Murine Hepatitis Virus, a Biosafety Level 2 Model for SARS-CoV-2, Can Remain Viable on Meat and Meat Packaging Materials for at Least 48 Hours

Featherstone, Austin B; Brown, Alexander; Dass, Sapna Chitlapilly

doi:10.1128/spectrum.01862-22

Cited by 5 publications

(6 citation statements)

References 54 publications

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“…We used MHV to investigate RA’s antiviral properties during coronavirus infection [ 32 , 33 , 34 , 35 ]. Similar to human coronaviruses, MHV can inhibit the type-I IFN response and infect lung tissue [ 15 , 16 , 36 , 37 ].…”

Section: Resultsmentioning

confidence: 99%

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Retinoic Acid-Mediated Inhibition of Mouse Coronavirus Replication Is Dependent on IRF3 and CaMKK

Franco,

Harris,

Ryan

et al. 2024

Viruses

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The ongoing COVID-19 pandemic has revealed the shortfalls in our understanding of how to treat coronavirus infections. With almost 7 million case fatalities of COVID-19 globally, the catalog of FDA-approved antiviral therapeutics is limited compared to other medications, such as antibiotics. All-trans retinoic acid (RA), or activated vitamin A, has been studied as a potential therapeutic against coronavirus infection because of its antiviral properties. Due to its impact on different signaling pathways, RA’s mechanism of action during coronavirus infection has not been thoroughly described. To determine RA’s mechanism of action, we examined its effect against a mouse coronavirus, mouse hepatitis virus strain A59 (MHV). We demonstrated that RA significantly decreased viral titers in infected mouse L929 fibroblasts and RAW 264.7 macrophages. The reduced viral titers were associated with a corresponding decrease in MHV nucleocapsid protein expression. Using interferon regulatory factor 3 (IRF3) knockout RAW 264.7 cells, we demonstrated that RA-induced suppression of MHV required IRF3 activity. RNA-seq analysis of wildtype and IRF3 knockout RAW cells showed that RA upregulated calcium/calmodulin (CaM) signaling proteins, such as CaM kinase kinase 1 (CaMKK1). When treated with a CaMKK inhibitor, RA was unable to upregulate IRF activation during MHV infection. In conclusion, our results demonstrate that RA-induced protection against coronavirus infection depends on IRF3 and CaMKK.

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Section: Resultsmentioning

confidence: 99%

“…Likewise, RA is well tolerated by L929 fibroblasts and exhibits negligible cell toxicity (Figure S1). [32][33][34][35]. Similar to human coronaviruses, MHV can inhibit the type-I IFN response and infect lung tissue [15,16,36,37].…”

Section: Ra Confers Protection Against Mhv Infectionmentioning

confidence: 99%

Retinoic Acid-Mediated Inhibition of Mouse Coronavirus Replication Is Dependent on IRF3 and CaMKK

Franco,

Harris,

Ryan

et al. 2024

Viruses

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“…Murine hepatitis virus and SARS-CoV-2 are both members of the genus Betacoronavirus [ 32 ] and have similar genome structure and biology. Humans are not susceptible to MHV infection, making it safer and easier to perform testing with MHV since it does not require a BSL-3 laboratory setting [ 33 , 34 , 35 ]. Virulence and organotropism of MHV depends on the virus strain and varies as multiple strains exist.…”

Section: Introductionmentioning

confidence: 99%

Antiviral Effect of Antimicrobial Peptoid TM9 and Murine Model of Respiratory Coronavirus Infection

