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Article ; Online: Interferons in coronavirus pathogenesis: The good, the bad, and the ugly.

Channappanavar, Rudragouda

2022 Volume 30, Issue 4, Page(s) 427–430

Abstract: Interferons (IFNs) are a key component of the innate antiviral immunity and are generally implicated in protective host immune responses. Here, I discuss the central role of IFNs during different coronavirus (CoV) infections, the importance of timing of ... ...

Abstract	Interferons (IFNs) are a key component of the innate antiviral immunity and are generally implicated in protective host immune responses. Here, I discuss the central role of IFNs during different coronavirus (CoV) infections, the importance of timing of the IFN response, and how emerging human coronaviruses subvert antiviral IFN response to cause severe disease.
MeSH term(s)	Antiviral Agents/therapeutic use ; COVID-19 ; Cell Line ; Humans ; Immunity, Innate ; Interferons
Chemical Substances	Antiviral Agents ; Interferons (9008-11-1)
Language	English
Publishing date	2022-04-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	2278004-X
ISSN	1934-6069 ; 1931-3128
ISSN (online)	1934-6069
ISSN	1931-3128
DOI	10.1016/j.chom.2022.03.022
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Article ; Online: Alveolar macrophages protect mice from MERS-CoV-induced pneumonia and severe disease.

Channappanavar, Rudragouda / Selvaraj, Muneeswaran / More, Sunil / Perlman, Stanley

Veterinary pathology

2022 Volume 59, Issue 4, Page(s) 627–638

Abstract: Emerging and re-emerging human coronaviruses (hCoVs) cause severe respiratory illness in humans, but the basis for lethal pneumonia in these diseases is not well understood. Alveolar macrophages (AMs) are key orchestrators of host antiviral defense and ... ...

Abstract	Emerging and re-emerging human coronaviruses (hCoVs) cause severe respiratory illness in humans, but the basis for lethal pneumonia in these diseases is not well understood. Alveolar macrophages (AMs) are key orchestrators of host antiviral defense and tissue tolerance during a variety of respiratory infections, and AM dysfunction is associated with severe COVID-19. In this study, using a mouse model of Middle East respiratory syndrome coronavirus (MERS-CoV) infection, we examined the role of AMs in MERS pathogenesis. Our results show that depletion of AMs using clodronate (CL) liposomes significantly increased morbidity and mortality in human dipeptidyl peptidase 4 knock-in (hDPP4-KI) mice. Detailed examination of control and AM-depleted lungs at different days postinfection revealed increased neutrophil activity but a significantly reduced MERS-CoV-specific CD4 T-cell response in AM-deficient lungs during later stages of infection. Furthermore, enhanced MERS severity in AM-depleted mice correlated with lung inflammation and lesions. Collectively, these data demonstrate that AMs are critical for the development of an optimal virus-specific T-cell response and controlling excessive inflammation during MERS-CoV infection.
MeSH term(s)	Animals ; Clodronic Acid ; Coronavirus Infections/immunology ; Macrophages, Alveolar/immunology ; Mice ; Mice, Transgenic ; Middle East Respiratory Syndrome Coronavirus ; Pneumonia/immunology ; Pneumonia/virology
Chemical Substances	Clodronic Acid (0813BZ6866)
Language	English
Publishing date	2022-05-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	188012-3
ISSN	1544-2217 ; 0300-9858
ISSN (online)	1544-2217
ISSN	0300-9858
DOI	10.1177/03009858221095270
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Article: Alveolar macrophages protect mice from MERS-CoV-induced pneumonia and severe disease

Channappanavar, Rudragouda / Selvaraj, Muneeswaran / More, Sunil / Perlman, Stanley

