scholarly journals Evasion of Antiviral Innate Immunity by Porcine Reproductive and Respiratory Syndrome Virus

2021 ◽  
Vol 12 ◽  
Author(s):  
Tong-Yun Wang ◽  
Ming-Xia Sun ◽  
Hong-Liang Zhang ◽  
Gang Wang ◽  
Guoqing Zhan ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Immune Responses ◽  
Viral Infections ◽  
Respiratory Syndrome Virus ◽  
Type I ◽  
Swine Industry ◽  
Interferon Stimulated Genes ◽  
Β Receptor ◽  
Underlying Mechanisms ◽  
Antiviral Innate Immunity

Innate immunity is the front line for antiviral immune responses and bridges adaptive immunity against viral infections. However, various viruses have evolved many strategies to evade host innate immunity. A typical virus is the porcine reproductive and respiratory syndrome virus (PRRSV), one of the most globally devastating viruses threatening the swine industry worldwide. PRRSV engages several strategies to evade the porcine innate immune responses. This review focus on the underlying mechanisms employed by PRRSV to evade pattern recognition receptors signaling pathways, type I interferon (IFN-α/β) receptor (IFNAR)-JAK-STAT signaling pathway, and interferon-stimulated genes. Deciphering the antiviral immune evasion mechanisms by PRRSV will enhance our understanding of PRRSV’s pathogenesis and help us to develop more effective methods to control and eliminate PRRSV.

scholarly journals Interplay between Intrinsic and Innate Immunity during HIV Infection

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 922 ◽  
Author(s):  
Louis Bergantz ◽  
Frédéric Subra ◽  
Eric Deprez ◽  
Olivier Delelis ◽  
Clémence Richetta
Keyword(s):  
Innate Immunity ◽  
Immune Responses ◽  
Hiv Infection ◽  
Type I ◽  
Restriction Factors ◽  
Intrinsic Immunity ◽  
First Line ◽  
Hiv Replication ◽  
Interferon Stimulated Genes ◽  
Immunodeficiency Virus

Restriction factors are antiviral components of intrinsic immunity which constitute a first line of defense by blocking different steps of the human immunodeficiency virus (HIV) replication cycle. In immune cells, HIV infection is also sensed by several pattern recognition receptors (PRRs), leading to type I interferon (IFN-I) and inflammatory cytokines production that upregulate antiviral interferon-stimulated genes (ISGs). Several studies suggest a link between these two types of immunity. Indeed, restriction factors, that are generally interferon-inducible, are able to modulate immune responses. This review highlights recent knowledge of the interplay between restriction factors and immunity inducing antiviral defenses. Counteraction of this intrinsic and innate immunity by HIV viral proteins will also be discussed.

scholarly journals When human guanylate-binding proteins meet viral infections

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Rongzhao Zhang ◽  
Zhixin Li ◽  
Yan-Dong Tang ◽  
Chenhe Su ◽  
Chunfu Zheng
Keyword(s):  
Innate Immunity ◽  
Viral Infection ◽  
Binding Proteins ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Innate Immune ◽  
Type I Interferons ◽  
Type I ◽  
Downstream Signaling ◽  
Antiviral Innate Immunity

AbstractInnate immunity is the first line of host defense against viral infection. After invading into the cells, pathogen-associated-molecular-patterns derived from viruses are recognized by pattern recognition receptors to activate the downstream signaling pathways to induce the production of type I interferons (IFN-I) and inflammatory cytokines, which play critical functions in the host antiviral innate immune responses. Guanylate-binding proteins (GBPs) are IFN-inducible antiviral effectors belonging to the guanosine triphosphatases family. In addition to exerting direct antiviral functions against certain viruses, a few GBPs also exhibit regulatory roles on the host antiviral innate immunity. However, our understanding of the underlying molecular mechanisms of GBPs' roles in viral infection and host antiviral innate immune signaling is still very limited. Therefore, here we present an updated overview of the functions of GBPs during viral infection and in antiviral innate immunity, and highlight discrepancies in reported findings and current challenges for future studies, which will advance our understanding of the functions of GBPs and provide a scientific and theoretical basis for the regulation of antiviral innate immunity.

