{"id":19897,"date":"2022-10-17T11:35:06","date_gmt":"2022-10-17T03:35:06","guid":{"rendered":"https:\/\/tbenews.com\/tbe\/?p=19897"},"modified":"2022-10-17T11:35:48","modified_gmt":"2022-10-17T03:35:48","slug":"snapshot-week-42-2022-different-virulence-of-tbe-virus-strains-may-be-caused-by-the-non-structural-protein-ns5","status":"publish","type":"post","link":"https:\/\/tbenews.com\/tbe\/snapshot-week-42-2022-different-virulence-of-tbe-virus-strains-may-be-caused-by-the-non-structural-protein-ns5\/","title":{"rendered":"Snapshot week 42\/2022
Different virulence of TBE virus strains may be caused by the non-structural protein NS5"},"content":{"rendered":"\n

Goonawardane et al.
Identification of host factors differentially induced by clinically diverse strains of tick-borne encephalitis virus
J Virol.<\/em> 2022;96(18):e0081822. doi:10.1128\/jvi.00818-22<\/p>\n\n\n\n

The clinical outcome of an infection by TBE virus is variable and is \u2013 beside host factors \u2013 dependent on the viral strain. The basis for this diversity remains unknown.<\/p>\n\n\n\n

The positive-sense RNA of TBE virus comprises of about 11 kb and is translated into a polypeptide precursor that is cleaved by cellular and viral proteases to yield three structural proteins (C, prM, E) and seven non-structural proteins: NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5. The latter protein encodes RNA cap methyltransferase and the viral RNA-dependent RNA-polymerase.<\/p>\n\n\n\n

To identify factors that can contribute to the different pathogenicity of TBE virus strains, two strains of different virulence were compared. Strain Vasilchenco (Vs) has been isolated in Siberia, Russia, in 1969 and infectious clones have been generated. This strain causes subclinical infections and shows only minimal cytopathic effects in cell culture. In contrast, strain Hypr, isolated in 1953 from an infected child in Czechoslovakia, is neuro-invasive in mice and exhibits cytopathic effects in cell culture.<\/p>\n\n\n\n

Vs\/Hypr chimeras have been constructed and a novel series of replicons in which the structural genes were replaced with a cis-acting RNA tag Spinach2 to directly visualize RNA and the kinetics of virus replication, e.g., in chimeras in which the regions coding for NS3 and NS5 were exchanged and characterized in mammalian and invertebrate cell lines, and the induction of early host innate defense proteins were analyzed.<\/p>\n\n\n\n

It could be shown that Hypr replicates to higher levels in mammalian cells than the Vs strain, but not in arthropod cells, and the basis for this difference map in the region of NS5. Hypr was associated with significant activation of the innate immune defense proteins IRF-3, caspase-3 and caspase-8, while Vs activated Akt, affording protection against caspase-mediated apoptosis.<\/p>\n\n\n\n

These findings indicate that host cell responses to TBE virus are driven by NS5, and which are responsible for clinical differences of TBE virus strains.<\/p>\n<\/span>","protected":false},"excerpt":{"rendered":"

