Genetic regions affecting the replication and pathogenicity of dengue virus type 2
Dengue is a mosquito-borne disease that has spread to over 100 countries. Its symptoms vary from the relatively mild acute febrile illness called dengue fever to the much more severe dengue shock syndrome. Dengue is caused by dengue virus (DENV), which belongs to the Flavivirus genus of the family F...
Gespeichert in:
| Veröffentlicht in: | PLoS neglected tropical diseases 2024-01, Vol.18 (1), p.e0011885-e0011885 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e0011885 |
|---|---|
| container_issue | 1 |
| container_start_page | e0011885 |
| container_title | PLoS neglected tropical diseases |
| container_volume | 18 |
| creator | Samune, Yoshihiro Saito, Akatsuki Sasaki, Tadahiro Koketsu, Ritsuko Srimark, Narinee Phadungsombat, Juthamas Yokoyama, Masaru Kotani, Osamu Sato, Hironori Yamanaka, Atsushi Haga, Saori Okamoto, Toru Kurosu, Takeshi Nakayama, Emi E Shioda, Tatsuo |
| description | Dengue is a mosquito-borne disease that has spread to over 100 countries. Its symptoms vary from the relatively mild acute febrile illness called dengue fever to the much more severe dengue shock syndrome. Dengue is caused by dengue virus (DENV), which belongs to the Flavivirus genus of the family Flaviviridae. There are four serotypes of DENV, i.e., DENV1 to DENV4, and each serotype is divided into distinct genotypes. Thailand is an endemic area where all four serotypes of DENV co-circulate. Genome sequencing of the DENV2 that was isolated in Thailand in 2016 and 2017 revealed the emergence of the Cosmopolitan genotype and its co-circulation with the Asian-I genotype. However, it was unclear whether different genotypes have different levels of viral replication and pathogenicity. Focus-forming assay (FFA) results showed that clinical isolates of these genotypes differed in focus size and proliferative capacity. Using circular polymerase extension reaction, we generated parental and chimeric viruses with swapped genes between these two DENV2 genotypes, and compared their focus sizes and infectivity titers using FFA. The results showed that the focus size was larger when the structural proteins and/or non-structural NS1-NS2B proteins were derived from the Cosmopolitan virus. The infectious titers were consistent with the focus sizes. Single-round infectious particle assay results confirmed that chimeric viruses with Cosmopolitan type structural proteins, particularly prM/E, had significantly increased luciferase activity. Replicon assay results showed that Cosmopolitan NS1-NS2B proteins had increased reporter gene expression levels. Furthermore, in interferon-receptor knock-out mice, viruses with Cosmopolitan structural and NS1-NS2B proteins had higher titers in the blood, and caused critical disease courses. These results suggested that differences in the sequences within the structural and NS1-NS2B proteins may be responsible for the differences in replication, pathogenicity, and infectivity between the Asian-I and Cosmopolitan viruses. |
| doi_str_mv | 10.1371/journal.pntd.0011885 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_3069183494</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A781247344</galeid><doaj_id>oai_doaj_org_article_41fb754db4244c05a9a5a5e6dfd43ecb</doaj_id><sourcerecordid>A781247344</sourcerecordid><originalsourceid>FETCH-LOGICAL-c518t-947793644f313643728822b841ad87d4123655c854a5e1d0db42580a8127175d3</originalsourceid><addsrcrecordid>eNptkt9rFDEQxxdRbK3-B6ILgvhyZ35eso-laC0UBNHnkEsmezn2kjXJCvffm_W2pZWShwmTz8x3ZjJN8xajNaYCf97HKQU9rMdQ7BohjKXkz5pz3FG-IoLy5w_uZ82rnPcI8Y5L_LI5oxJ3iCF23vy4hgDFmzZB72PIrXYOTPGhb8sOqnccvNGlPrU62HbUZRd7CN74cmyjay2EfoL2j09TbstxhJa8bl44PWR4s9iL5tfXLz-vvq1uv1_fXF3ergzHsqw6JkRHN4w5iquhgkhJyFYyrK0UlmFCN5wbyZnmgC2yW0a4RFpiIrDgll407095xyFmtYwjK4o2HZaUdawSNyfCRr1XY_IHnY4qaq_-OWLqlU61-QEUw24rOJtFGDOI607zqruxzjIKZltzfVrUUvw9QS7q4LOBYdAB4pQV6TDhhHWSVPTDf-jTxS1Ur6u-Dy6WpM2cVF2K2iQTlM3U-gmqHgsHb2IA56v_UcDHBwE70EPZ5ThM8xfmxyA7gSbFnBO4-wFhpOYNu6tazRumlg2rYe-W5qbtAex90N1K0b-qLsmG</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3069183494</pqid></control><display><type>article</type><title>Genetic