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Argonaute-CLIP delineates versatile, functional RNAi networks in Aedes aegypti, a major vector of human viruses.

Argonaute (AGO) proteins bind small RNAs to silence complementary RNA transcripts, and they are central to RNA interference (RNAi). RNAi is critical for regulation of gene expression and antiviral defense in Aedes aegypti mosquitoes, which transmit Zika, chikungunya, dengue, and yellow fever viruses. In mosquitoes, AGO1 mediates miRNA interactions, while AGO2 mediates siRNA interactions. We applied AGO-crosslinking immunoprecipitation (AGO-CLIP) for both AGO1 and AGO2, and we developed a universal software package for CLIP analysis (CLIPflexR), identifying 230 small RNAs and 5,447 small RNA ta

Presence of intracellular viruses in human Cryptosporidium isolates.

UNLABELLED: Cryptosporidium is a major cause of diarrheal illness mainly in children and immunocompromised adults. Disease severity ranges from asymptomatic or self-limited gastroenteritis to acute or chronic diarrhoea which may be associated with systemic features. Intracellular viruses that reside in many parasites have been incriminated in pathogenesis of diseases like trichomoniasis, leishmaniasis etc. Thus we attempted to detect and quantitate the intracellular viruses in Cryptosporidium isolates and sought to seek a relationship if any, with clinical features. Cryptosporidia in stool sam

GC content mismatch of transgene destabilizes RNA virus genomes.

GC content-the proportion of guanine and cytosine nucleotides-varies widely among organisms and viruses. Although GC content is recognized to have biological significance, its functional role in viruses remains poorly understood. Here, we examined the impact of GC-content bias using three positive-sense single-stranded RNA viruses with distinct GC profiles: severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), Japanese encephalitis virus (JEV), and hepatitis C virus (HCV). Variants of the NanoLuc (Nluc) reporter gene, engineered with synonymous mutations to alter GC content, were inser…

Discovery of a Novel Human Pegivirus in Blood Associated with Hepatitis C Virus Co-Infection.

Hepatitis C virus (HCV) and human pegivirus (HPgV), formerly GBV-C, are the only known human viruses in the Hepacivirus and Pegivirus genera, respectively, of the family Flaviviridae. We present the discovery of a second pegivirus, provisionally designated human pegivirus 2 (HPgV-2), by next-generation sequencing of plasma from an HCV-infected patient with multiple bloodborne exposures who died from sepsis of unknown etiology. HPgV-2 is highly divergent, situated on a deep phylogenetic branch in a clade that includes rodent and bat pegiviruses, with which it shares <32% amino acid identity. Mo

Discovery and structural characterization of monkeypox virus methyltransferase VP39 inhibitors reveal similarities to SARS-CoV-2 nsp14 methyltransferase.

Monkeypox is a disease with pandemic potential. It is caused by the monkeypox virus (MPXV), a double-stranded DNA virus from the Poxviridae family, that replicates in the cytoplasm and must encode for its own RNA processing machinery including the capping machinery. Here, we present crystal structures of its 2'-O-RNA methyltransferase (MTase) VP39 in complex with the pan-MTase inhibitor sinefungin and a series of inhibitors that were discovered based on it. A comparison of this 2'-O-RNA MTase with enzymes from unrelated single-stranded RNA viruses (SARS-CoV-2 and Zika) reveals a conserved sine…

Ribavirin's antiviral mechanism of action: lethal mutagenesis?

Ribavirin, an antiviral drug discovered in 1972, is interesting and important for three reasons: (a) it exhibits antiviral activity against a broad range of RNA viruses; (b) it is currently used clinically to treat hepatitis C virus infections, respiratory syncytial virus infections, and Lassa fever virus infections; and (c) ribavirin's mechanism of action has remained unclear for many years. Here we recount the history of ribavirin and review recent reports regarding ribavirin's mechanism of action, including our studies demonstrating that ribavirin is an RNA virus mutagen and ribavirin's pri…

[Increase in the antiviral resistance of cells after treating them with messenger RNA for antiviral protein].

