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              <name>Title</name>
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                  <text>Coronavirus</text>
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                  <text>Dominio científico: Coronavirus</text>
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                <text>Up-regulation of Mcl-1 and Bak by coronavirus infection of human, avian and animal cells modulates apoptosis and viral replication.</text>
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                <text>Yanxin Zhong, Ying Liao, Shou Guo Fang, James P Tam, Ding Xiang Liu</text>
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                <text>Virus-induced apoptosis and viral mechanisms that regulate this cell death program are key issues in understanding virus-host interactions and viral pathogenesis. Like many other human and animal viruses, coronavirus infection of mammalian cells induces apoptosis. In this study, the global gene expression profiles are first determined in IBV-infected Vero cells at 24 hours post-infection by Affymetrix array, using avian coronavirus infectious bronchitis virus (IBV) as a model system. It reveals an up-regulation at the transcriptional level of both pro-apoptotic Bak and pro-survival myeloid cell leukemia-1 (Mcl-1). These results were further confirmed both in vivo and in vitro, in IBV-infected embryonated chicken eggs, chicken fibroblast cells and mammalian cells at transcriptional and translational levels, respectively. Interestingly, the onset of apoptosis occurred earlier in IBV-infected mammalian cells silenced with short interfering RNA targeting Mcl-1 (siMcl-1), and was delayed in cells silenced with siBak. IBV progeny production and release were increased in infected Mcl-1 knockdown cells compared to similarly infected control cells, while the contrary was observed in infected Bak knockdown cells. Furthermore, IBV infection-induced up-regulation of GADD153 regulated the expression of Mcl-1. Inhibition of the mitogen-activated protein/extracellular signal-regulated kinase (MEK/ERK) and phosphoinositide 3-kinase (PI3K/Akt) signaling pathways by chemical inhibitors and knockdown of GADD153 by siRNA demonstrated the involvement of ER-stress response in regulation of IBV-induced Mcl-1 expression. These results illustrate the sophisticated regulatory strategies evolved by a coronavirus to modulate both virus-induced apoptosis and viral replication during its replication cycle.</text>
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                <text>DOI: 10.1371/journal.pone.0030191</text>
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                <text>PLoS ONE</text>
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              <name>Title</name>
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                  <text>Coronavirus</text>
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                  <text>Dominio científico: Coronavirus</text>
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      <name>Text</name>
      <description>A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.</description>
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        <name>Dublin Core</name>
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                <text>Profiling of substrate specificities of 3C-like proteases from group 1, 2a, 2b, and 3 coronaviruses.</text>
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                <text>Chi-Pang Chuck, Hak-Fun Chow, David Chi-Cheong Wan, Kam-Bo Wong</text>
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                <text>BACKGROUND: Coronaviruses (CoVs) can be classified into alphacoronavirus (group 1), betacoronavirus (group 2), and gammacoronavirus (group 3) based on diversity of the protein sequences. Their 3C-like protease (3CL(pro)), which catalyzes the proteolytic processing of the polyproteins for viral replication, is a potential target for anti-coronaviral infection. METHODOLOGY/PRINCIPAL FINDINGS: Here, we profiled the substrate specificities of 3CL(pro) from human CoV NL63 (group 1), human CoV OC43 (group 2a), severe acute respiratory syndrome coronavirus (SARS-CoV) (group 2b) and infectious bronchitis virus (IBV) (group 3), by measuring their activity against a substrate library of 19 × 8 of variants with single substitutions at P5 to P3' positions. The results were correlated with structural properties like side chain volume, hydrophobicity, and secondary structure propensities of substituting residues. All 3CL(pro) prefer Gln at P1 position, Leu at P2 position, basic residues at P3 position, small hydrophobic residues at P4 position, and small residues at P1' and P2' positions. Despite 3CL(pro) from different groups of CoVs share many similarities in substrate specificities, differences in substrate specificities were observed at P4 positions, with IBV 3CL(pro) prefers P4-Pro and SARS-CoV 3CL(pro) prefers P4-Val. By combining the most favorable residues at P3 to P5 positions, we identified super-active substrate sequences 'VARLQ↓SGF' that can be cleaved efficiently by all 3CL(pro) with relative activity of 1.7 to 3.2, and 'VPRLQ↓SGF' that can be cleaved specifically by IBV 3CL(pro) with relative activity of 4.3. CONCLUSIONS/SIGNIFICANCE: The comprehensive substrate specificities of 3CL(pro) from each of the group 1, 2a, 2b, and 3 CoVs have been profiled in this study, which may provide insights into a rational design of broad-spectrum peptidomimetic inhibitors targeting the proteases.</text>
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                <text>DOI: 10.1371/journal.pone.0027228</text>
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                <text>PLoS ONE</text>
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                <text>Public Library of Science (PLoS)</text>
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              <name>Title</name>
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                  <text>Coronavirus</text>
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                  <text>Dominio científico: Coronavirus</text>
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      <name>Text</name>
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            <name>Title</name>
