balance between autophagy-independent decrease and autophagy blockade-dependent increase of p62 levels could affect SARS-CoV-induced inflammation.
Кључне речи:
COVID19 / p62 / ORF3aИзвор:
CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia, 2023, 76-76Издавач:
- Belgrade: Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200007 (Универзитет у Београду, Институт за биолошка истраживања 'Синиша Станковић') (RS-MESTD-inst-2020-200007)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200110 (Универзитет у Београду, Медицински факултет) (RS-MESTD-inst-2020-200110)
Институција/група
Institut za medicinska istraživanjaTY - CONF AU - Stevanović, Danijela AU - Paunović, Verica AU - Vučićević, Ljubica AU - Misirkić Marjanović, Maja AU - Perović, Vladimir AU - Ristić, Biljana AU - Bošnjak, Mihajlo AU - Mandić, Miloš AU - Harhaji-Trajković, Ljubica AU - Janjetović, Kristina AU - Kosić, Milica AU - Lalošević, Jovan AU - Nikolić, Miloš AU - Bonaci-Nikolić, Branka AU - Trajković, Vladimir PY - 2023 UR - http://rimi.imi.bg.ac.rs/handle/123456789/1419 AB - Introduction: Since the interaction between autophagy and virus-induced inflammation is complex, we investigated the interplay between autophagy and inflammation in COVID-19 patients and THP-1 cells expressing SARS-Cov2 proteins NSP5 and ORF3a. Methods: Autophagy markers in blood from 19 control subjects and 26 COVID-19 patients at hospital admission and one week later were measured by ELISA, while cytokine levels were examined by flow cytometric bead immunoassay. The level of p62 in cells and its concentration in cell culture supernatants was measured by immunoblot/ELISA. The mRNA levels of proinflammatory cytokines were measured by RT-qPCR. Results: IFN-α, TNF, IL-6, IL-8, IL-17, IL-33, and IFN-γ were elevated in COVID-19 patients at both time points, whereas IL-10 and IL-1β were elevated at admission and one week later, respectively. Autophagy markers LC3 and ATG5 were unchanged in COVID-19. The concentration of autophagic cargo receptor p62 was significantly lower and positively correlated with TNF, IL-10, IL-17, and IL-33 at hospital admission,returning to normal levels after one week. The expression of SARS-CoV-2 proteins NSP5 or ORF3a in THP-1 cells caused an autophagy-independent decrease/autophagy-inhibition-dependent increase of intracellular and secreted p62. This was associated with an NSP5-mediated decrease in TNF/IL-10 mRNA and an ORF3a-mediated increase in TNF/IL-1β/IL-6/IL-10/IL-33 mRNA levels. A genetic knockdown of p62 mimicked the immunosuppressive effect of NSP5, while a p62 increase in autophagy-deficient cells mirrored the immunostimulatory action of ORF3a. Conclusion: The autophagy receptor p62 is reduced in acute COVID-19, and the balance between autophagy-independent decrease and autophagy blockade-dependent increase of p62 levels could affect SARS-CoV-induced inflammation. PB - Belgrade: Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade C3 - CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia T1 - Autophagy receptor p62 regulates SARS-CoV-2-induced inflammation in COVID-19 EP - 76 SP - 76 UR - https://hdl.handle.net/21.15107/rcub_rimi_1419 ER -
@conference{ author = "Stevanović, Danijela and Paunović, Verica and Vučićević, Ljubica and Misirkić Marjanović, Maja and Perović, Vladimir and Ristić, Biljana and Bošnjak, Mihajlo and Mandić, Miloš and Harhaji-Trajković, Ljubica and Janjetović, Kristina and Kosić, Milica and Lalošević, Jovan and Nikolić, Miloš and Bonaci-Nikolić, Branka and Trajković, Vladimir", year = "2023", abstract = "Introduction: Since the interaction between autophagy and virus-induced inflammation is complex, we investigated the interplay between autophagy and inflammation in COVID-19 patients and THP-1 cells expressing SARS-Cov2 proteins NSP5 and ORF3a. Methods: Autophagy markers in blood from 19 control subjects and 26 COVID-19 patients at hospital admission and one week later were measured by ELISA, while cytokine levels were examined by flow cytometric bead immunoassay. The level of p62 in cells and its concentration in cell culture supernatants was measured by immunoblot/ELISA. The mRNA levels of proinflammatory cytokines were measured by RT-qPCR. Results: IFN-α, TNF, IL-6, IL-8, IL-17, IL-33, and IFN-γ were elevated in COVID-19 patients at both time points, whereas IL-10 and IL-1β were elevated at admission and one week later, respectively. Autophagy markers LC3 and ATG5 were unchanged in COVID-19. The concentration of autophagic cargo receptor p62 was significantly lower and positively correlated with TNF, IL-10, IL-17, and IL-33 at hospital admission,returning to normal levels after one week. The expression of SARS-CoV-2 proteins NSP5 or ORF3a in THP-1 cells caused an autophagy-independent decrease/autophagy-inhibition-dependent increase of intracellular and secreted p62. This was associated with an NSP5-mediated decrease in TNF/IL-10 mRNA and an ORF3a-mediated increase in TNF/IL-1β/IL-6/IL-10/IL-33 mRNA levels. A genetic knockdown of p62 mimicked the immunosuppressive effect of NSP5, while a p62 increase in autophagy-deficient cells mirrored the immunostimulatory action of ORF3a. Conclusion: The autophagy receptor p62 is reduced in acute COVID-19, and the balance between autophagy-independent decrease and autophagy blockade-dependent increase of p62 levels could affect SARS-CoV-induced inflammation.", publisher = "Belgrade: Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade", journal = "CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia", title = "Autophagy receptor p62 regulates SARS-CoV-2-induced inflammation in COVID-19", pages = "76-76", url = "https://hdl.handle.net/21.15107/rcub_rimi_1419" }
Stevanović, D., Paunović, V., Vučićević, L., Misirkić Marjanović, M., Perović, V., Ristić, B., Bošnjak, M., Mandić, M., Harhaji-Trajković, L., Janjetović, K., Kosić, M., Lalošević, J., Nikolić, M., Bonaci-Nikolić, B.,& Trajković, V.. (2023). Autophagy receptor p62 regulates SARS-CoV-2-induced inflammation in COVID-19. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia Belgrade: Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade., 76-76. https://hdl.handle.net/21.15107/rcub_rimi_1419
Stevanović D, Paunović V, Vučićević L, Misirkić Marjanović M, Perović V, Ristić B, Bošnjak M, Mandić M, Harhaji-Trajković L, Janjetović K, Kosić M, Lalošević J, Nikolić M, Bonaci-Nikolić B, Trajković V. Autophagy receptor p62 regulates SARS-CoV-2-induced inflammation in COVID-19. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia. 2023;:76-76. https://hdl.handle.net/21.15107/rcub_rimi_1419 .
Stevanović, Danijela, Paunović, Verica, Vučićević, Ljubica, Misirkić Marjanović, Maja, Perović, Vladimir, Ristić, Biljana, Bošnjak, Mihajlo, Mandić, Miloš, Harhaji-Trajković, Ljubica, Janjetović, Kristina, Kosić, Milica, Lalošević, Jovan, Nikolić, Miloš, Bonaci-Nikolić, Branka, Trajković, Vladimir, "Autophagy receptor p62 regulates SARS-CoV-2-induced inflammation in COVID-19" in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia (2023):76-76, https://hdl.handle.net/21.15107/rcub_rimi_1419 .