scholarly journals MicroRNA Involvement in Signaling Pathways During Viral Infection

2020 ◽  
Vol 8 ◽  
Author(s):  
Madalina Gabriela Barbu ◽  
Carmen Elena Condrat ◽  
Dana Claudia Thompson ◽  
Oana Larisa Bugnar ◽  
Dragos Cretoiu ◽  
...  
Keyword(s):  
Viral Infection ◽  
Signaling Pathways

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

2020 ◽  
Vol 94 (6) ◽  
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.

scholarly journals Penaeidins are a novel family of antiviral effectors against WSSV in shrimp

2018 ◽  
Author(s):  
Bang Xiao ◽  
Qihui Fu ◽  
Shengwen Niu ◽  
Haoyang Li ◽  
Kai Lǚ ◽  
...  
Keyword(s):  
Viral Infection ◽  
Signaling Pathways ◽  
Outer Surface ◽  
Phagocytic Activity ◽  
White Spot Syndrome Virus ◽  
Antiviral Immunity ◽  
White Spot ◽  
Structural Proteins ◽  
First Report ◽  
White Spot Syndrome

AbstractPenaeidins are members of a family of key effectors with broad anti-bacterial activities in penaeid shrimp. However, the function of penaeidins in antiviral immunity is rarely reported and remains largely unknown. Herein, we uncovered that penaeidins are a novel family of antiviral effectors against white spot syndrome virus (WSSV). Firstly, RNAi in vivo mediated knockdown of each penaeidin from four identified penaeidins from Litopenaeus vannamei resulted in elevated viral loads and rendered shrimp more susceptible to WSSV, whilst the phenotype of survival rate in penaeidin-silenced shrimp can be rescued via the injection of recombinant penaeidin proteins. Moreover, pull-down assays demonstrated the conserved PEN domain of penaeidin was able to interact with WSSV structural proteins. Furthermore, we observed that colloidal gold-labeled penaeidins were located on the outer surface of the WSSV virion. By infection-blocking assay, we observed that hemocytes had lower viral infection rates in the group of WSSV preincubated with penaeidins than those of control group. Phagocytic activity analysis further showed that penaeidins were able to inhibit phagocytic activity of hemocytes against WSSV Taken together, these results suggest that penaeidins specifically binds to WSSV virion by interacting with its structural proteins, thus preventing viral infection that confers host against WSSV. In addition, dual-luciferase assay and EMSA assay demonstrated that penaeidins were regulated by Dorsal and Relish, two transcription factors of the canonical Toll and IMD pathway, respectively. To our best knowledge, this is the first report on uncovering the antiviral function of penaeidins in the innate immune system of shrimp.ImportancesWhite spot syndrome, caused by white spot syndrome virus (WSSV), is the most serious disease in shrimp aquaculture, which has long been a scourge of cultured shrimp industry. Herein, we provided some substantial evidences to indicate that penaeidins are a novel family of effectors with antiviral activity against WSSV in shrimp. Penaeidins such as BigPEN, PEN2 and PEN3 were able to interact with the outer surface of WSSV virion via binding to viral structural proteins, and thus preventing viral entry host cells. In addition, we demonstrated that the Toll and IMD signaling pathways can regulate the transcriptional expression of penaeidins, which may suggest an important role of the conserved innate signaling pathways in antiviral immunity. This is the first report of the antiviral mechanism of penaeidins in shrimp, which may provide some new insights into strategies to control WSSV infection in shrimp farms.

scholarly journals Alteration in Cellular Signaling and Metabolic Reprogramming during Viral Infection

mBio ◽  
2021 ◽  
Author(s):  
Anil Pant ◽  
Lara Dsouza ◽  
Zhilong Yang
Keyword(s):  
Viral Infection ◽  
Signaling Pathways ◽  
Cellular Signaling ◽  
Metabolic Reprogramming ◽  
Obligate Intracellular ◽  
Intracellular Parasites