The transmembrane serine protease hepsin suppresses type I interferon induction by cleaving STING

2021 ◽  
Vol 14 (687) ◽  
pp. eabb4752
Author(s):  
Fu Hsin ◽  
Yu-Chen Hsu ◽  
Yu-Fei Tsai ◽  
Shu-Wha Lin ◽  
Helene Minyi Liu
Keyword(s):  
Innate Immunity ◽  
Viral Infections ◽  
Ectopic Expression ◽  
Type I ◽  
Adapter Proteins ◽  
Type I Ifn ◽  
Chronic Viral Infections ◽  
Viral Proteases ◽  
Transmembrane Serine Protease ◽  
Antiviral Innate Immunity

Many viral proteases mediate the evasion of antiviral innate immunity by cleaving adapter proteins in the interferon (IFN) induction pathway. Host proteases are also involved in innate immunity and inflammation. Here, we report that the transmembrane protease hepsin (also known as TMPRSS1), which is predominantly present in hepatocytes, inhibited the induction of type I IFN during viral infections. Knocking out hepsin in mouse embryonic fibroblasts (MEFs) increased the viral infection–induced expression of Ifnb1, an Ifnb1 promoter reporter, and an IFN-sensitive response element promoter reporter. Ectopic expression of hepsin in cultured human hepatocytes and HEK293T cells suppressed the induction of IFNβ during viral infections by reducing the abundance of STING. These effects depended on the protease activity of hepsin. We identified a putative hepsin target site in STING and showed that mutating this site protected STING from hepsin-mediated cleavage. In addition to hepatocytes, several hepsin-producing prostate cancer cell lines showed reduced STING-mediated type I IFN induction and responses. These results reveal a role for hepsin in suppressing STING-mediated type I IFN induction, which may contribute to the vulnerability of hepatocytes to chronic viral infections.

scholarly journals Untangling the roles of RNA helicases in antiviral innate immunity

2021 ◽  
Vol 17 (12) ◽  
pp. e1010072
Author(s):  
Morgane Baldaccini ◽  
Sébastien Pfeffer
Keyword(s):  
Innate Immunity ◽  
Viral Infections ◽  
Current Knowledge ◽  
Rnai Pathway ◽  
Special Focus ◽  
Type I ◽  
Small Interfering Rnas ◽  
Rna Helicases ◽  
Viral Dsrna ◽  
Antiviral Innate Immunity

One of the first layers of protection that metazoans put in place to defend themselves against viruses rely on the use of proteins containing DExD/H-box helicase domains. These members of the duplex RNA–activated ATPase (DRA) family act as sensors of double-stranded RNA (dsRNA) molecules, a universal marker of viral infections. DRAs can be classified into 2 subgroups based on their mode of action: They can either act directly on the dsRNA, or they can trigger a signaling cascade. In the first group, the type III ribonuclease Dicer plays a key role to activate the antiviral RNA interference (RNAi) pathway by cleaving the viral dsRNA into small interfering RNAs (siRNAs). This represents the main innate antiviral immune mechanism in arthropods and nematodes. Even though Dicer is present and functional in mammals, the second group of DRAs, containing the RIG-I-like RNA helicases, appears to have functionally replaced RNAi and activate type I interferon (IFN) response upon dsRNA sensing. However, recent findings tend to blur the frontier between these 2 mechanisms, thereby highlighting the crucial and diverse roles played by RNA helicases in antiviral innate immunity. Here, we will review our current knowledge of the importance of these key proteins in viral infection, with a special focus on the interplay between the 2 main types of response that are activated by dsRNA.

scholarly journals Interaction between innate immunity and porcine reproductive and respiratory syndrome virus

2011 ◽  
Vol 12 (2) ◽  
pp. 149-167 ◽  
Author(s):  
Yongming Sang ◽  
Raymond R. R. Rowland ◽  
Frank Blecha
Keyword(s):  
Innate Immunity ◽  
Immune Responses ◽  
Immune Surveillance ◽  
Innate Immune ◽  
Respiratory Syndrome Virus ◽  
Virus Infections ◽  
Metabolic Factors ◽  
Chronic Infections ◽  
Swine Industry ◽  
Animal Virus