Goonawardane et al.Identification of host factors differentially induced by clinically diverse strains of tick-borne encephalitis virusJ Virol. 2022;96(18):e0081822. doi:10.1128\/jvi.00818-22 The clinical outcome of an infection by TBE virus is variable and is \u2013 beside host factors \u2013 dependent on the viral strain. The basis for this diversity remains unknown. The positive-sense RNA of TBE virus comprises of about 11 kb and is translated into a polypeptide precursor that is cleaved by cellular and viral proteases to yield three structural proteins (C, prM, E) and seven non-structural proteins: NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5. The latter protein encodes RNA cap methyltransferase and the viral RNA-dependent RNA-polymerase. To identify factors that can contribute to the different pathogenicity of TBE virus strains, two strains of different virulence were compared. Strain Vasilchenco (Vs) has been isolated in Siberia, Russia, in 1969 and infectious clones have been generated. This strain causes subclinical infections and shows only minimal cytopathic effects in cell culture. In contrast, strain Hypr, isolated in 1953 from an infected child in Czechoslovakia, is neuro-invasive in mice and exhibits cytopathic effects in cell culture. Vs\/Hypr chimeras have been constructed and a novel series of replicons in which the structural genes were replaced with a cis-acting RNA tag Spinach2 to directly visualize RNA and the kinetics of virus replication, e.g., in chimeras in which the regions coding for NS3 and NS5 were exchanged and characterized in mammalian and invertebrate cell lines, and the induction of early host innate defense proteins were analyzed. It could be shown that Hypr replicates to higher levels in mammalian cells than the Vs strain, but not in arthropod cells, and the basis for this difference map in the region of NS5. Hypr was associated with significant activation of the innate immune defense proteins IRF-3, caspase-3 and caspase-8, while Vs activated Akt, affording protection against caspase-mediated apoptosis. These findings indicate that host cell responses to TBE virus are driven by NS5, and which are responsible for clinical differences of TBE virus strains.<\/p>\n","protected":false},"author":1354,"featured_media":12864,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"footnotes":""},"categories":[18],"tags":[793,940,547,941,939,549],"coauthors":[581],"class_list":["post-19897","post","type-post","status-publish","format-standard","has-post-thumbnail","category-snapshot","tag-encephalitis","tag-innate-immunity","tag-non-structural-proteins","tag-replicon","tag-strains","tag-virulence"],"yoast_head":"\nSnapshot week 42\/2022 Different virulence of TBE virus strains may be caused by the non-structural protein NS5 - TBE Book<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/tbenews.com\/tbe\/snapshot-week-42-2022-different-virulence-of-tbe-virus-strains-may-be-caused-by-the-non-structural-protein-ns5\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Snapshot week 42\/2022 Different virulence of TBE virus strains may be caused by the non-structural protein NS5 - TBE Book\" \/>\n<meta property=\"og:description\" content=\"Goonawardane et al.Identification of host factors differentially induced by clinically diverse strains of tick-borne encephalitis virusJ Virol. 2022;96(18):e0081822. doi:10.1128\/jvi.00818-22 The clinical outcome of an infection by TBE virus is variable and is \u2013 beside host factors \u2013 dependent on the viral strain. The basis for this diversity remains unknown. The positive-sense RNA of TBE virus comprises of about 11 kb and is translated into a polypeptide precursor that is cleaved by cellular and viral proteases to yield three structural proteins (C, prM, E) and seven non-structural proteins: NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5. The latter protein encodes RNA cap methyltransferase and the viral RNA-dependent RNA-polymerase. To identify factors that can contribute to the different pathogenicity of TBE virus strains, two strains of different virulence were compared. Strain Vasilchenco (Vs) has been isolated in Siberia, Russia, in 1969 and infectious clones have been generated. This strain causes subclinical infections and shows only minimal cytopathic effects in cell culture. In contrast, strain Hypr, isolated in 1953 from an infected child in Czechoslovakia, is neuro-invasive in mice and exhibits cytopathic effects in cell culture. Vs\/Hypr chimeras have been constructed and a novel series of replicons in which the structural genes were replaced with a cis-acting RNA tag Spinach2 to directly visualize RNA and the kinetics of virus replication, e.g., in chimeras in which the regions coding for NS3 and NS5 were exchanged and characterized in mammalian and invertebrate cell lines, and the induction of early host innate defense proteins were analyzed. It could be shown that Hypr replicates to higher levels in mammalian cells than the Vs strain, but not in arthropod cells, and the basis for this difference map in the region of NS5. Hypr was associated with significant activation of the innate immune defense proteins IRF-3, caspase-3 and caspase-8, while Vs activated Akt, affording protection against caspase-mediated apoptosis. These findings indicate that host cell responses to TBE virus are driven by NS5, and which are responsible for clinical differences of TBE virus strains.