Cellular activities are finely regulated by numerous signaling pathways to support specific functions of complex life processes. Viruses are obligate intracellular parasites.

scholarly journals Quantitative measurement of activity of JAK-STAT signaling pathways in blood samples and immune cells to predict innate and adaptive cellular immune response to viral infection and accelerate vaccine development

2020 ◽  
Author(s):  
Wilbert Bouwman ◽  
Wim Verhaegh ◽  
Laurent Holtzer ◽  
Anja van de Stolpe
Keyword(s):  
Immune Response ◽  
Viral Infection ◽  
Signaling Pathways ◽  
Cellular Immune Response ◽  
Vaccine Development ◽  
Host Immune Response ◽  
Blood Samples ◽  
Pathway Activity ◽  
Adaptive Immune ◽  
Cellular Immune

AbstractThe host immune response determines the clinical course of a viral infection, for example in case of COVID-19 infection. The effectiveness of vaccination also depends on the induced immune response. Currently there is no method to measure the cellular immune response in blood samples. The functional activity of cells of innate and adaptive immune system is determined by coordinated activity of signaling pathways, especially the JAK-STAT pathways. Using a previously described approach we developed mRNA-based tests to measure activity of these signaling pathways, and show that they can be used to measure in a quantitative manner the cellular innate and adaptive immune response to a viral infection or vaccine in whole blood, PBMC, and specific immune cell type samples. Pathway activity level and range in healthy individuals was established, enabling interpretation of a pathway activity score on a patient sample without the need for a reference sample. Evidence is presented that the pathway activity analysis may also be useful for in vitro vaccine development and assessment of vaccine immunogenicity. Other envisioned applications lie in development of immunomodulatory drugs and drug response prediction and monitoring. Tests are expected to be of value in the COVID-19 crisis. In addition to the described Affymetrix microarray-based pathway tests for measuring host immune response, qPCR-based versions are in development; the latter can in principle be performed within three hours in routine hospital labs.

scholarly journals Hepatitis B Virus–Hepatocyte Interactions and Innate Immune Responses: Experimental Models and Molecular Mechanisms

2019 ◽  
Vol 39 (03) ◽  
pp. 301-314 ◽  
Author(s):  
Emmanuel Thomas ◽  
Thomas F. Baumert
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Immune Responses ◽  
Viral Infection ◽  
Signaling Pathways ◽  
Viral Pathogenesis ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Host Interactions ◽  
B Virus

AbstractChronic hepatitis B virus (HBV) infection is a major cause of liver disease and cancer worldwide. While current therapeutic approaches can efficiently control viral infection, efficient curative antivirals are absent. The understanding of virus–hepatocyte interactions and sensing of viral infection is an important prerequisite for the development of novel antiviral therapies for cure. Hepatocyte intrinsic innate immunity provides a rapid first line of defense to combat viral infection through the upregulation of antiviral and inflammatory genes. However, the functional relevance of many of these antiviral signaling pathways in the liver and their role in HBV pathogenesis is still only partially understood. The recent identification of intracellular RNA and DNA sensing pathways and their involvement in disease biology, including viral pathogenesis and carcinogenesis, is currently transforming our understanding of virus–host interactions. Here the authors review the current knowledge on intrinsic antiviral innate immune responses including the role of viral nucleic acid sensing pathways in the liver. Since HBV has been designated as a “stealth virus,” the study of the impact of HBV on signaling pathways in the hepatocyte is of significant interest to understand viral pathogenesis. Characterizing the mechanism underlying these HBV–host interactions and targeting related pathways to enhance antiviral innate responses may open new strategies to trigger noncytopathic clearance of covalently closed circular DNA to ultimately cure patients with chronic HBV infection.

scholarly journals Foot-and-Mouth Disease Virus Antagonizes NOD2-Mediated Antiviral Effects by Inhibiting NOD2 Protein Expression

