Interferon-Lambda Intranasal Protection and Differential Sex Pathology in a Murine Model of SARS-CoV-2 Infection

Sohn, Sook-Young; Hearing, Janet; Mugavero, JoAnn; Kirillov, Varvara; Gorbunova, Elena E.; Helminiak, Luke; Mishra, Smruti; Mackow, Erich R.; Hearing, Patrick; Reich, Nancy C.; Kim, Hwan Keun

doi:10.1128/mbio.02756-21

Cited by 26 publications

(18 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Paralleling the potential, IFN-λ 1/3 has also been induced in early phases of infection and in convalescent COVID-19 patients ( 227 ). The results indicated that IFN-β and IFN-λ1 could block virus infection and inhibit the production of SARS-CoV-2 ( 226 , 228 ). In addition, the dysregulated production of type I IFNs and the exacerbated release of proinflammatory cytokines makes COVID-19 more severe ( 226 , 229 ).…”

Section: Cytokine Secretion Induced By Sars-cov-2 Infectionmentioning

confidence: 99%

The Role of Cytokines and Chemokines in Severe Acute Respiratory Syndrome Coronavirus 2 Infections

Hsu

Peng

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in countless infections and caused millions of deaths since its emergence in 2019. Coronavirus disease 2019 (COVID-19)-associated mortality is caused by uncontrolled inflammation, aberrant immune response, cytokine storm, and an imbalanced hyperactive immune system. The cytokine storm further results in multiple organ failure and lung immunopathology. Therefore, any potential treatments should focus on the direct elimination of viral particles, prevention strategies, and mitigation of the imbalanced (hyperactive) immune system. This review focuses on cytokine secretions of innate and adaptive immune responses against COVID-19, including interleukins, interferons, tumor necrosis factor-alpha, and other chemokines. In addition to the review focus, we discuss potential immunotherapeutic approaches based on relevant pathophysiological features, the systemic immune response against SARS-CoV-2, and data from recent clinical trials and experiments on the COVID-19-associated cytokine storm. Prompt use of these cytokines as diagnostic markers and aggressive prevention and management of the cytokine storm can help determine COVID-19-associated morbidity and mortality. The prophylaxis and rapid management of the cytokine storm appear to significantly improve disease outcomes. For these reasons, this study aims to provide advanced information to facilitate innovative strategies to survive in the COVID-19 pandemic.

show abstract

Section: Cytokine Secretion Induced By Sars-cov-2 Infectionmentioning

confidence: 99%

The Role of Cytokines and Chemokines in Severe Acute Respiratory Syndrome Coronavirus 2 Infections

Hsu

Peng

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…In contrast, IFN-III has been shown to limit viral activities at the local level without being associated with inflammation [118][119][120], conversely restricting the neutrophil inflammatory functions then limiting tissue damage [120][121][122]. In the context of SARS-CoV-2 infection, in vitro and in vivo studies have demonstrated antiviral IFN-III activities in epithelial cells without excessive inflammation [89,91,92,123,124]. Furthermore, the protein expression of IFN-λ2/λ3 were reduced in nasopharyngeal swab samples from COVID-19-positive individuals [125].…”

Section: Ifn-λmentioning

confidence: 99%

Characterization of SARS-CoV-2 Evasion: Interferon Pathway and Therapeutic Options

Znaidia

Demeret

Werf

et al. 2022

Viruses

View full text Add to dashboard Cite

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic. SARS-CoV-2 is characterized by an important capacity to circumvent the innate immune response. The early interferon (IFN) response is necessary to establish a robust antiviral state. However, this response is weak and delayed in COVID-19 patients, along with massive pro-inflammatory cytokine production. This dysregulated innate immune response contributes to pathogenicity and in some individuals leads to a critical state. Characterizing the interplay between viral factors and host innate immunity is crucial to better understand how to manage the disease. Moreover, the constant emergence of new SARS-CoV-2 variants challenges the efficacy of existing vaccines. Thus, to control this virus and readjust the antiviral therapy currently used to treat COVID-19, studies should constantly be re-evaluated to further decipher the mechanisms leading to SARS-CoV-2 pathogenesis. Regarding the role of the IFN response in SARS-CoV-2 infection, in this review we summarize the mechanisms by which SARS-CoV-2 evades innate immune recognition. More specifically, we explain how this virus inhibits IFN signaling pathways (IFN-I/IFN-III) and controls interferon-stimulated gene (ISG) expression. We also discuss the development and use of IFNs and potential drugs controlling the innate immune response to SARS-CoV-2, helping to clear the infection.

show abstract

“…Thus, while IFN-l expression appears to correlate inversely with COVID-19 severity, its mechanism(s) of protection is not well understood. Although IFN-l has been studied in animals in the context of SARS-CoV-2 infection (Boudewijns et al, 2020;Broggi et al, 2020a;Dinnon et al, 2020;Sohn et al, 2021) and has been postulated to have a protective antiviral role, the responding cell types and targets of action have not been identified.…”

Section: Introductionmentioning

confidence: 99%

Nasally delivered interferon-λ protects mice against infection by SARS-CoV-2 variants including Omicron

et al. 2022

View full text Add to dashboard Cite

Interferon-Lambda Intranasal Protection and Differential Sex Pathology in a Murine Model of SARS-CoV-2 Infection

Abstract: The COVID-19 pandemic has claimed millions of lives worldwide. In this report, we used a preclinical mouse model to investigate the prophylactic and therapeutic value of intranasal IFN-λ for this acute respiratory disease.

Cited by 26 publications

References 43 publications

The Role of Cytokines and Chemokines in Severe Acute Respiratory Syndrome Coronavirus 2 Infections

The Role of Cytokines and Chemokines in Severe Acute Respiratory Syndrome Coronavirus 2 Infections

Characterization of SARS-CoV-2 Evasion: Interferon Pathway and Therapeutic Options

Nasally delivered interferon-λ protects mice against infection by SARS-CoV-2 variants including Omicron

Contact Info

Product

Resources

About