RESUMO
The internal ribosome entry site (IRES) RNA of bovine viral diarrhoea virus (BVDV), an economically significant Pestivirus, is required for the cap-independent translation of viral genomic RNA. Thus, it is essential for viral replication and pathogenesis. We applied a combination of high-throughput biochemical RNA structure probing (SHAPE-MaP) and in silico modelling approaches to gain insight into the secondary and tertiary structures of BVDV IRES RNA. Our study demonstrated that BVDV IRES RNA in solution forms a modular architecture composed of three distinct structural domains (I-III). Two regions within domain III are represented in tertiary interactions to form an H-type pseudoknot. Computational modelling of the pseudoknot motif provided a fine-grained picture of the tertiary structure and local arrangement of helices in the BVDV IRES. Furthermore, comparative genomics and consensus structure predictions revealed that the pseudoknot is evolutionarily conserved among many Pestivirus species. These studies provide detailed insight into the structural arrangement of BVDV IRES RNA H-type pseudoknot and encompassing motifs that likely contribute to the optimal functionality of viral cap-independent translation element.
Assuntos
Vírus da Diarreia Viral Bovina , Sítios Internos de Entrada Ribossomal , Diarreia , Vírus da Diarreia Viral Bovina/genética , Humanos , Conformação de Ácido Nucleico , RNA Viral/química , RNA Viral/genética , Replicação ViralRESUMO
Coronaviruses are the causative agents of mild to severe respiratory and intestinal infections in humans. They are the largest RNA viruses, which genomes and encoded RNAs are known to fold into the highly-order structures that play essential roles in the viral replication and infectivity cycle. The recent outbreaks of new pathogenic coronaviruses steered researchers' attention into the possibility of targeting their RNAs directly with novel RNA-specific drugs and therapeutic strategies. In this manuscript, we highlight the recent biochemical and biophysical methodological advancements that yielded more in-depth insight into the structural and functional composition of coronaviruses cis-acting RNA motifs. We discuss the complexity of these RNA regulatory elements, their intermolecular interactions, post-transcriptional regulation, and their potential as druggable targets. We also indicate the location and function of unstructured and highly-conserved regions in coronaviruses RNA genomes representing viable aims for antisense oligonucleotide or CRISPR-based antiviral strategies.
Assuntos
Coronavirus , Antivirais , Coronavirus/genética , Humanos , Motivos de Nucleotídeos , RNA Viral/genética , Replicação ViralRESUMO
Authors are often faced with the decision of whether to maximize traditional impact metrics or minimize costs when choosing where to publish the results of their research. Many subscription-based journals now offer the option of paying an article processing charge (APC) to make their work open. Though such "hybrid" journals make research more accessible to readers, their APCs often come with high price tags and can exclude authors who lack the capacity to pay to make their research accessible. Here, we tested if paying to publish open access in a subscription-based journal benefited authors by conferring more citations relative to closed access articles. We identified 146,415 articles published in 152 hybrid journals in the field of biology from 2013-2018 to compare the number of citations between various types of open access and closed access articles. In a simple generalized linear model analysis of our full dataset, we found that publishing open access in hybrid journals that offer the option confers an average citation advantage to authors of 17.8 citations compared to closed access articles in similar journals. After taking into account the number of authors, Journal Citation Reports 2020 Quartile, year of publication, and Web of Science category, we still found that open access generated significantly more citations than closed access (p < 0.0001). However, results were complex, with exact differences in citation rates among access types impacted by these other variables. This citation advantage based on access type was even similar when comparing open and closed access articles published in the same issue of a journal (p < 0.0001). However, by examining articles where the authors paid an article processing charge, we found that cost itself was not predictive of citation rates (p = 0.14). Based on our findings of access type and other model parameters, we suggest that, in the case of the 152 journals we analyzed, paying for open access does confer a citation advantage. For authors with limited budgets, we recommend pursuing open access alternatives that do not require paying a fee as they still yielded more citations than closed access. For authors who are considering where to submit their next article, we offer additional suggestions on how to balance exposure via citations with publishing costs.
Assuntos
Complexos Atriais Prematuros , Publicação de Acesso Aberto , Humanos , Salários e Benefícios , Benchmarking , BiologiaRESUMO
Human coronaviruses (HCoV) are causative agents of mild to severe intestinal and respiratory infections in humans. In the last 15 years, we have witnessed the emergence of three zoonotic, highly pathogenic HCoVs. Thus, early and accurate detection of these viral pathogens is essential for preventing transmission and providing timely treatment and monitoring of drug resistance. Herein, we applied enhanced darkfield hyperspectral microscopy (EDHM), a novel non-invasive, label-free diagnostic tool, to rapidly and accurately identify two strains of HCoVs, i.e., OC43 and 229E. The EDHM technology allows collecting the optical image with spectral and spatial details in a single measurement without direct contact between the specimen and the sensor. Thus, it can directly map spectral signatures specific for a given viral strain in a complex biological milieu. Our study demonstrated distinct spectral patterns for HCoV-OC43 and HCoV-229E virions in the solution, serving as distinguishable parameters for their differentiation. Furthermore, spectral signatures obtained for both HCoV strains in the infected cells displayed a considerable peak wavelength shift compared to the uninfected cell, indicating that the EDHM is applicable to detect HCoV infection in mammalian cells.