scholarly journals Chicken DNA Sensing cGAS-STING Signal Pathway Mediates Broad Spectrum Antiviral Functions

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 369
Author(s):  
Shuangjie Li ◽  
Jie Yang ◽  
Yuanyuan Zhu ◽  
Xingyu Ji ◽  
Kun Wang ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Innate Immunity ◽  
Viral Infections ◽  
Rna Viruses ◽  
Signal Pathway ◽  
Synergistic Activity ◽  
Dna Sensors ◽  
Dna Sensing ◽  
Dna Viruses ◽  
Antiviral Effects

The innate DNA sensing receptors are one family of pattern recognition receptors and play important roles in antiviral infections, especially DNA viral infections. Among the multiple DNA sensors, cGAS has been studied intensively and is most defined in mammals. However, DNA sensors in chickens have not been much studied, and the chicken cGAS is still not fully understood. In this study, we investigated the chicken cGAS-STING signal axis, revealed its synergistic activity, species-specificity, and the signal essential sites in cGAS. Importantly, both cGAS and STING exhibited antiviral effects against DNA viruses, retroviruses, and RNA viruses, suggesting the broad range antiviral functions and the critical roles in chicken innate immunity.

scholarly journals Double-Stranded RNA Is Produced by Positive-Strand RNA Viruses and DNA Viruses but Not in Detectable Amounts by Negative-Strand RNA Viruses

2006 ◽  
Vol 80 (10) ◽  
pp. 5059-5064 ◽  
Author(s):  
Friedemann Weber ◽  
Valentina Wagner ◽  
Simon B. Rasmussen ◽  
Rune Hartmann ◽  
Søren R. Paludan
Keyword(s):  
Viral Infections ◽  
Rna Viruses ◽  
Innate Immune ◽  
Genome Replication ◽  
Dna Viruses ◽  
Double Stranded Rna ◽  
Positive Strand ◽  
Negative Strand ◽  
A Genome ◽  
Positive Strand Rna

ABSTRACT Double-stranded RNA (dsRNA) longer than 30 bp is a key activator of the innate immune response against viral infections. It is widely assumed that the generation of dsRNA during genome replication is a trait shared by all viruses. However, to our knowledge, no study exists in which the production of dsRNA by different viruses is systematically investigated. Here, we investigated the presence and localization of dsRNA in cells infected with a range of viruses, employing a dsRNA-specific antibody for immunofluorescence analysis. Our data revealed that, as predicted, significant amounts of dsRNA can be detected for viruses with a genome consisting of positive-strand RNA, dsRNA, or DNA. Surprisingly, however, no dsRNA signals were detected for negative-strand RNA viruses. Thus, dsRNA is indeed a general feature of most virus groups, but negative-strand RNA viruses appear to be an exception to that rule.

scholarly journals Herpes Simplex Virus 1 Ubiquitin-Specific Protease UL36 Abrogates NF-κB Activation in DNA Sensing Signal Pathway

2016 ◽  
Vol 91 (5) ◽  
Author(s):  
Ruijie Ye ◽  
Chenhe Su ◽  
Haiyan Xu ◽  
Chunfu Zheng
Keyword(s):  
Innate Immunity ◽  
Signal Pathway ◽  
Innate Immune ◽  
Dna Sensing ◽  
Herpes Simplex Virus 1 ◽  
Polyubiquitin Chains ◽  
Specific Protease ◽  
Ubiquitin Specific Protease ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT The DNA sensing pathway triggers innate immune responses against DNA virus infection, and NF-κB signaling plays a critical role in establishing innate immunity. We report here that the herpes simplex virus 1 (HSV-1) ubiquitin-specific protease (UL36USP), which is a deubiquitinase (DUB), antagonizes NF-κB activation, depending on its DUB activity. In this study, ectopically expressed UL36USP blocked promoter activation of beta interferon (IFN-β) and NF-κB induced by cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING). UL36USP restricted NF-κB activation mediated by overexpression of STING, TANK-binding kinase 1, IκB kinase α (IKKα), and IKKβ, but not p65. UL36USP was also shown to inhibit IFN-stimulatory DNA-induced IFN-β and NF-κB activation under conditions of HSV-1 infection. Furthermore, UL36USP was demonstrated to deubiquitinate IκBα and restrict its degradation and, finally, abrogate NF-κB activation. More importantly, the recombinant HSV-1 lacking UL36USP DUB activity, denoted as C40A mutant HSV-1, failed to cleave polyubiquitin chains on IκBα. For the first time, UL36USP was shown to dampen NF-κB activation in the DNA sensing signal pathway to evade host antiviral innate immunity. IMPORTANCE It has been reported that double-stranded-DNA-mediated NF-κB activation is critical for host antiviral responses. Viruses have established various strategies to evade the innate immune system. The N terminus of the HSV-1 UL36 gene-encoded protein contains the DUB domain and is conserved across all herpesviruses. This study demonstrates that UL36USP abrogates NF-κB activation by cleaving polyubiquitin chains from IκBα and therefore restricts proteasome-dependent degradation of IκBα and that DUB activity is indispensable for this process. This study expands our understanding of the mechanisms utilized by HSV-1 to evade the host antiviral innate immune defense induced by NF-κB signaling.