            <description>A name given to the resource</description>
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              <elementText elementTextId="1678">
                <text>Profiling of substrate specificity of SARS-CoV 3CL.</text>
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          <element elementId="39">
            <name>Creator</name>
            <description>An entity primarily responsible for making the resource</description>
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              <elementText elementTextId="1679">
                <text>Chi-Pang Chuck, Lin-Tat Chong, Chao Chen, Hak-Fun Chow, David Chi-Cheong Wan, Kam-Bo Wong</text>
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            <name>Description</name>
            <description>An account of the resource</description>
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                <text>BACKGROUND: The 3C-like protease (3CL(pro)) of severe acute respiratory syndrome-coronavirus is required for autoprocessing of the polyprotein, and is a potential target for treating coronaviral infection. METHODOLOGY/PRINCIPAL FINDINGS: To obtain a thorough understanding of substrate specificity of the protease, a substrate library of 198 variants was created by performing saturation mutagenesis on the autocleavage sequence at P5 to P3' positions. The substrate sequences were inserted between cyan and yellow fluorescent proteins so that the cleavage rates were monitored by in vitro fluorescence resonance energy transfer. The relative cleavage rate for different substrate sequences was correlated with various structural properties. P5 and P3 positions prefer residues with high β-sheet propensity; P4 prefers small hydrophobic residues; P2 prefers hydrophobic residues without β-branch. Gln is the best residue at P1 position, but observable cleavage can be detected with His and Met substitutions. P1' position prefers small residues, while P2' and P3' positions have no strong preference on residue substitutions. Noteworthy, solvent exposed sites such as P5, P3 and P3' positions favour positively charged residues over negatively charged one, suggesting that electrostatic interactions may play a role in catalysis. A super-active substrate, which combined the preferred residues at P5 to P1 positions, was found to have 2.8 fold higher activity than the wild-type sequence. CONCLUSIONS/SIGNIFICANCE: Our results demonstrated a strong structure-activity relationship between the 3CL(pro) and its substrate. The substrate specificity profiled in this study may provide insights into a rational design of peptidomimetic inhibitors.</text>
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                <text>2010</text>
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                <text>DOI: 10.1371/journal.pone.0013197</text>
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                <text>PLoS ONE</text>
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                <text>Dissecting virus entry: replication-independent analysis of virus binding, internalization, and penetration using minimal complementation of β-galactosidase.</text>
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            <description>An entity primarily responsible for making the resource</description>
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                <text>Christine Burkard, Louis-Marie Bloyet, Oliver Wicht, Frank J van Kuppeveld, Peter J.M. Rottier, Cornelis A.M. De Haan, Berend-Jan Bosch</text>
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                <text>Studies of viral entry into host cells often rely on the detection of post-entry parameters, such as viral replication or the expression of a reporter gene, rather than on measuring entry per se. The lack of assays to easily detect the different steps of entry severely hampers the analysis of this key process in virus infection. Here we describe novel, highly adaptable viral entry assays making use of minimal complementation of the E. coli β-galactosidase in mammalian cells. Enzyme activity is reconstituted when a small intravirion peptide (α-peptide) is complementing the inactive mutant form ΔM15 of β-galactosidase. The method allows to dissect and to independently detect binding, internalization, and fusion of viruses during host cell entry. Here we use it to confirm and extend current knowledge on the entry process of two enveloped viruses: vesicular stomatitis virus (VSV) and murine hepatitis coronavirus (MHV).</text>
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                <text>DOI: 10.1371/journal.pone.0101762</text>
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                <text>PLoS ONE</text>
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                <text>Regulation of programmed ribosomal frameshifting by co-translational refolding RNA hairpins.</text>
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            <description>An entity primarily responsible for making the resource</description>
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                <text>Che-Pei Cho, Szu-Chieh Lin, Ming-Yuan Chou, Hsiu-Ting Hsu, Kung-Yao Chang</text>
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            <description>An account of the resource</description>
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                <text>RNA structures are unwound for decoding. In the process, they can pause the elongating ribosome for regulation. An example is the stimulation of -1 programmed ribosomal frameshifting, leading to 3' direction slippage of the reading-frame during elongation, by specific pseudoknot stimulators downstream of the frameshifting site. By investigating a recently identified regulatory element upstream of the SARS coronavirus (SARS-CoV) -1 frameshifting site, it is shown that a minimal functional element with hairpin forming potential is sufficient to down-regulate-1 frameshifting activity. Mutagenesis to disrupt or restore base pairs in the potential hairpin stem reveals that base-pair formation is required for-1 frameshifting attenuation in vitro and in 293T cells. The attenuation efficiency of a hairpin is determined by its stability and proximity to the frameshifting site; however, it is insensitive to E site sequence variation. Additionally, using a dual luciferase assay, it can be shown that a hairpin stimulated +1 frameshifting when placed upstream of a +1 shifty site in yeast. The investigations indicate that the hairpin is indeed a cis-acting programmed reading-frame switch modulator. This result provides insight into mechanisms governing-1 frameshifting stimulation and attenuation. Since the upstream hairpin is unwound (by a marching ribosome) before the downstream stimulator, this study's findings suggest a new mode of translational regulation that is mediated by the reformed stem of a ribosomal unwound RNA hairpin during elongation.</text>
