Type I Interferons: Distinct Biological Activities and Current Applications for Viral Infection

Li, Shifang; Gong, Mei-jiao; Zhao, Furong; Shao, Jing; Xie, Youming; Zhang, Yongguang; Chang, Huiyun

doi:10.1159/000495897

Cited by 141 publications

(122 citation statements)

References 153 publications

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“…Type I interferon (IFN-I) is a key component of the innate antiviral response, and constitutes the first line of host defence against influenza virus infection [41][42][43] . The activation of the IFN-I response requires PACT, which interacts with RNA polymerase, and nonstructural proteins NS1 and NS2 of influenza A virus 44 .…”

Section: Discussionmentioning

confidence: 99%

Antiviral activity of iridoid glycosides extracted from Fructus Gardeniae against influenza A virus by PACT-dependent suppression of viral RNA replication

Guo

Bao

et al. 2020

Sci Rep

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Epidemic and pandemic influenza A virus (IAV) poses a significant threat to human populations worldwide. Iridoid glycosides are principal bioactive components from the Gardenia jasminoides J. Ellis fruit that exhibit antiviral activity against several strains of IAV. In the present study, we evaluated the protective effect of Fructus Gardeniae iridoid glycoside extracts (IGEs) against IAV by cytopathogenic effect(CPE), MTT and a plaque formation assay in vitro and examined the reduction in the pulmonary index (PI), restoration of body weight, reduction in mortality and increases in survival time in vivo.As a host factor, PACT provides protection against the pathogenic influenza A virus by interacting with IAV polymerase and activating the IFN-I response. To verify the whether IGEs suppress IAV replication in a PACT-dependent manner, IAV RNA replication, expression of PACT and the phosphorylation of eIF2α in A549 cells were detected; the levels of IFNβ, PACT and PKR in mouse lung tissues were determined; and the activity of IAV polymerase was evaluated in PACT-compromised cells. The results indicated that IGEs sufficiently alleviated cell damage and suppressed IAV replication in vitro, protecting mice from IAV-induced injury and lethal IAV infection. These anti-IAV effects might be related to disrupted interplay between IVA polymerase and PACT and/or prevention of a PACT-dependent overactivated IFN-I antiviral response. Taken together, our findings reveal a new facet of the mechanisms by which IGEs fight the influenza A virus in a PACT-dependent manner.

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Section: Discussionmentioning

confidence: 99%

Antiviral activity of iridoid glycosides extracted from Fructus Gardeniae against influenza A virus by PACT-dependent suppression of viral RNA replication

Guo

Bao

et al. 2020

Sci Rep

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“…Upon infection, Influenza virus triggers the innate immune response in host cells to produce Type I interferons (IFNs), which in turn inhibit viral replication. Hence, IFN could be used as a therapy choice for influenza [22]. In our current work, IFNβ treatment activated ACE2 expression in primary human bronchial epithelial cells, suggesting that the host response of ACE2 upregulation is associated with the IFN signaling pathway.…”

Section: Discussionmentioning

confidence: 51%

Influenza Viral Infection is a High-Risk Factor for Developing Coronavirus Disease 2019 (COVID-19)

Zhang¹,

Zhang²

2020

Preprint

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Coronavirus disease 2019 (COVID-19) is caused by infection with the 2019 novel coronavirus 2 (2019-nCoV, now referred to as SARS-CoV-2). COVID-19 has become a global pandemic since its outbreak at the end of Dec 2019. COVID-19 could lead to severe acute respiratory disease, especially to those who have reduced immunity. Binding of the viral Spike protein (S) to its receptor ACE2 (Angiotensin Converting Enzyme 2) on the surface of target cells has been proven to be key for virus entry and infection. Although ACE2 expression in the respiratory system is necessary for pneumonia infection by SARS-CoV-2, the regulation of ACE2 gene expression remains poorly investigated, especially for patients that are in pre-pathological conditions. Here, by analyzing The Gene Expression Omnibus (GEO) database, we investigated the expression regulation of ACE2 in various kinds of primary epithelial cells from the respiratory system after influenza A or respiratory Syncytial Virus (RSV) infection. Our analyses reveal that infection of influenza A, RSV or influenza vaccines greatly increased ACE2 expression, suggesting that influenza viral infection could represent a high risk factor for developing COVID-19. We also found that the regulatory effect of influenza A virus on ACE2 expression is associated with activation of the interferon beta-induced pathway and viral RNA-activated host response. Together, our data provide a theoretical framework for clinical classification for SARS-CoV-2 infection susceptibility and could be used for future prevention and therapy treatment for COVID-19.

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“…Previous studies on the antiviral activity of lopinavir against MERS-CoV are conflicting with one study reporting micromolar EC 50 values in a human hepatoma cell line (Huh 7) yet another reported that lopinavir had no activity in a non-human primate kidney cell line (Vero) de Wilde et al, 2014). Type I interferons are approved for treating multiple indications including hepatitis B and C, and multiple sclerosis (Dumitrescu et al, 2018;Li et al, 2018). Two studies showed interferon-beta was effective against MERS-CoV infection in non-human primate kidney cells (Vero) with EC 50 values < 10 IU/mL Hart et al, 2014).…”

Section: Remdesivir Provides Superior Therapeutic Efficacy To Lopinavmentioning

confidence: 99%

Advances in respiratory virus therapeutics – A meeting report from the 6th isirv Antiviral Group conference

Nam²,

et al. 2019

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Type I Interferons: Distinct Biological Activities and Current Applications for Viral Infection

Cited by 141 publications

References 153 publications

Antiviral activity of iridoid glycosides extracted from Fructus Gardeniae against influenza A virus by PACT-dependent suppression of viral RNA replication

Antiviral activity of iridoid glycosides extracted from Fructus Gardeniae against influenza A virus by PACT-dependent suppression of viral RNA replication

Influenza Viral Infection is a High-Risk Factor for Developing Coronavirus Disease 2019 (COVID-19)

Advances in respiratory virus therapeutics – A meeting report from the 6th isirv Antiviral Group conference

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