AbstractInnate immunity provides frontline antiviral protection and bridges adaptive immunity against virus infections. However, viruses can evade innate immune surveillance potentially causing chronic infections that may lead to pandemic diseases. Porcine reproductive and respiratory syndrome virus (PRRSV) is an example of an animal virus that has developed diverse mechanisms to evade porcine antiviral immune responses. Two decades after its discovery, PRRSV is still one of the most globally devastating viruses threatening the swine industry. In this review, we discuss the molecular and cellular composition of the mammalian innate antiviral immune system with emphasis on the porcine system. In particular, we focus on the interaction between PRRSV and porcine innate immunity at cellular and molecular levels. Strategies for targeting innate immune components and other host metabolic factors to induce ideal anti-PRRSV protection are also discussed.

scholarly journals Porcine Reproductive and Respiratory Syndrome Virus Evades Antiviral Innate Immunity via MicroRNAs Regulation

2021 ◽  
Vol 12 ◽  
Author(s):  
Xuan Zhang ◽  
Wen-Hai Feng
Keyword(s):  
Innate Immunity ◽  
Immune Evasion ◽  
Economic Losses ◽  
Respiratory Syndrome Virus ◽  
Swine Industry ◽  
Gene Expressions ◽  
Non Coding Rnas ◽  
New Treatments ◽  
Antiviral Innate Immunity

Porcine reproductive and respiratory syndrome (PRRS) is one of the most important diseases in pigs, leading to significant economic losses in the swine industry worldwide. MicroRNAs (miRNAs) are small single-stranded non-coding RNAs involved in regulating gene expressions at the post-transcriptional levels. A variety of host miRNAs are dysregulated and exploited by PRRSV to escape host antiviral surveillance and help virus infection. In addition, PRRSV might encode miRNAs. In this review, we will summarize current progress on how PRRSV utilizes miRNAs for immune evasions. Increasing knowledge of the role of miRNAs in immune evasion will improve our understanding of PRRSV pathogenesis and help us develop new treatments for PRRSV-associated diseases.

scholarly journals Single-nucleotide methylation specifically represses type I interferon in antiviral innate immunity

2021 ◽  
Vol 218 (3) ◽  
Author(s):  
Zheng-jun Gao ◽  
Wen-ping Li ◽  
Xin-tao Mao ◽  
Tao Huang ◽  
Hao-li Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Innate Immunity ◽  
Viral Infections ◽  
Critical Role ◽  
Endogenous Retrovirus ◽  
Type I ◽  
Single Nucleotide ◽  
Antiviral Immune Response ◽  
Genome Bisulfite Sequencing ◽  
Antiviral Innate Immunity

Frequent outbreaks of viruses have caused a serious threat to public health. Previous evidence has revealed that DNA methylation is correlated with viral infections, but its role in innate immunity remains poorly investigated. Additionally, DNA methylation inhibitors promote IFN-I by upregulating endogenous retrovirus; however, studies of intrinsically demethylated tumors do not support this conclusion. This study found that Uhrf1 deficiency in myeloid cells significantly upregulated Ifnb expression, increasing resistance to viral infection. We performed whole-genome bisulfite sequencing and found that a single-nucleotide methylation site in the Ifnb promoter region disrupted IRF3 recruitment. We used site-specific mutant knock-in mice and a region-specific demethylation tool to confirm that this methylated site plays a critical role in regulating Ifnb expression and antiviral responses. These findings provide essential insight into DNA methylation in the regulation of the innate antiviral immune response.

scholarly journals Immunological Aspects Related to Viral Infections in Severe Asthma and the Role of Omalizumab

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 348
Author(s):  
Francesco Menzella ◽  
Giulia Ghidoni ◽  
Carla Galeone ◽  
Silvia Capobelli ◽  
Chiara Scelfo ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Severe Asthma ◽  
Viral Infections ◽  
Respiratory Infections ◽  
Antiviral Effect ◽  
Point Of View ◽  
Type I ◽  
Effector Cells ◽  
Viral Spread ◽  
Increased Risk

