Paramyxovirus and other RNA virus infections

RNA virus infections can lead to the onset of severe diseases such as fever with haemorrhage, multiorgan failure, and mortality. The emergence and reemergence of RNA viruses continue to pose a significant public health threat worldwide with particular attention to the increasing incidence of flaviviruses, among others Dengue, West Nile Virus, and Yellow Fever viruses. Development of new and potent antivirals is thus urgently needed. Ivermectin, an already known antihelminthic drug, has shown potent effectsin vitroonFlavivirushelicase, with EC50values in the subnanomolar range for Yellow Fever and submicromolar EC50for Dengue Fever, Japanese encephalitis, and tick-borne encephalitis viruses. However ivermectin is hampered in its application by pharmacokinetic problems (little solubility and high cytotoxicity). To overcome such problems we engineered different compositions of liposomes as ivermectin carriers characterizing and testing them on several cell lines for cytotoxicity. The engineered liposomes were less cytotoxic than ivermectin alone and they showed a significant increase of the antiviral activity in all the Dengue stains tested (1, 2, and S221). In the current study ivermectin is confirmed to be an effective potential antiviral and liposomes, as drug carriers, are shown to modulate the drug activity. All together the results represent a promising starting point for future improvement of ivermectin as antiviral and its delivery.

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Viral strategies of manipulating autophagy to benefit infection

10.20944/preprints201905.0126.v1 ◽

2019 ◽

Author(s):

Ho Him Wong ◽

Sumana Sanyal

Keyword(s):

Rna Virus ◽

Critical Role ◽

Intracellular Pathogens ◽

Virus Infections ◽

Central Process ◽

Conservation Of Energy ◽

Evolutionarily Conserved ◽

Cellular Defence ◽

Host Metabolism ◽

Fine Tune

Autophagy is an evolutionarily conserved central process in host metabolism. Among its major functions are conservation of energy during starvation, recycling organelles, and turnover of long-lived proteins. Besides, autophagy plays a critical role in removing intracellular pathogens and very likely represents a primordial intrinsic cellular defence mechanism. More recent findings indicate that it has not only retained its ability to degrade intracellular pathogens, but also functions to augment and fine tune antiviral immune responses. Interestingly, viruses have also co-evolved strategies to manipulate this pathway and use it to their advantage. Particularly intriguing is infection-dependent activation of autophagy with positive stranded (+)RNA virus infections, which benefit from the pathway without succumbing to lysosomal degradation. In this review we summarise recent data on viral manipulation of autophagy, with a particular emphasis on +RNA viruses and highlight key unanswered questions in the field that we believe merit further attention.

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Analysis of Porcine RIG-I Like Receptors Revealed the Positive Regulation of RIG-I and MDA5 by LGP2

Frontiers in Immunology ◽

10.3389/fimmu.2021.609543 ◽

2021 ◽

Vol 12 ◽

Author(s):

Shuangjie Li ◽

Jie Yang ◽

Yuanyuan Zhu ◽

Hui Wang ◽

Xingyu Ji ◽

...

Keyword(s):

Cell Activation ◽

Viral Infections ◽

Rna Virus ◽

Gene Knockout ◽

Constitutive Activity ◽

Virus Infections ◽

Positive Regulation ◽

Dsrna Binding ◽

Livestock Animal ◽

Signaling Activity

The RLRs play critical roles in sensing and fighting viral infections especially RNA virus infections. Despite the extensive studies on RLRs in humans and mice, there is a lack of systemic investigation of livestock animal RLRs. In this study, we characterized the porcine RLR members RIG-I, MDA5 and LGP2. Compared with their human counterparts, porcine RIG-I and MDA5 exhibited similar signaling activity to distinct dsRNA and viruses, via similar and cooperative recognitions. Porcine LGP2, without signaling activity, was found to positively regulate porcine RIG-I and MDA5 in transfected porcine alveolar macrophages (PAMs), gene knockout PAMs and PK-15 cells. Mechanistically, LGP2 interacts with RIG-I and MDA5 upon cell activation, and promotes the binding of dsRNA ligand by MDA5 as well as RIG-I. Accordingly, porcine LGP2 exerted broad antiviral functions. Intriguingly, we found that porcine LGP2 mutants with defects in ATPase and/or dsRNA binding present constitutive activity which are likely through RIG-I and MDA5. Our work provided significant insights into porcine innate immunity, species specificity and immune biology.

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tRNA 2′-O-methylation by a duo of TRM7/FTSJ1 proteins modulates small RNA silencing in Drosophila

Nucleic Acids Research ◽

10.1093/nar/gkaa002 ◽

2020 ◽

Vol 48 (4) ◽

pp. 2050-2072 ◽

Cited By ~ 4

Author(s):

Margarita T Angelova ◽

Dilyana G Dimitrova ◽

Bruno Da Silva ◽

Virginie Marchand ◽

Caroline Jacquier ◽

...