2019 ◽  
Vol 93 (11) ◽  
Author(s):  
Huisheng Liu ◽  
Zixiang Zhu ◽  
Qiao Xue ◽  
Fan Yang ◽  
Weijun Cao ◽  
...  
Keyword(s):  
Amino Acids ◽  
Protein Expression ◽  
Viral Infection ◽  
Signaling Pathways ◽  
Foot And Mouth Disease ◽  
Protein Levels ◽  
Fmdv Infection ◽  
Mouth Disease Virus ◽  
Infected Cells ◽  
Fmdv Replication

ABSTRACT The role of nucleotide-binding oligomerization domain 2 (NOD2) in foot-and-mouth disease virus (FMDV)-infected cells remains unknown. Here, we showed that FMDV infection activated NOD2-mediated beta interferon (IFN-β) and nuclear factor-κB (NF-ĸB) signaling pathways. NOD2 inhibited FMDV replication in the infected cells. FMDV infection triggered NOD2 transcription, while it reduced the abundance of NOD2 protein. Our results revealed that FMDV 2B, 2C, and 3C proteinase (3Cpro) were responsible for the decrease in NOD2 protein levels. 3Cpro is a viral proteinase that can cleave multiple host proteins and limit protein synthesis. Our previous studies determined that FMDV 2B suppressed protein expression of RIG-I and LGP2. Here, we found that 3Cpro and 2B also decreased NOD2 expression. However, this is the first report that 2C induced the reduction of NOD2 protein levels. We determined that both 2B- and 2C-induced decreases in NOD2 were independent of the cleavage of host eukaryotic translation initiation factor 4 gamma (eIF4G), induction of cellular apoptosis, or proteasome, lysosome, and caspase pathways. The interactions between NOD2 and 2B or 2C were observed in the context of viral infection. The carboxyl-terminal amino acids 105 to 114 and 135 to 144 of 2B were essential for the reduction of NOD2, while the residues 105 to 114 were required for the interaction. Amino acids 116 to 260 of the carboxyl terminus of 2C were essential for the interaction, while truncated 2C mutants did not reduce NOD2. These data suggested novel antagonistic mechanisms of FMDV that were mediated by 2B, 2C, and 3Cpro proteins. IMPORTANCE NOD2 was identified as a cytoplasmic viral pattern recognition receptor in 2009. Subsequently, many viruses were reported to activate NOD2-mediated signaling pathways. This study demonstrated that FMDV infection activated NOD2-mediated IFN-β and NF-ĸB signaling pathways. Host cells have developed multiple strategies against viral infection; however, viruses have evolved many strategies to escape host defenses. FMDV has evolved multiple mechanisms to inhibit host type I IFN production. Here, we showed that NOD2 suppressed FMDV replication during viral infection. FMDV 2B, 2C, and 3Cpro decreased NOD2 protein expression by different mechanisms to promote viral replication. This study provided new insight into the immune evasion mechanisms mediated by FMDV and identified 2B, 2C, and 3Cpro as antagonistic factors for FMDV to evade host antiviral responses.

scholarly journals PABPC4 Broadly Inhibits Coronavirus Replication by Degrading Nucleocapsid Protein through Selective Autophagy

2021 ◽  
Author(s):  
Yajuan Jiao ◽  
Ning Kong ◽  
Hua Wang ◽  
Dage Sun ◽  
Sujie Dong ◽  
...  
Keyword(s):  
Viral Replication ◽  
Viral Infection ◽  
Signaling Pathways ◽  
Nucleocapsid Protein ◽  
Restriction Factors ◽  
Host Restriction ◽  
Selective Autophagy ◽  
Antiviral Responses ◽  
Host Restriction Factors

Emerging coronaviruses (CoVs) can cause severe diseases in humans and animals, but none of the currently available drugs or vaccines can effectively control these diseases. During viral infection, the host will activate the interferon (IFN) signaling pathways and host restriction factors in maintaining the innate antiviral responses and suppressing viral replication.

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