Dicer is involved in protection against influenza A virus infection

In mammals the interferon (IFN) system is a central innate antiviral defence mechanism, while the involvement of RNA interference (RNAi) in antiviral response against RNA viruses is uncertain. Here, we tested whether RNAi is involved in the antiviral response in mammalian cells. To investigate the role of RNAi in influenza A virus-infected cells in the absence of IFN, we used Vero cells that lack IFN-α and IFN-β genes. Our results demonstrate that knockdown of a key RNAi component, Dicer, led to a modest increase of virus production and accelerated apoptosis of influenza A virus-infected cells. These effects were much weaker in the presence of IFN. The results also show that in both Vero cells and the IFN-producing alveolar epithelial A549 cell line influenza A virus targets Dicer at mRNA and protein levels. Thus, RNAi is involved in antiviral response, and Dicer is important for protection against influenza A virus infection.

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Thapsigargin at Non-Cytotoxic Levels Induces a Potent Host Antiviral Response that Blocks Influenza A Virus Replication

Viruses ◽

10.3390/v12101093 ◽

2020 ◽

Vol 12 (10) ◽

pp. 1093

Author(s):

Leah V. Goulding ◽

Jiayun Yang ◽

Zhimin Jiang ◽

Hongyu Zhang ◽

Daniel Lea ◽

...

Keyword(s):

Virus Infection ◽

Influenza A Virus ◽

Influenza A ◽

Unmet Need ◽

Virus Production ◽

Antiviral Response ◽

Interferon Response ◽

Attractive Alternative ◽

Type I ◽

Host Antiviral Response

Influenza A virus is a major global pathogen of humans, and there is an unmet need for effective antivirals. Current antivirals against influenza A virus directly target the virus and are vulnerable to mutational resistance. Harnessing an effective host antiviral response is an attractive alternative. We show that brief exposure to low, non-toxic doses of thapsigargin (TG), an inhibitor of the sarcoplasmic/endoplasmic reticulum (ER) Ca2+ ATPase pump, promptly elicits an extended antiviral state that dramatically blocks influenza A virus production. Crucially, oral administration of TG protected mice against lethal virus infection and reduced virus titres in the lungs of treated mice. TG-induced ER stress unfolded protein response appears as a key driver responsible for activating a spectrum of host antiviral defences that include an enhanced type I/III interferon response. Our findings suggest that TG is potentially a viable host-centric antiviral for the treatment of influenza A virus infection without the inherent problem of drug resistance.

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Mucosal Reactive Oxygen Species Are Required for Antiviral Response: Role of Duox in Influenza A Virus Infection

Antioxidants and Redox Signaling ◽

10.1089/ars.2013.5353 ◽

2014 ◽

Vol 20 (17) ◽

pp. 2695-2709 ◽

Cited By ~ 57

Author(s):

Monika Strengert ◽

Richard Jennings ◽

Suzel Davanture ◽

Patti Hayes ◽

Gülsah Gabriel ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Virus Infection ◽

Influenza A Virus ◽

Influenza A ◽

Reactive Oxygen ◽

Antiviral Response ◽

Oxygen Species ◽

Influenza A Virus Infection

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Histone Deacetylase 6 Knockout Mice Exhibit Higher Susceptibility to Influenza A Virus Infection

Viruses ◽

10.3390/v12070728 ◽

2020 ◽

Vol 12 (7) ◽

pp. 728 ◽

Cited By ~ 2

Author(s):

Mark Zanin ◽

Jennifer DeBeauchamp ◽

Gowthami Vangala ◽

Richard J. Webby ◽

Matloob Husain

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Histone Deacetylase ◽

Influenza A Virus ◽

Influenza A ◽

Antiviral Response ◽

Histone Deacetylase 6 ◽

Influenza A Virus Infection ◽

Innate Antiviral Response ◽

Mouse Lungs

The host innate defence against influenza virus infection is an intricate system with a plethora of antiviral factors involved. We have identified host histone deacetylase 6 (HDAC6) as an anti-influenza virus factor in cultured cells. Consistent with this, we report herein that HDAC6 knockout (KO) mice are more susceptible to influenza virus A/PR/8/1934 (H1N1) infection than their wild type (WT) counterparts. The KO mice lost weight faster than the WT mice and, unlike WT mice, could not recover their original body weight. Consequently, more KO mice succumbed to infection, which corresponded with higher lung viral loads. Conversely, the expression of the critical innate antiviral response genes interferon alpha/beta, CD80, CXCL10 and IL15 was significantly downregulated in KO mouse lungs compared to WT mouse lungs. These data are consistent with the known function of HDAC6 of de-acetylating the retinoic acid inducible gene-I (RIG-I) and activating the host innate antiviral response cascade. Loss of HDAC6 thus leads to a blunted innate response and increased susceptibility of mice to influenza A virus infection.

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Proton Channel Activity of Influenza A Virus Matrix Protein 2 Contributes to Autophagy Arrest

Journal of Virology ◽

10.1128/jvi.00576-15 ◽

2015 ◽

Vol 90 (1) ◽

pp. 591-598 ◽

Cited By ~ 25

Author(s):

Yizhong Ren ◽

Chufang Li ◽

Liqiang Feng ◽

Weiqi Pan ◽

Liang Li ◽

...

Keyword(s):

Virus Infection ◽

Influenza A Virus ◽

Influenza A ◽

Matrix Protein ◽

Proton Channel ◽

Channel Activity ◽

Infected Cells ◽

Influenza A Virus Infection ◽

M2 Proton Channel

Influenza A virus infection can arrest autophagy, as evidenced by autophagosome accumulation in infected cells. Here, we report that this autophagosome accumulation can be inhibited by amantadine, an antiviral proton channel inhibitor, in amantadine-sensitive virus infected cells or cells expressing influenza A virus matrix protein 2 (M2). Thus, M2 proton channel activity plays a role in blocking the fusion of autophagosomes with lysosomes, which might be a key mechanism for arresting autophagy.

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