Insights into coronavirus immunity taught by the murine coronavirus

Grabherr, Sarah; Ludewig, Burkhard; Pikor, Natalia

doi:10.1002/eji.202048984

Cited by 18 publications

(19 citation statements)

References 63 publications

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“…Laboratory MHV strains have been broadly studied to identify harmful coronavirus factors and elucidate host mechanisms of antiviral pathogenicity (see, [ 65 , 66 , 67 , 68 ] and references therein). The major MHV viruses used are MHV-3, MHV-A59, MHV-JHM, and MHV-S.…”

Section: Discussionmentioning

confidence: 99%

Multi-Organ Histopathological Changes in a Mouse Hepatitis Virus Model of COVID-19

Paidas

Mohamed

Norenberg

et al. 2021

Viruses

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Infection with SARS-CoV-2, the virus responsible for the global COVID-19 pandemic, causes a respiratory illness that can severely impact other organ systems and is possibly precipitated by cytokine storm, septic shock, thrombosis, and oxidative stress. SARS-CoV-2 infected individuals may be asymptomatic or may experience mild, moderate, or severe symptoms with or without pneumonia. The mechanisms by which SARS-CoV-2 infects humans are largely unknown. Mouse hepatitis virus 1 (MHV-1)-induced infection was used as a highly relevant surrogate animal model for this study. We further characterized this animal model and compared it with SARS-CoV-2 infection in humans. MHV-1 inoculated mice displayed death as well as weight loss, as reported earlier. We showed that MHV-1-infected mice at days 7–8 exhibit severe lung inflammation, peribronchiolar interstitial infiltration, bronchiolar epithelial cell necrosis and intra-alveolar necrotic debris, alveolar exudation (surrounding alveolar walls have capillaries that are dilated and filled with red blood cells), mononuclear cell infiltration, hyaline membrane formation, the presence of hemosiderin-laden macrophages, and interstitial edema. When compared to uninfected mice, the infected mice showed severe liver vascular congestion, luminal thrombosis of portal and sinusoidal vessels, hepatocyte degeneration, cell necrosis, and hemorrhagic changes. Proximal and distal tubular necrosis, hemorrhage in interstitial tissue, and the vacuolation of renal tubules were observed. The heart showed severe interstitial edema, vascular congestion, and dilation, as well as red blood cell extravasation into the interstitium. Upon examination of the MHV-1 infected mice brain, we observed congested blood vessels, perivascular cavitation, cortical pericellular halos, vacuolation of neuropils, darkly stained nuclei, pyknotic nuclei, and associated vacuolation of the neuropil in the cortex, as well as acute eosinophilic necrosis and necrotic neurons with fragmented nuclei and vacuolation in the hippocampus. Our findings suggest that the widespread thrombotic events observed in the surrogate animal model for SARS-CoV-2 mimic the reported findings in SARS-CoV-2 infected humans, representing a highly relevant and safe animal model for the study of the pathophysiologic mechanisms of SARS-CoV-2 for potential therapeutic interventions.

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Section: Discussionmentioning

confidence: 99%

Multi-Organ Histopathological Changes in a Mouse Hepatitis Virus Model of COVID-19

Paidas

Mohamed

Norenberg

et al. 2021

Viruses

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“…The infection with the human CoV is commonly associated with mild respiratory symptoms. However, the emergence of beta subgroup CoV strains, including SARS-CoV-1, MERS-CoV, and SARS-CoV-2, highlights the potential of CoV to cause severe respiratory and systemic disease (Van Der Hoek et al, 2004;Sariol and Perlman, 2020;Grabherr et al, 2021). SARS-CoV-1-infected individuals were first reported in 2002 with approximately 8100 reported cases (Peng et al, 2003;Zhao et al, 2003;Sariol and Perlman, 2020).…”

Section: Introductionmentioning

confidence: 99%

T cell responses to SARS-CoV-2 in humans and animals

Mattoo

Myoung

2022

J Microbiol.

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SARS-CoV-2, the causative agent of COVID-19, first emerged in 2019. Antibody responses against SARS-CoV-2 have been given a lot of attention. However, the armamentarium of humoral and T cells may have differing roles in different viral infections. Though the exact role of T cells in COVID-19 remains to be elucidated, prior experience with human coronavirus has revealed an essential role of T cells in the outcomes of viral infections. Moreover, an increasing body of evidence suggests that T cells might be effective against SARS-CoV-2. This review summarizes the role of T cells in mouse CoV, human pathogenic respiratory CoV in general and SARS-CoV-2 in specific.

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“…In a previous study, it has been shown that MHV shares inhibitory effects for virus entry with SARS-CoV-2 [ 34 ]. Furthermore, MHV is closely related to pro-inflammatory response, similar to SARS-CoV-2, including induction of cytokines such as TNF and IL-1β, and IFN-gamma [ 35 ]. Additionally, MHV and SARS-CoV-2 have typical decay patterns in an environment [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Activation of TCA cycle restrains virus-metabolic hijacking and viral replication in mouse hepatitis virus-infected cells

et al. 2022

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Background One of coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused coronavirus disease 2019 (COVID-19) pandemic and threatened worldwide. However, therapy for COVID-19 has rarely been proven to possess specific efficacy. As the virus relies on host metabolism for its survival, several studies have reported metabolic intervention by SARS-CoV-2. Results We investigated the coronavirus-metabolic hijacking using mouse hepatitis virus (MHV) as a surrogate for SARS-CoV-2. Based on the altered host metabolism by MHV infection, an increase of glycolysis with low mitochondrial metabolism, we tried to investigate possible therapeutic molecules which increase the TCA cycle. Endogenous metabolites and metabolic regulators were introduced to restrain viral replication by metabolic intervention. We observed that cells deprived of cellular energy nutrition with low glycolysis strongly suppress viral replication. Furthermore, viral replication was also significantly suppressed by electron transport chain inhibitors which exhaust cellular energy. Apart from glycolysis and ETC, pyruvate supplement suppressed viral replication by the TCA cycle induction. As the non-glucose metabolite, fatty acids supplement decreased viral replication via the TCA cycle. Additionally, as a highly possible therapeutic metabolite, nicotinamide riboside (NR) supplement, which activates the TCA cycle by supplying NAD+, substantially suppressed viral replication. Conclusions This study suggests that metabolite-mediated TCA cycle activation suppresses replication of coronavirus and suggests that NR might play a role as a novel therapeutic metabolite for coronavirus.

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Insights into coronavirus immunity taught by the murine coronavirus

Cited by 18 publications

References 63 publications

Multi-Organ Histopathological Changes in a Mouse Hepatitis Virus Model of COVID-19

Multi-Organ Histopathological Changes in a Mouse Hepatitis Virus Model of COVID-19

T cell responses to SARS-CoV-2 in humans and animals

Activation of TCA cycle restrains virus-metabolic hijacking and viral replication in mouse hepatitis virus-infected cells

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