Faculty Opinions recommendation of Persistent activation of an innate immune response translates respiratory viral infection into chronic lung disease.

Host cells sense viral infection through pattern recognition receptors (PRRs), which detect pathogen-associated molecular patterns (PAMPs) and stimulate an innate immune response. PRRs are localized to several different cellular compartments and are stimulated by viral proteins and nucleic acids. PRR activation initiates signal transduction events that ultimately result in an inflammatory response. Human tumour viruses, which include Kaposi's sarcoma-associated herpesvirus, Epstein–Barr virus, human papillomavirus, hepatitis C virus, hepatitis B virus, human T-cell lymphotropic virus type 1 and Merkel cell polyomavirus, are detected by several different PRRs. These viruses engage in a variety of mechanisms to evade the innate immune response, including downregulating PRRs, inhibiting PRR signalling, and disrupting the activation of transcription factors critical for mediating the inflammatory response, among others. This review will describe tumour virus PAMPs and the PRRs responsible for detecting viral infection, PRR signalling pathways, and the mechanisms by which tumour viruses evade the host innate immune system. This article is part of the themed issue ‘Human oncogenic viruses’.

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Activation Of The Lung Innate Immune Response By Saccharopolyspora Rectivirgula Protects Against A Viral Infection In Mice

10.1164/ajrccm-conference.2010.181.1_meetingabstracts.a1804 ◽

2010 ◽

Author(s):

Melissa Girard ◽

Evelyne Israël-Assayag ◽

Yvon Cormier

Keyword(s):

Immune Response ◽

Viral Infection ◽

Innate Immune Response ◽

Innate Immune ◽

Saccharopolyspora Rectivirgula

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Interferon-Stimulated Genes as Enhancers of Antiviral Innate Immune Signaling

Journal of Innate Immunity ◽

10.1159/000484258 ◽

2017 ◽

Vol 10 (2) ◽

pp. 85-93 ◽

Cited By ~ 28

Author(s):

Keaton M. Crosse ◽

Ebony A. Monson ◽

Michael R. Beard ◽

Karla J. Helbig

Keyword(s):

Immune Response ◽

Viral Infection ◽

Innate Immune Response ◽

Innate Immune ◽

Regulatory Factor ◽

Interferon Stimulated Genes ◽

Innate Immune Signaling ◽

Recent Advancement ◽

Antiviral Function

The ability of a host to curb a viral infection is heavily reliant on the effectiveness of an initial antiviral innate immune response, resulting in the upregulation of interferon (IFN) and, subsequently, IFN-stimulated genes (ISGs). ISGs serve to mount an antiviral state within a host cell, and although the specific antiviral function of a number of ISGs has been characterized, the function of many of these ISGs remains to be determined. Recent research has uncovered a novel role for a handful of ISGs, some of them directly induced by IFN regulatory factor 3 in the absence of IFN itself. These ISGs, most with potent antiviral activity, are also able to augment varying arms of the innate immune response to viral infection, thereby strengthening this response. This new understanding of the role of ISGs may, in turn, help the recent advancement of novel therapeutics aiming to augment innate signaling pathways in an attempt to control viral infection and pathogenesis.

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Relative Contributions of the cGAS-STING and TLR3 Signaling Pathways to Attenuation of Herpes Simplex Virus 1 Replication

Journal of Virology ◽

10.1128/jvi.01717-19 ◽

2020 ◽

Vol 94 (6) ◽

Cited By ~ 1

Author(s):

Muhammad Bilal Latif ◽

Rameez Raja ◽

Patricia M. Kessler ◽

Ganes C. Sen

Keyword(s):

