학술논문
COVID-19 Induces Neuroinflammation and Suppresses Peroxisomes in the Brain.
Document Type
Academic Journal
Author
Roczkowsky A; Department of Medicine, University of Alberta, Edmonton, AB, USA.; Limonta D; Department of Cell Biology, University of Alberta, Edmonton, AB, USA.; Li Ka Shing Institute of Virology, University of Alberta, Edmonton, AB, USA.; Fernandes JP; Department of Medical Microbiology & Immunology, University of Alberta, Edmonton, AB, USA.; Branton WG; Department of Medicine, University of Alberta, Edmonton, AB, USA.; Clarke M; Department of Medicine, University of Alberta, Edmonton, AB, USA.; Hlavay B; Department of Medicine, University of Alberta, Edmonton, AB, USA.; Noyce RS; Department of Medical Microbiology & Immunology, University of Alberta, Edmonton, AB, USA.; Joseph JT; Department of Pathology, University of Calgary, Calgary, AB, USA.; Ogando NS; Department of Medicine, University of Alberta, Edmonton, AB, USA.; Das SK; Department of Laboratory Medicine & Pathology, University of Alberta, Edmonton, AB, USA.; Elaish M; Department of Cell Biology, University of Alberta, Edmonton, AB, USA.; Arbour N; Department of Neuroscience, University of Montreal, and CHUM, Montreal, QC, Canada.; Evans DH; Department of Medical Microbiology & Immunology, University of Alberta, Edmonton, AB, USA.; Langdon K; Department of Pathology, University of Calgary, Calgary, AB, USA.; Hobman TC; Department of Cell Biology, University of Alberta, Edmonton, AB, USA.; Li Ka Shing Institute of Virology, University of Alberta, Edmonton, AB, USA.; Department of Medical Microbiology & Immunology, University of Alberta, Edmonton, AB, USA.; Power C; Department of Medicine, University of Alberta, Edmonton, AB, USA.; Department of Medical Microbiology & Immunology, University of Alberta, Edmonton, AB, USA.
Source
Publisher: Wiley-Liss Country of Publication: United States NLM ID: 7707449 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1531-8249 (Electronic) Linking ISSN: 03645134 NLM ISO Abbreviation: Ann Neurol Subsets: MEDLINE
Subject
Language
English
Abstract
Objective: Peroxisome injury occurs in the central nervous system (CNS) during multiple virus infections that result in neurological disabilities. We investigated host neuroimmune responses and peroxisome biogenesis factors during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using a multiplatform strategy.
Methods: Brain tissues from coronavirus disease 2019 (COVID-19) (n = 12) and other disease control (ODC) (n = 12) patients, as well as primary human neural cells and Syrian hamsters, infected with a clinical variant of SARS-CoV-2, were investigated by droplet digital polymerase chain reaction (ddPCR), quantitative reverse transcriptase PCR (RT-qPCR), and immunodetection methods.
Results: SARS-CoV-2 RNA was detected in the CNS of 4 patients with COVID-19 with viral protein (NSP3 and spike) immunodetection in the brainstem. Olfactory bulb, brainstem, and cerebrum from patients with COVID-19 showed induction of pro-inflammatory transcripts (IL8, IL18, CXCL10, NOD2) and cytokines (GM-CSF and IL-18) compared to CNS tissues from ODC patients (p < 0.05). Peroxisome biogenesis factor transcripts (PEX3, PEX5L, PEX11β, and PEX14) and proteins (PEX3, PEX14, PMP70) were suppressed in the CNS of COVID-19 compared to ODC patients (p < 0.05). SARS-CoV-2 infection of hamsters revealed viral RNA detection in the olfactory bulb at days 4 and 7 post-infection while inflammatory gene expression was upregulated in the cerebrum of infected animals by day 14 post-infection (p < 0.05). Pex3 transcript levels together with catalase and PMP70 immunoreactivity were suppressed in the cerebrum of SARS-CoV-2 infected animals (p < 0.05).
Interpretation: COVID-19 induced sustained neuroinflammatory responses with peroxisome biogenesis factor suppression despite limited brainstem SARS-CoV-2 neurotropism in humans. These observations offer insights into developing biomarkers and therapies, while also implicating persistent peroxisome dysfunction as a contributor to the neurological post-acute sequelae of COVID-19. ANN NEUROL 2023;94:531-546.
(© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)
Methods: Brain tissues from coronavirus disease 2019 (COVID-19) (n = 12) and other disease control (ODC) (n = 12) patients, as well as primary human neural cells and Syrian hamsters, infected with a clinical variant of SARS-CoV-2, were investigated by droplet digital polymerase chain reaction (ddPCR), quantitative reverse transcriptase PCR (RT-qPCR), and immunodetection methods.
Results: SARS-CoV-2 RNA was detected in the CNS of 4 patients with COVID-19 with viral protein (NSP3 and spike) immunodetection in the brainstem. Olfactory bulb, brainstem, and cerebrum from patients with COVID-19 showed induction of pro-inflammatory transcripts (IL8, IL18, CXCL10, NOD2) and cytokines (GM-CSF and IL-18) compared to CNS tissues from ODC patients (p < 0.05). Peroxisome biogenesis factor transcripts (PEX3, PEX5L, PEX11β, and PEX14) and proteins (PEX3, PEX14, PMP70) were suppressed in the CNS of COVID-19 compared to ODC patients (p < 0.05). SARS-CoV-2 infection of hamsters revealed viral RNA detection in the olfactory bulb at days 4 and 7 post-infection while inflammatory gene expression was upregulated in the cerebrum of infected animals by day 14 post-infection (p < 0.05). Pex3 transcript levels together with catalase and PMP70 immunoreactivity were suppressed in the cerebrum of SARS-CoV-2 infected animals (p < 0.05).
Interpretation: COVID-19 induced sustained neuroinflammatory responses with peroxisome biogenesis factor suppression despite limited brainstem SARS-CoV-2 neurotropism in humans. These observations offer insights into developing biomarkers and therapies, while also implicating persistent peroxisome dysfunction as a contributor to the neurological post-acute sequelae of COVID-19. ANN NEUROL 2023;94:531-546.
(© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)