scholarly journals The Antiviral Effects of Na,K-ATPase Inhibition: A Minireview

2018 ◽  
Vol 19 (8) ◽  
pp. 2154 ◽  
Author(s):  
Luciano Amarelle ◽  
Emilia Lecuona
Keyword(s):  
Cardiac Glycosides ◽  
Viral Infections ◽  
Biological Processes ◽  
Host Proteins ◽  
Dna Viruses ◽  
Promising Strategy ◽  
Antiviral Effects ◽  
Intracellular Signal ◽  
Syncytial Virus ◽  
Atpase Inhibition

Since being first described more than 60 years ago, Na,K-ATPase has been extensively studied, while novel concepts about its structure, physiology, and biological roles continue to be elucidated. Cardiac glycosides not only inhibit the pump function of Na,K-ATPase but also activate intracellular signal transduction pathways, which are important in many biological processes. Recently, antiviral effects have been described as a novel feature of Na,K-ATPase inhibition with the use of cardiac glycosides. Cardiac glycosides have been reported to be effective against both DNA viruses such as cytomegalovirus and herpes simplex and RNA viruses such as influenza, chikungunya, coronavirus, and respiratory syncytial virus, among others. Consequently, cardiac glycosides have emerged as potential broad-spectrum antiviral drugs, with the great advantage of targeting cell host proteins, which help to minimize resistance to antiviral treatments, making them a very promising strategy against human viral infections. Here, we review the effect of cardiac glycosides on viral biology and the mechanisms by which these drugs impair the replication of this array of different viruses.

scholarly journals The Roles of Host 5-Methylcytosine RNA Methyltransferases during Viral Infections

2020 ◽  
Vol 21 (21) ◽  
pp. 8176
Author(s):  
Maciej Wnuk ◽  
Piotr Slipek ◽  
Mateusz Dziedzic ◽  
Anna Lewinska
Keyword(s):  
Innate Immunity ◽  
Dna Methyltransferase ◽  
Viral Infections ◽  
Rna Viruses ◽  
Host Responses ◽  
Rna Sequences ◽  
Methyl Group ◽  
Trna Methyltransferase ◽  
Host Innate Immunity ◽  
Sun Domain

Eukaryotic 5-methylcytosine RNA methyltransferases catalyze the transfer of a methyl group to the fifth carbon of a cytosine base in RNA sequences to produce 5-methylcytosine (m5C). m5C RNA methyltransferases play a crucial role in the maintenance of functionality and stability of RNA. Viruses have developed a number of strategies to suppress host innate immunity and ensure efficient transcription and translation for the replication of new virions. One such viral strategy is to use host m5C RNA methyltransferases to modify viral RNA and thus to affect antiviral host responses. Here, we summarize the latest findings concerning the roles of m5C RNA methyltransferases, namely, NOL1/NOP2/SUN domain (NSUN) proteins and DNA methyltransferase 2/tRNA methyltransferase 1 (DNMT2/TRDMT1) during viral infections. Moreover, the use of m5C RNA methyltransferase inhibitors as an antiviral therapy is discussed.

Oncogenesis and the Lucké Virus

1968 ◽  
Vol 26 ◽  
pp. 200-201
Author(s):  
A. E. Vatter ◽  
J. Zambernard
Keyword(s):  
Rna Viruses ◽  
Vegetative State ◽  
Temperature Sensitive ◽  
Structural Level ◽  
Oncogenic Viruses ◽  
Dna Viruses ◽  
Leopard Frogs ◽  
Renal Adenocarcinoma ◽  
Induced Tumors ◽  
Northern Leopard Frogs

Oncogenic viruses, like viruses in general, can be divided into two classes, those that contain deoxyribonucleic acid (DNA) and those that contain ribonucleic acid (RNA). The RNA viruses have been recovered readily from the tumors which they cause whereas, the DNA-virus induced tumors have not yielded the virus. Since DNA viruses cannot be recovered, the bulk of present day investigations have been concerned with RNA viruses.The Lucké renal adenocarcinoma is a spontaneous tumor which occurs in northern leopard frogs (Rana pipiens) and has received increased attention in recent years because of its probable viral etiology. This hypothesis was first advanced by Lucké after he observed intranuclear inclusions in some of the tumor cells. Tumors with inclusions were examined at the fine structural level by Fawcett who showed that they contained immature and mature virus˗like particles.The use of this system in the study of oncogenic tumors offers several unique features, the virus has been shown to contain DNA and it can be recovered from the tumor, also, it is temperature sensitive. This latter feature is of importance because the virus can be transformed from a latent to a vegetative state by lowering or elevating the environmental temperature.

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