1,720,965 research outputs found
Role of zinc-finger antiviral protein in restricting RNA viruses
No full textThe zinc finger antiviral protein (ZAP) selectively binds RNAs containing high numbers of CpG dinucleotides and mediates their degradation via its cofactors tripartite motif-containing protein 25 (TRIM25) and KH and NYN domain-containing protein (KHNYN). To evade this restriction, many RNA viruses, including human immunodeficiency virus 1 (HIV-1) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), show a marked suppression of CpG dinucleotides in their genomes, mimicking the dinucleotide composition of their vertebrate hosts. ZAP has been suggested to be one of the driving forces behind CpG suppression in viral genomes. However, it remained unclear whether the CpG suppression of viruses, such as HIV-1 and SARS-CoV-2 is sufficient to completely evade ZAP-mediated restriction. Furthermore, it remained unclear whether ZAP sensitivity of viral pathogens is simply determined by the frequency of CpGs or localization and structural environment also play a role.
To answer these open questions, I analysed the level of restriction exerted by ZAP and the determinants of ZAP sensitivity in HIV-1 and other primate lentiviruses, as well as SARS-CoV-2. In addition, I wanted to obtain new insights into the role of ZAP and CpG suppression in cross-species transmissions and adaptation of these RNA viruses. My findings revealed that ZAP is expressed in primary target cells of HIV and coronaviruses. CpG dinucleotides are generally suppressed in the genomes of lentiviruses as well as coronaviruses albeit to different extents even among closely related strains. For example, CpG frequency is significantly higher in HIV-2 compared to its precursor SIVsmm infecting sooty mangabeys. In comparison, bat coronaviruses exhibit a broad range of CpG suppression, with the closest relatives of SARS-CoV 2 being the most CpG-depleted. Both primate lentiviruses and SARS CoV-2 are inhibited by endogenous ZAP expression, especially in the presence of IFN. Surprisingly, lentiviral susceptibility to ZAP does not correlate with the overall genomic CpG content. Instead, I identified a ~700 nucleotide region in the 5’ end of the env gene (termed ZAPsen) that predicted ZAP sensitivity of HIV-1 strains. Experimental introduction of additional CpGs in this region inhibited infectious virus production in the presence of ZAP.
Altogether, my findings demonstrate that ZAP is a broadly acting component of the cell-intrinsic antiviral immune responses against diverse RNA viruses. It significantly contributes to the antiviral effects of IFNs. Furthermore, ZAP continues to exert evolutionary pressure on viral CpGs and restricts HIV-1 and SARS-CoV-2, despite the fact that these viruses and their animal precursors are adapted to the low CpG environment in humans
Spike residue 403 affects binding of coronavirus spikes to human ACE2
No full textAbstract
The bat sarbecovirus RaTG13 is a close relative of SARS-CoV-2, the cause of the COVID-19 pandemic. However, this bat virus was most likely unable to directly infect humans since its Spike (S) protein does not interact efficiently with the human ACE2 receptor. Here, we show that a single T403R mutation increases binding of RaTG13 S to human ACE2 and allows VSV pseudoparticle infection of human lung cells and intestinal organoids. Conversely, mutation of R403T in the SARS-CoV-2 S reduces pseudoparticle infection and viral replication. The T403R RaTG13 S is neutralized by sera from individuals vaccinated against COVID-19 indicating that vaccination might protect against future zoonoses. Our data suggest that a positively charged amino acid at position 403 in the S protein is critical for efficient utilization of human ACE2 by S proteins of bat coronaviruses. This finding could help to better predict the zoonotic potential of animal coronaviruses.Deutsche Forschungsgemeinschaft https://doi.org/10.13039/501100001659Bundesministerium für Bildung und Forschung https://doi.org/10.13039/50110000234
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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