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                <text>2013</text>
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                <text>DOI: 10.1371/journal.pone.0062283</text>
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            <description>A related resource from which the described resource is derived</description>
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                <text>PLoS ONE</text>
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            <name>Publisher</name>
            <description>An entity responsible for making the resource available</description>
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                <text>Public Library of Science (PLoS)</text>
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                <text>Science, Medicine</text>
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            <description>A language of the resource</description>
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            <element elementId="50">
              <name>Title</name>
              <description>A name given to the resource</description>
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                  <text>Coronavirus</text>
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              <name>Description</name>
              <description>An account of the resource</description>
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                  <text>Dominio científico: Coronavirus</text>
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      <name>Text</name>
      <description>A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.</description>
    </itemType>
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      <elementSet elementSetId="1">
        <name>Dublin Core</name>
        <description>The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.</description>
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          <element elementId="50">
            <name>Title</name>
            <description>A name given to the resource</description>
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              <elementText elementTextId="1651">
                <text>Crystal structure of Middle East respiratory syndrome coronavirus helicase.</text>
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            <name>Creator</name>
            <description>An entity primarily responsible for making the resource</description>
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              <elementText elementTextId="1652">
                <text>Wei Hao, Justyna Aleksandra Wojdyla, Rong Zhao, Ruiyun Han, Rajat Das, Ivan Zlatev, Muthiah Manoharan, Meitian Wang, Sheng Cui</text>
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            <name>Description</name>
            <description>An account of the resource</description>
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              <elementText elementTextId="1653">
                <text>Middle East respiratory syndrome coronavirus (MERS-CoV) remains a threat to public health worldwide; however, effective vaccine or drug against CoVs remains unavailable. CoV helicase is one of the three evolutionary most conserved proteins in nidoviruses, thus making it an important target for drug development. We report here the first structure of full-length coronavirus helicase, MERS-CoV nsp13. MERS-CoV helicase has multiple domains, including an N-terminal Cys/His rich domain (CH) with three zinc atoms, a beta-barrel domain and a C-terminal SF1 helicase core with two RecA-like subdomains. Our structural analyses show that while the domain organization of nsp13 is conserved throughout nidoviruses, the individual domains of nsp13 are closely related to the equivalent eukaryotic domains of Upf1 helicases. The most distinctive feature differentiating CoV helicases from eukaryotic Upf1 helicases is the interaction between CH domain and helicase core.</text>
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            <name>Date</name>
            <description>A point or period of time associated with an event in the lifecycle of the resource</description>
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                <text>2017</text>
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            <name>Identifier</name>
            <description>An unambiguous reference to the resource within a given context</description>
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              <elementText elementTextId="1655">
                <text>DOI: 10.1371/journal.ppat.1006474</text>
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            <name>Source</name>
            <description>A related resource from which the described resource is derived</description>
            <elementTextContainer>
              <elementText elementTextId="1656">
                <text>PLoS Pathogens</text>
              </elementText>
            </elementTextContainer>
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            <name>Publisher</name>
            <description>An entity responsible for making the resource available</description>
            <elementTextContainer>
              <elementText elementTextId="1657">
                <text>Public Library of Science (PLoS)</text>
              </elementText>
            </elementTextContainer>
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            <name>Coverage</name>
            <description>The spatial or temporal topic of the resource, the spatial applicability of the resource, or the jurisdiction under which the resource is relevant</description>