Veterinary pathology. 2022 July, v. 59, no. 4

2022

Abstract	Emerging and re-emerging human coronaviruses (hCoVs) cause severe respiratory illness in humans, but the basis for lethal pneumonia in these diseases is not well understood. Alveolar macrophages (AMs) are key orchestrators of host antiviral defense and tissue tolerance during a variety of respiratory infections, and AM dysfunction is associated with severe COVID-19. In this study, using a mouse model of Middle East respiratory syndrome coronavirus (MERS-CoV) infection, we examined the role of AMs in MERS pathogenesis. Our results show that depletion of AMs using clodronate (CL) liposomes significantly increased morbidity and mortality in human dipeptidyl peptidase 4 knock-in (hDPP4-KI) mice. Detailed examination of control and AM-depleted lungs at different days postinfection revealed increased neutrophil activity but a significantly reduced MERS-CoV-specific CD4 T-cell response in AM-deficient lungs during later stages of infection. Furthermore, enhanced MERS severity in AM-depleted mice correlated with lung inflammation and lesions. Collectively, these data demonstrate that AMs are critical for the development of an optimal virus-specific T-cell response and controlling excessive inflammation during MERS-CoV infection.
Keywords	CD4-positive T-lymphocytes ; COVID-19 infection ; Middle East respiratory syndrome coronavirus ; animal pathology ; disease severity ; humans ; inflammation ; lungs ; macrophages ; mice ; morbidity ; mortality ; neutrophils ; pathogenesis ; pneumonia
Language	English
Dates of publication	2022-07
Size	p. 627-638.
Publishing place	SAGE Publications
Document type	Article
ZDB-ID	188012-3
ISSN	1544-2217 ; 0300-9858
ISSN (online)	1544-2217
ISSN	0300-9858
DOI	10.1177/03009858221095270
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Age-related susceptibility to coronavirus infections: role of impaired and dysregulated host immunity.

Channappanavar, Rudragouda / Perlman, Stanley

The Journal of clinical investigation

2020 Volume 130, Issue 12, Page(s) 6204–6213

Abstract: Human coronaviruses (hCoVs) cause severe respiratory illness in the elderly. Age-related impairments in innate immunity and suboptimal virus-specific T cell and antibody responses are believed to cause severe disease upon respiratory virus infections. ... ...

Abstract	Human coronaviruses (hCoVs) cause severe respiratory illness in the elderly. Age-related impairments in innate immunity and suboptimal virus-specific T cell and antibody responses are believed to cause severe disease upon respiratory virus infections. This phenomenon has recently received increased attention, as elderly patients are at substantially elevated risk for severe COVID-19 disease and experience increased rates of mortality following SARS-CoV-2 infection compared with younger populations. However, the basis for age-related fatal pneumonia following pathogenic hCoVs is not well understood. In this Review, we provide an overview of our current understanding of hCoV-induced fatal pneumonia in the elderly. We describe host immune response to hCoV infections derived from studies of young and aged animal models and discuss the potential role of age-associated increases in sterile inflammation (inflammaging) and virus-induced dysregulated inflammation in causing age-related severe disease. We also highlight the existing gaps in our knowledge about virus replication and host immune responses to hCoV infection in young and aged individuals.
MeSH term(s)	Aging/immunology ; Animals ; COVID-19/immunology ; Disease Models, Animal ; Disease Susceptibility ; Humans ; Immunity, Innate ; Inflammation/immunology ; Inflammation/virology ; Risk Factors ; SARS-CoV-2/immunology ; Severity of Illness Index
Keywords	covid19
Language	English
Publishing date	2020-10-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI144115
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Article ; Online: Evaluation of Activation and Inflammatory Activity of Myeloid Cells During Pathogenic Human Coronavirus Infection.

Channappanavar, Rudragouda / Perlman, Stanley

Methods in molecular biology (Clifton, N.J.)

2020 Volume 2099, Page(s) 195–204

Abstract: Innate immune cells play a vital role in mounting an effective host response to a variety of pathogen challenges. Myeloid cells such as neutrophils and monocyte-macrophages are major innate leukocytes that orchestrate protective immunity to viral lung ... ...