Keyword(s):

Small Rna ◽

Rna Structure ◽

Rna Silencing ◽

Defense Mechanisms ◽

Rna Virus ◽

Virus Infections ◽

Self Recognition ◽

Silencing Pathways ◽

Rna Pathways ◽

And Function

Abstract 2′-O-Methylation (Nm) represents one of the most common RNA modifications. Nm affects RNA structure and function with crucial roles in various RNA-mediated processes ranging from RNA silencing, translation, self versus non-self recognition to viral defense mechanisms. Here, we identify two Nm methyltransferases (Nm-MTases) in Drosophila melanogaster (CG7009 and CG5220) as functional orthologs of yeast TRM7 and human FTSJ1. Genetic knockout studies together with MALDI-TOF mass spectrometry and RiboMethSeq mapping revealed that CG7009 is responsible for methylating the wobble position in tRNAPhe, tRNATrp and tRNALeu, while CG5220 methylates position C32 in the same tRNAs and also targets additional tRNAs. CG7009 or CG5220 mutant animals were viable and fertile but exhibited various phenotypes such as lifespan reduction, small RNA pathways dysfunction and increased sensitivity to RNA virus infections. Our results provide the first detailed characterization of two TRM7 family members in Drosophila and uncover a molecular link between enzymes catalyzing Nm at specific tRNAs and small RNA-induced gene silencing pathways.

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Alterations in fatty acid metabolism during RNA virus infections

10.5353/th_991044146581503414 ◽

2019 ◽

Author(s):

João Palma Neves Pombo

Keyword(s):

Fatty Acid ◽

Fatty Acid Metabolism ◽

Acid Metabolism ◽

Rna Virus ◽

Virus Infections

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Antiviral activities of ISG20 in positive-strand RNA virus infections

Virology ◽

10.1016/j.virol.2010.10.008 ◽

2011 ◽

Vol 409 (2) ◽

pp. 175-188 ◽

Cited By ~ 54

Author(s):

Zhi Zhou ◽

Nan Wang ◽

Sara E. Woodson ◽

Qingming Dong ◽

Jie Wang ◽

...

Keyword(s):

Rna Virus ◽

Virus Infections ◽

Positive Strand ◽

Antiviral Activities ◽

Positive Strand Rna Virus ◽

Positive Strand Rna

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Reducing false-positive SARS-CoV-2 diagnoses using long-range RT-qPCR

10.1101/2021.11.11.21266219 ◽

2021 ◽

Author(s):

Aartjan J.W. te Velthuis ◽

Dovile Juozapaite ◽

Charlotte Rigby ◽

Ingrida Olendraite ◽

Pankaj Mathur ◽

...

Keyword(s):

Rna Virus ◽

Quantitative Polymerase Chain Reaction ◽

Diagnostic Testing ◽

Genetic Material ◽

Viral Rna ◽

Clinical Samples ◽

Virus Infections ◽

Molecular Method ◽

Polymerase Chain ◽

Positive Results

Quantitative polymerase chain reaction (qPCR) is a sensitive molecular method for the detection of genetic material and regarded as the gold-standard for diagnostic testing. To detect respiratory RNA virus infections, a reverse transcription (RT) step is implemented to create cDNA molecules that can serve as template in the qPCR step. However, positive RT-qPCR results can be found long after patient recovery, in part because the RT-qPCR can detect residual viral RNA genome fragments. To minimize the detection of such fragments, we here modified the RT-qPCR assay by replacing the routinely used random hexamers with an oligonucleotide that binds to the 3' end of the viral genome. We demonstrate that this method allows us to distinguish between infectious and non-infectious samples. Moreover, in clinical samples obtained over 15 days after the onset of symptoms, we observe that the modified RT-qPCR protocol yields significantly fewer positive results compared to a commercial RT-qPCR test. No significantly different results were found compared to the commercial test when SARS-CoV-2 clinical samples were tested within 5 days of the onset of symptoms, suggesting that the modification has a similar sensitivity for detecting infectious viral RNA. Overall, these findings may help differentiate between incorrectly-positive, persistently positive, and reinfection cases in COVID-19 patients.

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Dengue virus: A review

Indian Journal of Pharmacy and Pharmacology ◽

10.18231/j.ijpp.2021.043 ◽

2022 ◽

Vol 8 (4) ◽

pp. 243-247

Author(s):

Narinder Singh ◽

Ajeet Pal Singh ◽

Amar Pal Singh

Keyword(s):

Public Health ◽

Dengue Virus ◽

Dengue Fever ◽

Rna Virus ◽

Hemorrhagic Fever ◽

Health Concern ◽

Virus Infections ◽

Public Health Concern ◽

Viral Illness ◽

Life Threatening

Dengue fever is a mosquito-borne viral illness that is quickly spreading over the globe, with significant death and morbidity rates. Dengue fever is an acute viral infection transmitted by Aedes mosquitos and caused by an RNA virus from the Flaviviridae family. The symptoms might vary from asymptomatic fever to life-threatening complications including hemorrhagic fever and shock. Although dengue virus infections are normally self-limiting, the disease has become a public health concern in tropical and subtropical countries. Dengue fever is a major public health concern owing to its rapid worldwide spread, and its burdens are now unmet due to a lack of accurate therapy and a simple diagnostic approach for the early stages of illness.

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