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/tbenews.com\/tbe\/snapshot-week-42-2022-different-virulence-of-tbe-virus-strains-may-be-caused-by-the-non-structural-protein-ns5\/\" \/>\n<meta property=\"og:site_name\" content=\"TBE Book\" \/>\n<meta property=\"article:published_time\" content=\"2022-10-17T03:35:06+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2022-10-17T03:35:48+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/tbenews.com\/tbe\/wp-content\/uploads\/2017\/11\/TBE-Snapshots.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"1180\" \/>\n\t<meta property=\"og:image:height\" content=\"250\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"Shaqeez\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Shaqeez\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"2 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\\\/\\\/tbenews.com\\\/tbe\\\/snapshot-week-42-2022-different-virulence-of-tbe-virus-strains-may-be-caused-by-the-non-structural-protein-ns5\\\/#article\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/tbenews.com\\\/tbe\\\/snapshot-week-42-2022-different-virulence-of-tbe-virus-strains-may-be-caused-by-the-non-structural-protein-ns5\\\/\"},\"author\":{\"name\":\"Shaqeez\",\"@id\":\"https:\\\/\\\/tbenews.com\\\/tbe\\\/#\\\/schema\\\/person\\\/2bc2ab1f56f93257537a0ce8de903224\"},\"headline\":\"Snapshot week 42\\\/2022 Different virulence of TBE virus strains may be caused by the non-structural protein NS5\",\"datePublished\":\"2022-10-17T03:35:06+00:00\",\"dateModified\":\"2022-10-17T03:35:48+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\\\/\\\/tbenews.com\\\/tbe\\\/snapshot-week-42-2022-different-virulence-of-tbe-virus-strains-may-be-caused-by-the-non-structural-protein-ns5\\\/\"},\"wordCount\":355,\"publisher\":{\"@id\":\"https:\\\/\\\/tbenews.com\\\/tbe\\\/#organization\"},\"image\":{\"@id\":\"https:\\\/\\\/tbenews.com\\\/tbe\\\/snapshot-week-42-2022-different-virulence-of-tbe-virus-strains-may-be-caused-by-the-non-structural-protein-ns5\\\/#primaryimage\"},\"thumbnailUrl\":\"https:\\\/\\\/tbenews.com\\\/tbe\\\/wp-content\\\/uploads\\\/2017\\\/11\\\/TBE-Snapshots.jpg\",\"keywords\":[\"encephalitis\",\"innate immunity\",\"non-structural proteins\",\"replicon\",\"strains\",\"virulence\"],\"articleSection\":[\"Snapshot\"],\"inLanguage\":\"en-US\"},{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/tbenews.com\\\/tbe\\\/snapshot-week-42-2022-different-virulence-of-tbe-virus-strains-may-be-caused-by-the-non-structural-protein-ns5\\\/\",\"url\":\"https:\\\/\\\/tbenews.com\\\/tbe\\\/snapshot-week-42-2022-different-virulence-of-tbe-virus-strains-may-be-caused-by-the-non-structural-protein-ns5\\\/\",\"name\":\"Snapshot week 42\\\/2022 Different virulence of TBE virus strains may be caused by the non-structural protein NS5 - 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The basis for this diversity remains unknown. The positive-sense RNA of TBE virus comprises of about 11 kb and is translated into a polypeptide precursor that is cleaved by cellular and viral proteases to yield three structural proteins (C, prM, E) and seven non-structural proteins: NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5. The latter protein encodes RNA cap methyltransferase and the viral RNA-dependent RNA-polymerase. To identify factors that can contribute to the different pathogenicity of TBE virus strains, two strains of different virulence were compared. Strain Vasilchenco (Vs) has been isolated in Siberia, Russia, in 1969 and infectious clones have been generated. This strain causes subclinical infections and shows only minimal cytopathic effects in cell culture. In contrast, strain Hypr, isolated in 1953 from an infected child in Czechoslovakia, is neuro-invasive in mice and exhibits cytopathic effects in cell culture. Vs\/Hypr chimeras have been constructed and a novel series of replicons in which the structural genes were replaced with a cis-acting RNA tag Spinach2 to directly visualize RNA and the kinetics of virus replication, e.g., in chimeras in which the regions coding for NS3 and NS5 were exchanged and characterized in mammalian and invertebrate cell lines, and the induction of early host innate defense proteins were analyzed. It could be shown that Hypr replicates to higher levels in mammalian cells than the Vs strain, but not in arthropod cells, and the basis for this difference map in the region of NS5. Hypr was associated with significant activation of the innate immune defense proteins IRF-3, caspase-3 and caspase-8, while Vs activated Akt, affording protection against caspase-mediated apoptosis. 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