            <elementTextContainer>
              <elementText elementTextId="1658">
                <text>Biology (General), Immunologic diseases. Allergy</text>
              </elementText>
            </elementTextContainer>
          </element>
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            <name>Language</name>
            <description>A language of the resource</description>
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                <text>EN</text>
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  <item itemId="177" public="1" featured="0">
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        <src>http://socictopen.socict.org/files/original/bc85068281d55a2424792f6887096702.pdf</src>
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          <name>Dublin Core</name>
          <description>The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.</description>
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            <element elementId="50">
              <name>Title</name>
              <description>A name given to the resource</description>
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                <elementText elementTextId="1">
                  <text>Coronavirus</text>
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            <element elementId="41">
              <name>Description</name>
              <description>An account of the resource</description>
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                <elementText elementTextId="2">
                  <text>Dominio científico: Coronavirus</text>
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              </elementTextContainer>
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    <itemType itemTypeId="1">
      <name>Text</name>
      <description>A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.</description>
    </itemType>
    <elementSetContainer>
      <elementSet elementSetId="1">
        <name>Dublin Core</name>
        <description>The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.</description>
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          <element elementId="50">
            <name>Title</name>
            <description>A name given to the resource</description>
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                <text>Identification of the Mechanisms Causing Reversion to Virulence in an Attenuated SARS-CoV for the Design of a Genetically Stable Vaccine.</text>
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            <name>Creator</name>
            <description>An entity primarily responsible for making the resource</description>
            <elementTextContainer>
              <elementText elementTextId="1643">
                <text>Jose M. Jimenez-Guardeño, Jose A Regla-Nava, Jose L. Nieto-Torres, Marta L. DeDiego, Carlos Castaño-Rodriguez, Raul Fernandez-Delgado, Stanley Perlman, Luis Enjuanes</text>
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            </elementTextContainer>
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            <name>Description</name>
            <description>An account of the resource</description>
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              <elementText elementTextId="1644">
                <text>A SARS-CoV lacking the full-length E gene (SARS-CoV-∆E) was attenuated and an effective vaccine. Here, we show that this mutant virus regained fitness after serial passages in cell culture or in vivo, resulting in the partial duplication of the membrane gene or in the insertion of a new sequence in gene 8a, respectively. The chimeric proteins generated in cell culture increased virus fitness in vitro but remained attenuated in mice. In contrast, during SARS-CoV-∆E passage in mice, the virus incorporated a mutated variant of 8a protein, resulting in reversion to a virulent phenotype. When the full-length E protein was deleted or its PDZ-binding motif (PBM) was mutated, the revertant viruses either incorporated a novel chimeric protein with a PBM or restored the sequence of the PBM on the E protein, respectively. Similarly, after passage in mice, SARS-CoV-∆E protein 8a mutated, to now encode a PBM, and also regained virulence. These data indicated that the virus requires a PBM on a transmembrane protein to compensate for removal of this motif from the E protein. To increase the genetic stability of the vaccine candidate, we introduced small attenuating deletions in E gene that did not affect the endogenous PBM, preventing the incorporation of novel chimeric proteins in the virus genome. In addition, to increase vaccine biosafety, we introduced additional attenuating mutations into the nsp1 protein. Deletions in the carboxy-terminal region of nsp1 protein led to higher host interferon responses and virus attenuation. Recombinant viruses including attenuating mutations in E and nsp1 genes maintained their attenuation after passage in vitro and in vivo. Further, these viruses fully protected mice against challenge with the lethal parental virus, and are therefore safe and stable vaccine candidates for protection against SARS-CoV.</text>
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            <name>Date</name>
            <description>A point or period of time associated with an event in the lifecycle of the resource</description>
            <elementTextContainer>
              <elementText elementTextId="1645">
                <text>2015</text>
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            <name>Identifier</name>
            <description>An unambiguous reference to the resource within a given context</description>
            <elementTextContainer>
              <elementText elementTextId="1646">
                <text>DOI: 10.1371/journal.ppat.1005215</text>
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            </elementTextContainer>
          </element>
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            <name>Source</name>
            <description>A related resource from which the described resource is derived</description>
            <elementTextContainer>
              <elementText elementTextId="1647">
                <text>PLoS Pathogens</text>
              </elementText>
            </elementTextContainer>