The authors studied antiviral resistance of murine cells L-929 following single introduction into them of homologous and heterologous informative RNA preparations for antiviral protein (i-RNA-AVP). As shown, in using homologous i-RVA-AVP preparations suppression of the virus production constituted 90--93%, and was stably traced in cell passage in the course of 1 1/2 months (observation period). Following cell contact with heterologous i-RNA-AVP preparations suppression the first 6 passages of the virus production constituted about 90%, rising by the 16th passage to 99.9%. The data obtained poi

Flavivirus Infection Impairs Peroxisome Biogenesis and Early Antiviral Signaling.

UNLABELLED: Flaviviruses are significant human pathogens that have an enormous impact on the global health burden. Currently, there are very … by which flaviviruses evade the innate immune system during early stages of infection. IMPORTANCE: RNA viruses infect hundreds of millions of people each year, causing significant morbidity and mortality. Chief among these pathogens are the flaviviruses, which include dengue virus and West Nile virus. Despite their medical importance, there are very few prop …

DDX17 and viral infection.

DDX17 (DEAD-box RNA helicase 17) is an essential RNA helicase and regulatory ATPase in host cells, extensively involved in various cellular processes during viral infections, such as RNA splicing, transcriptional regulation, and post-transcriptional modification. DDX17 exhibits dual functionality in viral infections: it enhances the stability, packaging, and replication of viral RNA through interactions with viral ribonucleoprotein complexes, as evidenced in infections caused by influenza viruses and Hantaan virus (HTNV). Conversely, DDX17 can inhibit viral proliferation by disrupting viral RN

IFN alpha inducible protein 27 (IFI27) acts as a positive regulator of PACT-dependent PKR activation after RNA virus infections.

Protein kinase R (PKR) expression is induced by interferons. This protein is activated by double-stranded (ds) RNAs or RNAs containing duplex regions, produced after different stimuli, such as after viral infections, leading to the phosphorylation of the eukaryotic translation initiation factor 2α (eIF2α), and subsequently inhibiting cellular and viral protein translation. This function may lead to different effects such as to impairing the replication of RNA viruses by inhibiting viral protein translation, and to modulating the innate immune responses after viral infections by affecting the t…

RNA structure modulates Cas13 activity and enables mismatch detection.

Cas13 is activated by the hybridization of a CRISPR RNA to a complementary single-stranded RNA protospacer in a target RNA. While Cas13 is not activated by double-stranded RNA in vitro, it robustly targets RNA in cellular environments where RNAs are highly structured. The mechanism by which Cas13 targets structured RNAs remains unknown. Here, we systematically probe the effects of secondary structure on Cas13. We find that secondary structure in the protospacer and 3' to it inhibits Cas13 activity and quantitatively explains the former effect through a strand displacement framework. We then ha

Antiviral Properties of Alginate-Based Biomaterials: Promising Antiviral Agents against SARS-CoV-2.

The COVID-19 pandemic has made it essential to explore alternative antiviral materials. Alginate is a biodegradable, renewable, biocompatibl … cco mosaic virus and the potato virus X. Many of these are enveloped positive-sense single-stranded RNA viruses, like SARS-CoV-2, which render alginate-based materials highly promising in the COVID-19 pandemic.

Молекулярная патогенность энтеровирусов, вызывающих неврологические заболевания.

Enteroviruses - это однострунные вирусы РНК, которые вызывают главным образом желудочно-кишечные или респираторные заболевания. В некоторых случаях эти вирусы могут вторгаться в центральную нервную систему, вызывая опасные для жизни неврологические заболевания, включая энцефалит, менингит и острый легкий паралич (АФП). По мере того как мы приближаемся к глобальному искоренению полиомиелитвируса, который ранее был основной причиной АФП, число случаев заболевания АФП не уменьшается, что подразумевает неполиовирусную этиологию. По мере увеличения числа энтеровирусов, связанных с неврологическими

Совпадение в аннотации оригинала
Enteroviruses are single-stranded positive-sense RNA viruses that primarily cause self-limiting gastrointestinal or respiratory illness. In some cases, these viruses can invade the central nervous system, causing life-threatening neurological diseases including encephalitis, meningitis and acute flaccid paralysis (AFP). As we near the global eradication of p…

Utilisation of ISA Reverse Genetics and Large-Scale Random Codon Re-Encoding to Produce Attenuated Strains of Tick-Borne Encephalitis Virus within Days.