regions affecting the replication and pathogenicity of dengue virus type 2</title><source>EZB Free E-Journals</source><source>Directory of Open Access Journals</source><source>PubMed Central Open Access</source><source>Public Library of Science (PLoS)</source><source>PubMed Central</source><creator>Samune, Yoshihiro ; Saito, Akatsuki ; Sasaki, Tadahiro ; Koketsu, Ritsuko ; Srimark, Narinee ; Phadungsombat, Juthamas ; Yokoyama, Masaru ; Kotani, Osamu ; Sato, Hironori ; Yamanaka, Atsushi ; Haga, Saori ; Okamoto, Toru ; Kurosu, Takeshi ; Nakayama, Emi E ; Shioda, Tatsuo</creator><contributor>Stapleford, Kenneth A.</contributor><creatorcontrib>Samune, Yoshihiro ; Saito, Akatsuki ; Sasaki, Tadahiro ; Koketsu, Ritsuko ; Srimark, Narinee ; Phadungsombat, Juthamas ; Yokoyama, Masaru ; Kotani, Osamu ; Sato, Hironori ; Yamanaka, Atsushi ; Haga, Saori ; Okamoto, Toru ; Kurosu, Takeshi ; Nakayama, Emi E ; Shioda, Tatsuo ; Stapleford, Kenneth A.</creatorcontrib><description>Dengue is a mosquito-borne disease that has spread to over 100 countries. Its symptoms vary from the relatively mild acute febrile illness called dengue fever to the much more severe dengue shock syndrome. Dengue is caused by dengue virus (DENV), which belongs to the Flavivirus genus of the family Flaviviridae. There are four serotypes of DENV, i.e., DENV1 to DENV4, and each serotype is divided into distinct genotypes. Thailand is an endemic area where all four serotypes of DENV co-circulate. Genome sequencing of the DENV2 that was isolated in Thailand in 2016 and 2017 revealed the emergence of the Cosmopolitan genotype and its co-circulation with the Asian-I genotype. However, it was unclear whether different genotypes have different levels of viral replication and pathogenicity. Focus-forming assay (FFA) results showed that clinical isolates of these genotypes differed in focus size and proliferative capacity. Using circular polymerase extension reaction, we generated parental and chimeric viruses with swapped genes between these two DENV2 genotypes, and compared their focus sizes and infectivity titers using FFA. The results showed that the focus size was larger when the structural proteins and/or non-structural NS1-NS2B proteins were derived from the Cosmopolitan virus. The infectious titers were consistent with the focus sizes. Single-round infectious particle assay results confirmed that chimeric viruses with Cosmopolitan type structural proteins, particularly prM/E, had significantly increased luciferase activity. Replicon assay results showed that Cosmopolitan NS1-NS2B proteins had increased reporter gene expression levels. Furthermore, in interferon-receptor knock-out mice, viruses with Cosmopolitan structural and NS1-NS2B proteins had higher titers in the blood, and caused critical disease courses. These results suggested that differences in the sequences within the structural and NS1-NS2B proteins may be responsible for the differences in replication, pathogenicity, and infectivity between the Asian-I and Cosmopolitan viruses.