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          <element elementId="45">
            <name>Publisher</name>
            <description>An entity responsible for making the resource available</description>
            <elementTextContainer>
              <elementText elementTextId="1648">
                <text>Public Library of Science (PLoS)</text>
              </elementText>
            </elementTextContainer>
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            <name>Coverage</name>
            <description>The spatial or temporal topic of the resource, the spatial applicability of the resource, or the jurisdiction under which the resource is relevant</description>
            <elementTextContainer>
              <elementText elementTextId="1649">
                <text>Biology (General), Immunologic diseases. Allergy</text>
              </elementText>
            </elementTextContainer>
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            <name>Language</name>
            <description>A language of the resource</description>
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              <elementText elementTextId="1650">
                <text>EN</text>
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        <src>http://socictopen.socict.org/files/original/cff795668701d47689d615fea37bf145.pdf</src>
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            <element elementId="50">
              <name>Title</name>
              <description>A name given to the resource</description>
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                <elementText elementTextId="1">
                  <text>Coronavirus</text>
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            <element elementId="41">
              <name>Description</name>
              <description>An account of the resource</description>
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                <elementText elementTextId="2">
                  <text>Dominio científico: Coronavirus</text>
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    <itemType itemTypeId="1">
      <name>Text</name>
      <description>A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.</description>
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      <elementSet elementSetId="1">
        <name>Dublin Core</name>
        <description>The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.</description>
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          <element elementId="50">
            <name>Title</name>
            <description>A name given to the resource</description>
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                <text>Correction: Reversal of the Progression of Fatal Coronavirus Infection in Cats by a Broad-Spectrum Coronavirus Protease Inhibitor.</text>
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            <name>Creator</name>
            <description>An entity primarily responsible for making the resource</description>
            <elementTextContainer>
              <elementText elementTextId="1634">
                <text>Yunjeong Kim, Hong-wei LIU, Anushka C Galasiti Kankanamalage, Sahani Weerasekara, Duy H Hua, William  C. Groutas, Kyeong-Ok Chang, Niels C. Pedersen</text>
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            <description>An account of the resource</description>
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                <text>[This corrects the article DOI: 10.1371/journal.ppat.1005531.].</text>
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            <name>Date</name>
            <description>A point or period of time associated with an event in the lifecycle of the resource</description>
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              <elementText elementTextId="1636">
                <text>2016</text>
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            <name>Identifier</name>
            <description>An unambiguous reference to the resource within a given context</description>
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              <elementText elementTextId="1637">
                <text>DOI: 10.1371/journal.ppat.1005650</text>
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            <description>A related resource from which the described resource is derived</description>
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              <elementText elementTextId="1638">
                <text>PLoS Pathogens</text>
              </elementText>
            </elementTextContainer>
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            <name>Publisher</name>
            <description>An entity responsible for making the resource available</description>
            <elementTextContainer>
              <elementText elementTextId="1639">
                <text>Public Library of Science (PLoS)</text>
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          </element>
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            <name>Coverage</name>
            <description>The spatial or temporal topic of the resource, the spatial applicability of the resource, or the jurisdiction under which the resource is relevant</description>
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              <elementText elementTextId="1640">
                <text>Biology (General), Immunologic diseases. Allergy</text>
              </elementText>
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            <name>Language</name>
            <description>A language of the resource</description>
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                <text>EN</text>
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  <item itemId="175" public="1" featured="0">
    <fileContainer>
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        <src>http://socictopen.socict.org/files/original/a9d2ffc7c5751d1786036b857522f472.pdf</src>
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          <name>Dublin Core</name>
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            <element elementId="50">
              <name>Title</name>
              <description>A name given to the resource</description>
