scholarly journals Recombinant Human Thymosin Beta-4 Protects against Mouse Coronavirus Infection

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Rui Yu ◽  
Yunyun Mao ◽  
Kai Li ◽  
Yanfang Zhai ◽  
Yue Zhang ◽  
...  
Keyword(s):  
Actin Polymerization ◽  
Hepatitis Virus ◽  
Mouse Hepatitis Virus ◽  
Ideal Model ◽  
Highly Pathogenic ◽  
Thymosin Beta 4 ◽  
N Terminus ◽  
Coronavirus Infection ◽  
Level 2 ◽  
Biosafety Level

Coronaviruses (CoVs) are enveloped and harbor an unusually large (30–32 kb) positive-strand linear RNA genome. Highly pathogenic coronaviruses cause severe acute respiratory syndrome (SARS) (SARS-CoV and SARS-CoV-2) and Middle East respiratory syndrome (MERS) (MERS-CoV) in humans. The coronavirus mouse hepatitis virus (MHV) infects mice and serves as an ideal model of viral pathogenesis, mainly because experiments can be conducted using animal-biosafety level-2 (A-BSL2) containment. Human thymosin beta-4 (Tβ4), a 43-residue peptide with an acetylated N-terminus, is widely expressed in human tissues. Tβ4 regulates actin polymerization and functions as an anti-inflammatory molecule and an antioxidant as well as a promoter of wound healing and angiogenesis. These activities led us to test whether Tβ4 serves to treat coronavirus infections of humans. To test this possibility, here, we established a BALB/c mouse model of coronavirus infection using mouse CoV MHV-A59 to evaluate the potential protective effect of recombinant human Tβ4 (rhTβ4). Such a system can be employed under A-BSL2 containment instead of A-BSL3 that is required to study coronaviruses infectious for humans. We found that rhTβ4 significantly increased the survival rate of mice infected with MHV-A59 through inhibiting virus replication, balancing the host’s immune response, alleviating pathological damage, and promoting repair of the liver. These results will serve as the basis for further application of rhTβ4 to the treatment of human CoV diseases such as COVID-19.

scholarly journals Murine Coronavirus Infection Activates the Aryl Hydrocarbon Receptor in an Indoleamine 2,3-Dioxygenase-Independent Manner, Contributing to Cytokine Modulation and Proviral TCDD-Inducible-PARP Expression

2019 ◽  
Vol 94 (3) ◽  
Author(s):  
Matthew E. Grunewald ◽  
Mohamed G. Shaban ◽  
Samantha R. Mackin ◽  
Anthony R. Fehr ◽  
Stanley Perlman
Keyword(s):  
Immune Response ◽  
Viral Replication ◽  
Aryl Hydrocarbon Receptor ◽  
Hepatitis Virus ◽  
Mouse Hepatitis Virus ◽  
Host Immune Response ◽  
Indoleamine 2,3 Dioxygenase ◽  
Aryl Hydrocarbon ◽  
Coronavirus Infection ◽  
In Cells

ABSTRACT The aryl hydrocarbon receptor (AhR) is a cytoplasmic receptor/transcription factor that modulates several cellular and immunological processes following activation by pathogen-associated stimuli, though its role during virus infection is largely unknown. Here, we show that AhR is activated in cells infected with mouse hepatitis virus (MHV), a coronavirus (CoV), and contributes to the upregulation of downstream effector TCDD-inducible poly(ADP-ribose) polymerase (TiPARP) during infection. Knockdown of TiPARP reduced viral replication and increased interferon expression, suggesting that TiPARP functions in a proviral manner during MHV infection. We also show that MHV replication induced the expression of other genes known to be downstream of AhR in macrophages and dendritic cells and in livers of infected mice. Further, we found that chemically inhibiting or activating AhR reciprocally modulated the expression levels of cytokines induced by infection, specifically, interleukin 1β (IL-1β), IL-10, and tumor necrosis factor alpha (TNF-α), consistent with a role for AhR activation in the host response to MHV infection. Furthermore, while indoleamine 2,3-dioxygenase (IDO1) drives AhR activation in other settings, MHV infection induced equal expression of downstream genes in wild-type (WT) and IDO1−/− macrophages, suggesting an alternative pathway of AhR activation. In summary, we show that coronaviruses elicit AhR activation by an IDO1-independent pathway, contributing to upregulation of downstream effectors, including the proviral factor TiPARP, and to modulation of cytokine gene expression, and we identify a previously unappreciated role for AhR signaling in CoV pathogenesis. IMPORTANCE Coronaviruses are a family of positive-sense RNA viruses with human and agricultural significance. Characterizing the mechanisms by which coronavirus infection dictates pathogenesis or counters the host immune response would provide targets for the development of therapeutics. Here, we show that the aryl hydrocarbon receptor (AhR) is activated in cells infected with a prototypic coronavirus, mouse hepatitis virus (MHV), resulting in the expression of several effector genes. AhR is important for modulation of the host immune response to MHV and plays a role in the expression of TiPARP, which we show is required for maximal viral replication. Taken together, our findings highlight a previously unidentified role for AhR in regulating coronavirus replication and the immune response to the virus.