Abstract	Innate immune cells play a vital role in mounting an effective host response to a variety of pathogen challenges. Myeloid cells such as neutrophils and monocyte-macrophages are major innate leukocytes that orchestrate protective immunity to viral lung infections. However, a dysregulated cytokine response can promote excessive infiltration and robust pro-inflammatory activity of neutrophils and monocyte-macrophages, leading to fatal disease. Following virus infection, the beneficial or deleterious role of infiltrating neutrophils and monocyte-macrophages is determined largely by their ability to secrete inflammatory cytokines and chemokines. A majority of studies use the total number of infiltrating cells and their activation status as measures to demonstrate their role during an infection. Consequently, the ability of neutrophils and Inflammatory Monocyte Macrophages (IMMs) to secrete inflammatory cytokines and chemokines, and its correlation with the disease severity, is not well defined. In this chapter, we report useful markers to identify lung infiltrating innate immune cells and define their activation status. We also describe a simple method to measure intracellular cytokine production to evaluate the inflammatory activity of neutrophils and IMMs in a mouse model of human coronavirus infection.
MeSH term(s)	Animals ; Chemokines/immunology ; Coronavirus Infections/immunology ; Coronavirus Infections/virology ; Cytokines/immunology ; Disease Models, Animal ; Humans ; Immunity, Innate ; Inflammation/immunology ; Leukocytes/immunology ; Lung/immunology ; Macrophages/immunology ; Mice ; Mice, Inbred BALB C ; Middle East Respiratory Syndrome Coronavirus/immunology ; Monocytes/immunology ; Myeloid Cells/immunology ; Neutrophils/immunology ; SARS Virus/immunology
Chemical Substances	Chemokines ; Cytokines
Keywords	covid19
Language	English
Publishing date	2020-01-09
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-0211-9_15
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Klebsiella pneumoniae C

Villalva, Crystal / Patil, Girish / Narayanan, Sai / Chanda, Debarati / Ghimire, Roshan / Snider, Timothy / Ramachandran, Akhilesh / Channappanavar, Rudragouda / More, Sunil

bioRxiv : the preprint server for biology

2023

Abstract: SARS-CoV-2 patients have been reported to have high rates of ... ...

Abstract	SARS-CoV-2 patients have been reported to have high rates of secondary
Language	English
Publishing date	2023-08-01
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.07.28.551035
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Acellular Human Amniotic Fluid-Derived Extracellular Vesicles as Novel Anti-Inflammatory Therapeutics against SARS-CoV-2 Infection.

Chanda, Debarati / Del Rivero, Tania / Ghimire, Roshan / More, Sunil / Mitrani, Maria Ines / Bellio, Michael A / Channappanavar, Rudragouda

Viruses

2024 Volume 16, Issue 2

Abstract: The ongoing COVID-19 pandemic caused by SARS-CoV-2 is associated with acute respiratory distress syndrome (ARDS) and fatal pneumonia. Excessive inflammation caused by SARS-CoV-2 is the key driver of ARDS and lethal disease. Several FDA-approved drugs ... ...

Abstract	The ongoing COVID-19 pandemic caused by SARS-CoV-2 is associated with acute respiratory distress syndrome (ARDS) and fatal pneumonia. Excessive inflammation caused by SARS-CoV-2 is the key driver of ARDS and lethal disease. Several FDA-approved drugs that suppress virus replication are in clinical use. However, despite strong evidence for the role of virus-induced inflammation in severe COVID-19, no effective anti-inflammatory drug is available to control fatal inflammation as well as efficiently clear the virus. Therefore, there is an urgent need to identify biologically derived immunomodulators that suppress inflammation and promote antiviral immunity. In this study, we evaluated acellular human amniotic fluid (acAF) containing extracellular vesicles (hAF-EVs) as a potential non-toxic and safe biologic for immunomodulation during COVID-19. Our in vitro results showed that acAF significantly reduced inflammatory cytokine production in TLR2/4/7 and SARS-CoV-2 structural protein-stimulated mouse macrophages. Importantly, an intraperitoneal administration of acAF reduced morbidity and mortality in SARS-CoV-2-infected mice. A detailed examination of SARS-CoV-2-infected lungs revealed that the increased protection in acAF-treated mice was associated with reduced viral titers and levels of inflammatory myeloid cell infiltration. Collectively, our results identify a novel biologic that has potential to suppress excessive inflammation and enhance survival following SARS-CoV-2 infection, highlighting the translational potential of acAF against COVID-19.
MeSH term(s)	Humans ; Animals ; Mice ; COVID-19 ; SARS-CoV-2 ; Amniotic Fluid ; Pandemics ; Inflammation ; Respiratory Distress Syndrome ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/therapeutic use ; Extracellular Vesicles ; Biological Products
Chemical Substances	Anti-Inflammatory Agents ; Biological Products
Language	English
Publishing date	2024-02-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v16020273
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Toll-like receptor 7 (TLR7)-mediated antiviral response protects mice from lethal SARS-CoV-2 infection.