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                <elementText elementTextId="1">
                  <text>Coronavirus</text>
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            <element elementId="41">
              <name>Description</name>
              <description>An account of the resource</description>
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                <elementText elementTextId="2">
                  <text>Dominio científico: Coronavirus</text>
                </elementText>
              </elementTextContainer>
            </element>
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    </collection>
    <itemType itemTypeId="1">
      <name>Text</name>
      <description>A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.</description>
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    <elementSetContainer>
      <elementSet elementSetId="1">
        <name>Dublin Core</name>
        <description>The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.</description>
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          <element elementId="50">
            <name>Title</name>
            <description>A name given to the resource</description>
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              <elementText elementTextId="1624">
                <text>The role of viral population diversity in adaptation of bovine coronavirus to new host environments.</text>
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            <name>Creator</name>
            <description>An entity primarily responsible for making the resource</description>
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              <elementText elementTextId="1625">
                <text>Monica K. Borucki, Jonathan E Allen, Haiyin Chen-Harris, Adam Zemla, Gilda Vanier, Shalini Mabery, Clinton Torres, Pamela Hullinger, Tom Slezak</text>
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            <name>Description</name>
            <description>An account of the resource</description>
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              <elementText elementTextId="1626">
                <text>The high mutation rate of RNA viruses enables a diverse genetic population of viral genotypes to exist within a single infected host. In-host genetic diversity could better position the virus population to respond and adapt to a diverse array of selective pressures such as host-switching events. Multiple new coronaviruses, including SARS, have been identified in human samples just within the last ten years, demonstrating the potential of coronaviruses as emergent human pathogens. Deep sequencing was used to characterize genomic changes in coronavirus quasispecies during simulated host-switching. Three bovine nasal samples infected with bovine coronavirus were used to infect human and bovine macrophage and lung cell lines. The virus reproduced relatively well in macrophages, but the lung cell lines were not infected efficiently enough to allow passage of non lab-adapted samples. Approximately 12 kb of the genome was amplified before and after passage and sequenced at average coverages of nearly 950×(454 sequencing) and 38,000×(Illumina). The consensus sequence of many of the passaged samples had a 12 nucleotide insert in the consensus sequence of the spike gene, and multiple point mutations were associated with the presence of the insert. Deep sequencing revealed that the insert was present but very rare in the unpassaged samples and could quickly shift to dominate the population when placed in a different environment. The insert coded for three arginine residues, occurred in a region associated with fusion entry into host cells, and may allow infection of new cell types via heparin sulfate binding. Analysis of the deep sequencing data indicated that two distinct genotypes circulated at different frequency levels in each sample, and support the hypothesis that the mutations present in passaged strains were selected" from a pre-existing pool rather than through de novo mutation and subsequent population fixation."</text>
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            <name>Date</name>
            <description>A point or period of time associated with an event in the lifecycle of the resource</description>
            <elementTextContainer>
              <elementText elementTextId="1627">
                <text>2013</text>
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          </element>
          <element elementId="43">
            <name>Identifier</name>
            <description>An unambiguous reference to the resource within a given context</description>
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                <text>CD8(+) T cells provide broad immunity to viruses, because they are able to recognize all types of viral proteins. Therefore, the development of vaccines capable of inducing long-lived memory CD8(+) T cells is desired to prevent diseases, especially those for which no vaccines currently exist. However, in designing CD8(+) T cell vaccines, the role of CD4(+) T cells in the induction and maintenance of memory CD8(+) T cells remains uncertain. In the present study, the necessity or not of CD4(+) T cells in the induction and maintenance of memory CD8(+) T cells was investigated in mice immunized with liposome-coupled CTL epitope peptides. When OVA-derived CTL epitope peptides were chemically coupled to the surfaces of liposomes and inoculated into mice, both primary and secondary CTL responses were successfully induced. The results were further confirmed in CD4(+) T cell-eliminated mice, suggesting that CD4(+) T cells were not required for the generation of memory CD8(+) T cells in the case of immunization with liposome-coupled peptides. Thus, surface-linked liposomal antigens, capable of inducing long-lived memory CD8(+) T cells without the contribution of CD4(+) T cells, might be applicable for the development of vaccines to prevent viral infection, especially for those viruses that evade humoral immunity by varying their surface proteins, such as influenza viruses, HIV, HCV, SARS coronaviruses, and Ebola viruses.</text>
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                <text>DOI: 10.1371/journal.pone.0015091</text>
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