scholarly journals Ketogenic diet restrains aging-induced exacerbation of coronavirus infection in mice

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Seungjin Ryu ◽  
Irina Shchukina ◽  
Yun-Hee Youm ◽  
Hua Qing ◽  
Brandon Hilliard ◽  
...  
Keyword(s):  
T Cells ◽  
Ketogenic Diet ◽  
Hepatitis Virus ◽  
Influenza Infection ◽  
Immune Surveillance ◽  
Mouse Hepatitis Virus ◽  
Γδ T Cells ◽  
Aged Mice ◽  
Inflammatory Damage ◽  
Coronavirus Infection

Increasing age is the strongest predictor of risk of COVID-19 severity and mortality. Immunometabolic switch from glycolysis to ketolysis protects against inflammatory damage and influenza infection in adults. To investigate how age compromises defense against coronavirus infection, and whether a pro-longevity ketogenic-diet (KD) impacts immune-surveillance, we developed an aging model of natural murine beta coronavirus (mCoV) infection with mouse hepatitis virus strain-A59 (MHV-A59). When inoculated intranasally, mCoV is pneumotropic and recapitulates several clinical hallmarks of COVID-19 infection. Aged mCoV-A59-infected mice have increased mortality and higher systemic inflammation in the heart, adipose tissue and hypothalamus, including neutrophilia and loss of γδ T cells in lungs. Activation of ketogenesis in aged mice expands tissue protective γδ T cells, deactivates the NLRP3 inflammasome and decreases pathogenic monocytes in lungs of infected aged mice. These data establish harnessing of the ketogenic immunometabolic checkpoint as a potential treatment against coronavirus infection in the aged.

scholarly journals Production of Pseudotyped Particles to Study Highly Pathogenic Coronaviruses in a Biosafety Level 2 Setting

10.3791/59010 ◽  
2019 ◽  
Author(s):  
Jean K. Millet ◽  
Tiffany Tang ◽  
Lakshmi Nathan ◽  
Javier A. Jaimes ◽  
Hung-Lun Hsu ◽  
...  
Keyword(s):  
Highly Pathogenic ◽  
Level 2 ◽  
Biosafety Level ◽  
Biosafety Level 2

scholarly journals Optimized Protocols for the Propagation and Quantification of Infectious Murine Hepatitis Virus (MHV-A59) Using NCTC Clone 1469 and 929 Cells

2022 ◽  
Vol 5 (1) ◽  
pp. 5
Author(s):  
Tautvydas Shuipys ◽  
Naim Montazeri
Keyword(s):  
Cell Lines ◽  
Hepatitis Virus ◽  
Plaque Assay ◽  
Culture Collection ◽  
Murine Hepatitis Virus ◽  
Virus Particles ◽  
Pathogenic Viruses ◽  
Overlay Assay ◽  
Level 2 ◽  
Biosafety Level

Murine hepatitis virus (MHV) is a non-human pathogen betacoronavirus that is evolutionarily and structurally related to the human pathogenic viruses SARS-CoV, MERS-CoV, and SARS-CoV-2. However, unlike the human SARS and MERS viruses, MHV requires a biosafety level 2 laboratory for propagating and safe handling, making it a potentially suitable surrogate virus. Despite this utility, few papers discussed the propagation and quantification of MHV using cell lines readily available in biorepositories making their implementations not easily reproducible. This article provides protocols for propagating and quantifying MHV-A59 using the recommended NCTC clone 1469 and clone 929 cell lines from American Type Culture Collection (ATCC). More specifically, the methods detail reviving cells, routine cell passaging, preparing freeze stocks, infection of NCTC clone 1469 with MHV and subsequent harvesting, and plaque assay quantification of MHV using NCTC clone 929 cells. Using these protocols, a BSL-2 laboratory equipped for cell culture work would generate at least 6.0 log plaque-forming units (PFU) per mL of MHV lysate and provide an optimized overlay assay using either methylcellulose or agarose as overlays for the titration of infectious virus particles. The protocols described here are intended to be utilized for persistence and inactivation studies of coronaviruses.