Immune Response ◽

Viral Infection ◽

Signaling Pathways ◽

Cell Lines ◽

Innate Immune Response ◽

Human Cell ◽

Innate Immune ◽

Human Cell Lines ◽

Herpes Simplex Virus 1 ◽

Hsv 1

ABSTRACT The innate immune response is crucial for defense against viral infections. Cells recognize virus infection through pattern recognition receptors and induce type I interferons as well as proinflammatory cytokines to orchestrate an innate immune response. Herpes simplex virus 1 (HSV-1) triggers both the cyclic GMP-AMP synthase (cGAS)–stimulator of interferon genes (STING) and Toll-like receptor 3 (TLR3) pathways. It is well known that TLR3 uses the adaptor protein Toll/interleukin-1 receptor (IL-1R) domain-containing adaptor-inducing beta interferon (TRIF) for signaling, but we recently reported that STING signaling also requires TRIF. Because STING directly binds to TRIF, we identified the STING-interacting domain of TRIF and generated STING-noninteracting mutants of human and mouse TRIFs. The mutant TRIFs were unable to support STING signaling, although they were fully functional in the TLR3 pathway. These mutants were used to assess the relative contributions of the TLR3 and STING pathways to the attenuation of HSV-1 replication in mouse and human cell lines. For this purpose, the mouse L929 and NB41A3 cell lines and the human HT1080 and HeLa-M cell lines, in which both the TLR3 and the STING pathways are operational, were used. The TRIF gene was disrupted in these lines by CRISPR/Cas9, before reconstituting them with mutant and wild-type TRIF expression vectors. Infection of the reconstituted cells with HSV-1 revealed that both the cGAS-STING and the TLR3 signaling pathways are required for the attenuation of virus replication, but their relative contributions in attenuating HSV-1 replication were found to be different in mouse versus human cell lines. Thus, our study suggests that the relative contributions of the cGAS-STING and the TLR3 pathways in the attenuation of viral infection may be species specific. IMPORTANCE The magnitude of fatal infections caused by all different viruses in human and animal populations justifies a better understanding of the host innate immune response process that attenuates virus replication. In particular, the relative contributions of different signaling pathways which are responsible for the generation of the innate immune response are still largely unknown. In this study, we used STING-noninteracting TRIF mutants to decipher the relative contributions of the TLR3 and cGAS-STING signaling pathways to the attenuation of HSV-1 infection. We show that the relative contributions of the two pathways to the attenuation of viral infection are different in mouse versus human cell lines. Together, our results provide new insights into the relative contributions of two different signaling pathways in the attenuation of viral infection and may lead to the development of new antiviral strategies aimed at blocking viral infection at very early stages.

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miR-26a Inhibits Feline Herpesvirus 1 Replication by Targeting SOCS5 and Promoting Type I Interferon Signaling

Viruses ◽

10.3390/v12010002 ◽

2019 ◽

Vol 12 (1) ◽

pp. 2 ◽

Cited By ~ 3

Author(s):

Jikai Zhang ◽

Zhijie Li ◽

Jiapei Huang ◽

Hang Yin ◽

Jin Tian ◽

...

Keyword(s):

Immune Response ◽

Viral Infection ◽

Innate Immune Response ◽

Antiviral Response ◽

Innate Immune ◽

Host Cells ◽

Type I ◽

Type I Ifn ◽

Feline Herpesvirus ◽

Herpesvirus 1

In response to viral infection, host cells activate various antiviral responses to inhibit virus replication. While feline herpesvirus 1 (FHV-1) manipulates the host early innate immune response in many different ways, the host could activate the antiviral response to counteract it through some unknown mechanisms. MicroRNAs (miRNAs) which serve as a class of regulatory factors in the host, participate in the regulation of the host innate immune response against virus infection. In this study, we found that the expression levels of miR-26a were significantly upregulated upon FHV-1 infection. Furthermore, FHV-1 infection induced the expression of miR-26a via a cGAS-dependent pathway, and knockdown of cellular cGAS significantly blocked the expression of miR-26a induced by poly (dA:dT) or FHV-1 infection. Next, we investigated the biological function of miR-26a during viral infection. miR-26a was able to increase the phosphorylation of STAT1 and promote type I IFN signaling, thus inhibiting viral replication. The mechanism study showed that miR-26a directly targeted host SOCS5. Knockdown of SOCS5 increased the phosphorylation of STAT1 and enhanced the type I IFN-mediated antiviral response, and overexpression of suppressor of the cytokine signalling 5 (SOCS5) decreased the phosphorylation of STAT1 and inhibited the type I IFN-mediated antiviral response. Meanwhile, with the knockdown of SOCS5, the upregulated expression of phosphorylated STAT1 and the anti-virus effect induced by miR-26a were significantly inhibited. Taken together, our data demonstrated a new strategy of host miRNAs against FHV-1 infection by enhancing IFN antiviral signaling.

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