Lebedev,

Benjamin,

Kumar

et al. 2024

Pharmaceutics

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New antiviral agents are essential to improving treatment and control of SARS-CoV-2 infections that can lead to the disease COVID-19. Antimicrobial peptoids are sequence-specific oligo-N-substituted glycine peptidomimetics that emulate the structure and function of natural antimicrobial peptides but are resistant to proteases. We demonstrate antiviral activity of a new peptoid (TM9) against the coronavirus, murine hepatitis virus (MHV), as a closely related model for the structure and antiviral susceptibility profile of SARS-CoV-2. This peptoid mimics the human cathelicidin LL-37, which has also been shown to have antimicrobial and antiviral activity. In this study, TM9 was effective against three murine coronavirus strains, demonstrating that the therapeutic window is large enough to allow the use of TM9 for treatment. All three isolates of MHV generated infection in mice after 15 min of exposure by aerosol using the Madison aerosol chamber, and all three viral strains could be isolated from the lungs throughout the 5-day observation period post-infection, with the peak titers on day 2. MHV-A59 and MHV-A59-GFP were also isolated from the liver, heart, spleen, olfactory bulbs, and brain. These data demonstrate that MHV serves as a valuable natural murine model of coronavirus pathogenesis in multiple organs, including the brain.

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“…As it is known that SARS-CoV-2, the etiologic agent of COVID-19, is a risk group 3 (RG-3) pathogen, drug development has been hindered by the lack of BSL-3 facilities. Alternative strategies have been exploited to circumvent this limitation, including using pseudotyped virus [ 31 ] or murine hepatitis virus (MHV) as a surrogate model for the study of SARS-CoV entry or replication, respectively [ 32 , 33 , 34 ]. MHV belongs to the β-coronavirus, in the same subgenus of SARS-CoV-2, and it could be an excellent model to investigate the pathogenesis in the aspects of virulence and immune response to coronaviruses including SARS-CoV.…”

Section: Introductionmentioning

confidence: 99%

Strictinin, a Major Ingredient in Yunnan Kucha Tea Possessing Inhibitory Activity on the Infection of Mouse Hepatitis Virus to Mouse L Cells

Hsu

Tzen

2023

Molecules

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Theacrine and strictinin of Yunnan Kucha tea prepared from a mutant variety of wild Pu’er tea plants were two major ingredients responsible for the anti-influenza activity. As the COVID-19 outbreak is still lurking, developing safe and cost-effective therapeutics is an urgent need. This study aimed to evaluate the effects of these tea compounds on the infection of mouse hepatitis virus (MHV), a β-coronavirus serving as a surrogate for SARS-CoV. Treatment with strictinin (100 μM), but not theacrine, completely eliminated MHV infection, as indicated by a pronounced reduction in plaque formation, nucleocapsid protein expression, and progeny production of MHV. Subsequently, a time-of-drug addition protocol, including pre-, co-, or post-treatment, was exploited to further evaluate the possible mechanism of antiviral activity mediated by strictinin, and remdesivir, a potential drug for the treatment of SARS-CoV-2, was used as a positive control against MHV infection. The results showed that all three treatments of remdesivir (20 μM) completely blocked MHV infection. In contrast, no significant effect on MHV infection was observed when cells were pre-treated with strictinin (100 μM) prior to infection, while significant inhibition of MHV infection was observed when strictinin was introduced upon viral adsorption (co-treatment) and after viral entry (post-treatment). Of note, as compared with the co-treatment group, the inhibitory effect of strictinin was more striking in the post-treatment group. These results indicate that strictinin suppresses MHV infection by multiple mechanisms; it possibly interferes with viral entry and also critical step(s) of viral infection. Evidently, strictinin significantly inhibited MHV infection and might be a suitable ingredient for protection against coronavirus infection.

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Murine Hepatitis Virus, a Biosafety Level 2 Model for SARS-CoV-2, Can Remain Viable on Meat and Meat Packaging Materials for at Least 48 Hours

Cited by 5 publications

References 54 publications

Retinoic Acid-Mediated Inhibition of Mouse Coronavirus Replication Is Dependent on IRF3 and CaMKK

Retinoic Acid-Mediated Inhibition of Mouse Coronavirus Replication Is Dependent on IRF3 and CaMKK

Antiviral Effect of Antimicrobial Peptoid TM9 and Murine Model of Respiratory Coronavirus Infection

Strictinin, a Major Ingredient in Yunnan Kucha Tea Possessing Inhibitory Activity on the Infection of Mouse Hepatitis Virus to Mouse L Cells

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