scholarly journals A biosafety level 2 surrogate for studying SARS-CoV-2 survival in food processing environmental biofilms

2021 ◽  
Author(s):  
Austin Blake Featherstone ◽  
Sapna Chitlapilly Dass
Keyword(s):  
Hepatitis Virus ◽  
Fold Increase ◽  
Meat Processing ◽  
Mixed Species ◽  
Murine Hepatitis Virus ◽  
Viral Particles ◽  
Processing Facility ◽  
Processing Plants ◽  
Level 2 ◽  
Biosafety Level

Meat processing plants have been at the center of the SARS-CoV-2 pandemic. There are several factors that contribute to the persistence of SARS-CoV-2 in meat processing plants and one of the factors is the formation of a multi-species biofilm with virus. Biofilm can act as a reservoir in protecting, harboring, and dispersing SARS-CoV-2 from biofilm to the meat processing facility environment. We used Murine Hepatitis Virus (MHV) as a surrogate for SARS-CoV-2 virus and meat processing facility drain samples to develop mixed-species biofilms on commonly found materials in processing facilities (Stainless-Steel (SS), PVC and tiles). The results showed that MHV was able to integrate into the environmental biofilm and survived for a period of 5 days at 7C. There was no significate difference between the viral-environmental biofilm biovolumes developed on different materials SS, PVC, and tiles. There was a 2-fold increase in the virus-environmental biofilm biovolume when compared to environmental biofilm by itself. These results indicate a complex virus-environmental biofilm interaction which is providing enhanced protection for the survival of viral particles with the environmental biofilm community.

Mouse Hepatitis Virus Infection Suppresses Modulation of Mouse Spleen T- Cell Activation

1988 ◽  
Author(s):  
Joan M. Cook-Mills ◽  
Hidayatulla G. Munshi ◽  
Robert L. Perlman ◽  
Donald A. Chambers
Keyword(s):  
T Cell ◽  
Virus Infection ◽  
T Cell Activation ◽  
Cell Activation ◽  
Hepatitis Virus ◽  
Mouse Hepatitis Virus ◽  
Mouse Spleen ◽  
Hepatitis Virus Infection

scholarly journals Effect of persistent mouse hepatitis virus infection on MHC Class I expression in murine astrocytes

1995 ◽  
Vol 40 (1) ◽  
pp. 10-21 ◽  
Author(s):  
J. Correale ◽  
S. Li ◽  
L. P. Weiner ◽  
Wendy Gilmore
Keyword(s):  
Virus Infection ◽  
Mhc Class I ◽  
Hepatitis Virus ◽  
Mouse Hepatitis Virus ◽  
Class I ◽  
Hepatitis Virus Infection

scholarly journals SARS-CoV-2 vs. Hepatitis Virus Infection Risk in the Hemodialysis Population: What Should We Expect?

2021 ◽  
Vol 18 (11) ◽  
pp. 5748
Author(s):  
Luis D’Marco ◽  
María Jesús Puchades ◽  
Miguel Ángel Serra ◽  
Lorena Gandía ◽  
Sergio Romero-Alcaide ◽  
...  
Keyword(s):  
Hepatitis Virus ◽  
Contact Precaution ◽  
Hepatitis Viruses ◽  
International Consensus ◽  
Infection Treatment ◽  
High Incidence ◽  
Dramatic Rise ◽  
Infection Disease ◽  
Coronavirus Infection ◽  
Hepatitis Virus Infection

Since the dramatic rise of the coronavirus infection disease 2019 (COVID-19) pandemic, patients receiving dialysis have emerged as especially susceptible to this infection because of their impaired immunologic state, chronic inflammation and the high incidence of comorbidities. Although several strategies have thus been implemented to minimize the risk of transmission and acquisition in this population worldwide, the reported severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence varies across studies but is higher than in the general population. On the contrary, the screening for hepatitis viruses (HBV and HCV) has seen significant improvements in recent years, with vaccination in the case of HBV and effective viral infection treatment for HCV. In this sense, a universal SARS-CoV-2 screening and contact precaution appear to be effective in preventing further transmission. Finally, regarding the progress, an international consensus with updated protocols that prioritize between old and new indicators would seem a reasonable tool to address these unexpended changes for the nephrology community.

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