Ghimire, Roshan / Shrestha, Rakshya / Amaradhi, Radhika / Patton, Titus / Whitley, Cody / Chanda, Debarati / Liu, Lin / Ganesh, Thota / More, Sunil / Channappanavar, Rudragouda

bioRxiv : the preprint server for biology

2023

Abstract: SARS-CoV-2-induced impaired antiviral and excessive inflammatory responses cause fatal pneumonia. However, the key pattern recognition receptors that elicit effective antiviral and lethal inflammatory ... ...

Abstract	SARS-CoV-2-induced impaired antiviral and excessive inflammatory responses cause fatal pneumonia. However, the key pattern recognition receptors that elicit effective antiviral and lethal inflammatory responses
Language	English
Publishing date	2023-05-09
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.05.08.539929
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Coronaviruses: Innate Immunity, Inflammasome Activation, Inflammatory Cell Death, and Cytokines.

Lee, SangJoon / Channappanavar, Rudragouda / Kanneganti, Thirumala-Devi

Trends in immunology

2020 Volume 41, Issue 12, Page(s) 1083–1099

Abstract: The innate immune system acts as the first line of defense against pathogens, including coronaviruses (CoVs). Severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV are epidemic zoonotic CoVs that emerged at the ... ...

Abstract	The innate immune system acts as the first line of defense against pathogens, including coronaviruses (CoVs). Severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV are epidemic zoonotic CoVs that emerged at the beginning of the 21st century. The recently emerged virus SARS-CoV-2 is a novel strain of CoV that has caused the coronavirus 2019 (COVID-19) pandemic. Scientific advancements made by studying the SARS-CoV and MERS-CoV outbreaks have provided a foundation for understanding pathogenesis and innate immunity against SARS-CoV-2. In this review, we focus on our present understanding of innate immune responses, inflammasome activation, inflammatory cell death pathways, and cytokine secretion during SARS-CoV, MERS-CoV, and SARS-CoV-2 infection. We also discuss how the pathogenesis of these viruses influences these biological processes.
MeSH term(s)	Animals ; COVID-19/immunology ; Cell Death/immunology ; Cytokines/immunology ; Humans ; Immunity, Innate/immunology ; Inflammasomes/immunology ; SARS-CoV-2/immunology
Chemical Substances	Cytokines ; Inflammasomes
Keywords	covid19
Language	English
Publishing date	2020-10-15
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2036831-8
ISSN	1471-4981 ; 1471-4906
ISSN (online)	1471-4981
ISSN	1471-4906
DOI	10.1016/j.it.2020.10.005
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Zs.A 1601: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Age-related susceptibility to coronavirus infections: role of impaired and dysregulated host immunity

Channappanavar, Rudragouda / Perlman, Stanley

J. clin. invest

Abstract	Human coronaviruses (hCoVs) cause severe respiratory illness in the elderly. Age-related impairments in innate immunity and suboptimal virus-specific T cell and antibody responses are believed to cause severe disease upon respiratory virus infections. This phenomenon has recently received increased attention, as elderly patients are at substantially elevated risk for severe COVID-19 disease and experience increased rates of mortality following SARS-CoV-2 infection compared with younger populations. However, the basis for age-related fatal pneumonia following pathogenic hCoVs is not well understood. In this Review, we provide an overview of our current understanding of hCoV-induced fatal pneumonia in the elderly. We describe host immune response to hCoV infections derived from studies of young and aged animal models and discuss the potential role of age-associated increases in sterile inflammation (inflammaging) and virus-induced dysregulated inflammation in causing age-related severe disease. We also highlight the existing gaps in our knowledge about virus replication and host immune responses to hCoV infection in young and aged individuals.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #883460
Database	COVID19

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