Large-scale codon re-encoding is a new method of attenuating RNA viruses. However, the use of infectious clones to generate attenuated viruses has inherent technical problems. We previously developed a bacterium-free reverse genetics protocol, designated ISA, and now combined it with large-scale random codon-re-encoding method to produce attenuated tick-borne encephalitis virus (TBEV), a pathogenic flavivirus which causes febrile illness and encephalitis in humans. We produced wild-type (WT) and two re-encoded TBEVs, containing 273 or 273+284 synonymous mutations in the NS5 and NS5+NS3 coding …

Domain III peptides from flavivirus envelope protein are useful antigens for serologic diagnosis and targets for immunization.

The Flavivirus genus of the Flaviviridae family includes 70 enveloped single-stranded-RNA positive-sense viruses transmitted by arthropods. Among these viruses, there are a relevant number of human pathogens including the mosquito-borne dengue virus (DENV), yellow fever virus (YFV), Japanese encephalitis virus (JEV) and West Nile virus (WNV), as well as tick-borne viruses such as tick-borne encephalitis virus (TBEV), Langat virus (LGTV) and Omsk hemorrhagic fever (OHFV). The flavivirus envelope (E) protein is a dominant antigen inducing immunologic responses in infected hosts and eliciting vir

Isolation and Molecular Analysis of Negeviruses in Mosquitoes (Diptera: Culicidae) from an Environmental Protection Area in the Brazilian Amazon.

Mosquitoes are recognized as the arthropod group with the greatest vectorial capacity, and the viruses they transmit constitute a significant concern in the context of global One Health. In addition, these insects act as hosts for a wide diversity of insect-specific viruses (ISVs), which exclusively infect arthropods. Expanding knowledge of ISVs is particularly relevant, given their potential influence on arbovirus replication and their role in elucidating the evolutionary processes that shape virus-vector interactions. In this study, we report the isolation and molecular analysis of three neg

Spatiotemporal evolution of the distribution of Chronic bee paralysis virus (CBPV) in honey bee colonies.

Chronic bee paralysis virus (CBPV) is a Apis mellifera viral infectious disease, exhibiting dark and hairless abdomen in workers with tremors and ataxita. Clinical signs are also typically linked to adverse weather conditions and overcrowding in the hive. The disease occurs in spring but recently it has been observed cases increase and seasonality loss of the disease incidence. This study analyses the evolution of CBPV in Italy, through data collected from 2009 to 2023 within three monitoring projects comprising nationwide extended detection networks, aimed to investigate the evolution of the

Common vole (Microtus arvalis) and bank vole (Myodes glareolus) derived permanent cell lines differ in their susceptibility and replication kinetics of animal and zoonotic viruses.

Pathogenesis and reservoir host adaptation of animal and zoonotic viruses are poorly understood due to missing adequate cell culture and animal models. The bank vole (Myodes glareolus) and common vole (Microtus arvalis) serve as hosts for a variety of zoonotic pathogens. For a better understanding of virus association to a putative animal host, we generated two novel cell lines from bank voles of different evolutionary lineages and two common vole cell lines and assayed their susceptibility, replication and cytopathogenic effect (CPE) formation for rodent-borne, suspected to be rodent-associat

Engineering a live-attenuated porcine reproductive and respiratory syndrome virus vaccine to prevent RNA recombination by rewiring transcriptional regulatory sequences.

UNLABELLED: Recombination is a significant factor driving the evolution of RNA viruses. The prevalence and variation of porcine reproductive and respiratory syndrome virus (PRRSV) in China have been increasing in complexity due to extensive interlineage recombination. When this recombination phenomenon occurs in live vaccine strains, it becomes increasingly difficult to prevent and control PRRSV. Reverse genetic manipulation to engineer a different transcriptional regulatory sequence (TRS) circuit introduces genetic traps into the viral genome that are lethal to recombinant RNA progeny viruses…