Viral respiratory infections are recognized risk factors for the loss of control of allergic asthma and the induction of exacerbations, both in adults and children. Severe asthma is more susceptible to virus-induced asthma exacerbations, especially in the presence of high IgE levels. In the course of immune responses to viruses, an initial activation of innate immunity typically occurs and the production of type I and III interferons is essential in the control of viral spread. However, the Th2 inflammatory environment still appears to be protective against viral infections in general and in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections as well. As for now, literature data, although extremely limited and preliminary, show that severe asthma patients treated with biologics don’t have an increased risk of SARS-CoV-2 infection or progression to severe forms compared to the non-asthmatic population. Omalizumab, an anti-IgE monoclonal antibody, exerts a profound cellular effect, which can stabilize the effector cells, and is becoming much more efficient from the point of view of innate immunity in contrasting respiratory viral infections. In addition to the antiviral effect, clinical efficacy and safety of this biological allow a great improvement in the management of asthma.

scholarly journals Role of Alternative Splicing in Regulating Host Response to Viral Infection

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1720
Author(s):  
Kuo-Chieh Liao ◽  
Mariano A. Garcia-Blanco
Keyword(s):  
Innate Immunity ◽  
Alternative Splicing ◽  
Immune Responses ◽  
Viral Infection ◽  
Rna Splicing ◽  
Type I ◽  
Host Immune Responses ◽  
Transcriptional Regulatory Mechanisms ◽  
Host Virus Interactions

The importance of transcriptional regulation of host genes in innate immunity against viral infection has been widely recognized. More recently, post-transcriptional regulatory mechanisms have gained appreciation as an additional and important layer of regulation to fine-tune host immune responses. Here, we review the functional significance of alternative splicing in innate immune responses to viral infection. We describe how several central components of the Type I and III interferon pathways encode spliced isoforms to regulate IFN activation and function. Additionally, the functional roles of splicing factors and modulators in antiviral immunity are discussed. Lastly, we discuss how cell death pathways are regulated by alternative splicing as well as the potential role of this regulation on host immunity and viral infection. Altogether, these studies highlight the importance of RNA splicing in regulating host–virus interactions and suggest a role in downregulating antiviral innate immunity; this may be critical to prevent pathological inflammation.

scholarly journals β-Catenin Is Required for the cGAS/STING Signaling Pathway but Antagonized by the Herpes Simplex Virus 1 US3 Protein

2019 ◽  
Vol 94 (5) ◽  
Author(s):  
Hongjuan You ◽  
Yingying Lin ◽  
Feng Lin ◽  
Mingyue Yang ◽  
Jiahui Li ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Herpes Simplex ◽  
Immune Responses ◽  
Signaling Pathway ◽  
Kinase Activity ◽  
Dna Virus ◽  
Host Immune Responses ◽  
Simplex Virus ◽  
Antiviral Innate Immunity ◽  
Hsv 1

ABSTRACT The cGAS/STING-mediated DNA-sensing signaling pathway is crucial for interferon (IFN) production and host antiviral responses. Herpes simplex virus I (HSV-1) is a DNA virus that has evolved multiple strategies to evade host immune responses. Here, we demonstrate that the highly conserved β-catenin protein in the Wnt signaling pathway is an important factor to enhance the transcription of type I interferon (IFN-I) in the cGAS/STING signaling pathway, and the production of IFN-I mediated by β-catenin was antagonized by HSV-1 US3 protein via its kinase activity. Infection by US3-deficienct HSV-1 and its kinase-dead variants failed to downregulate IFN-I and IFN-stimulated gene (ISG) production induced by β-catenin. Consistent with this, absence of β-catenin enhanced the replication of US3-deficienct HSV-1, but not wild-type HSV-1. The underlying mechanism was the interaction of US3 with β-catenin and its hyperphosphorylation of β-catenin at Thr556 to block its nuclear translocation. For the first time, HSV-1 US3 has been shown to inhibit IFN-I production through hyperphosphorylation of β-catenin and to subvert host antiviral innate immunity. IMPORTANCE Although increasing evidence has demonstrated that HSV-1 subverts host immune responses and establishes lifelong latent infection, the molecular mechanisms by which HSV-1 interrupts antiviral innate immunity, especially the cGAS/STING-mediated cellular DNA-sensing signaling pathway, have not been fully explored. Here, we show that β-catenin promotes cGAS/STING-mediated activation of the IFN pathway, which is important for cellular innate immune responses and intrinsic resistance to DNA virus infection. The protein kinase US3 antagonizes the production of IFN by targeting β-catenin via its kinase activity. The findings in this study reveal a novel mechanism for HSV-1 to evade host antiviral immunity and add new knowledge to help in understanding the interaction between the host and HSV-1 infection.

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