</description><identifier>ISSN: 1935-2735</identifier><identifier>ISSN: 1935-2727</identifier><identifier>EISSN: 1935-2735</identifier><identifier>DOI: 10.1371/journal.pntd.0011885</identifier><identifier>PMID: 38190404</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Aquatic insects ; Assaying ; Clinical isolates ; Cloning ; Cytomegalovirus ; Dengue ; Dengue fever ; Dengue hemorrhagic fever ; Disease transmission ; DNA polymerase ; DNA sequencing ; Epidemics ; Gene expression ; Gene sequencing ; Genomes ; Genotypes ; Human diseases ; Infections ; Infectious diseases ; Infectivity ; Nucleotide sequencing ; Pathogenicity ; Pathogens ; Plasmids ; Prevention ; Proteins ; Replication ; Reporter gene ; Risk factors ; Serotypes ; Signs and symptoms ; Structural proteins ; Vector-borne diseases ; Viral diseases ; Viral replication ; Viruses</subject><ispartof>PLoS neglected tropical diseases, 2024-01, Vol.18 (1), p.e0011885-e0011885</ispartof><rights>Copyright: © 2024 Samune et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</rights><rights>COPYRIGHT 2024 Public Library of Science</rights><rights>2024 Samune et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2024 Samune et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c518t-947793644f313643728822b841ad87d4123655c854a5e1d0db42580a8127175d3</cites><orcidid>0000-0002-3439-8331</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,864,2102,2928,23866,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38190404$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Stapleford, Kenneth A.</contributor><creatorcontrib>Samune, Yoshihiro</creatorcontrib><creatorcontrib>Saito, Akatsuki</creatorcontrib><creatorcontrib>Sasaki, Tadahiro</creatorcontrib><creatorcontrib>Koketsu, Ritsuko</creatorcontrib><creatorcontrib>Srimark, Narinee</creatorcontrib><creatorcontrib>Phadungsombat, Juthamas</creatorcontrib><creatorcontrib>Yokoyama, Masaru</creatorcontrib><creatorcontrib>Kotani, Osamu</creatorcontrib><creatorcontrib>Sato, Hironori</creatorcontrib><creatorcontrib>Yamanaka, Atsushi</creatorcontrib><creatorcontrib>Haga, Saori</creatorcontrib><creatorcontrib>Okamoto, Toru</creatorcontrib><creatorcontrib>Kurosu, Takeshi</creatorcontrib><creatorcontrib>Nakayama, Emi E</creatorcontrib><creatorcontrib>Shioda, Tatsuo</creatorcontrib><title>Genetic regions affecting the replication and pathogenicity of dengue virus type 2</title><title>PLoS neglected tropical diseases</title><addtitle>PLoS Negl Trop Dis</addtitle><description>Dengue is a mosquito-borne disease that has spread to over 100 countries. Its symptoms vary from the relatively mild acute febrile illness called dengue fever to the much more severe dengue shock syndrome. Dengue is caused by dengue virus (DENV), which belongs to the Flavivirus genus of the family Flaviviridae. There are four serotypes of DENV, i.e., DENV1 to DENV4, and each serotype is divided into distinct genotypes. Thailand is an endemic area where all four serotypes of DENV co-circulate. Genome sequencing of the DENV2 that was isolated in Thailand in 2016 and 2017 revealed the emergence of the Cosmopolitan genotype and its co-circulation with the Asian-I genotype. However, it was unclear whether different genotypes have different levels of viral replication and pathogenicity. Focus-forming assay (FFA) results showed that clinical isolates of these genotypes differed in focus size and proliferative capacity. Using circular polymerase extension reaction, we generated parental and chimeric viruses with swapped genes between these two DENV2 genotypes, and compared their focus sizes and infectivity titers using FFA. The results showed that the focus size was larger when the structural proteins and/or non-structural NS1-NS2B proteins were derived from the Cosmopolitan virus. The infectious titers were consistent with the focus sizes. Single-round infectious particle assay results confirmed that chimeric viruses with Cosmopolitan type structural proteins, particularly prM/E, had significantly increased luciferase activity. Replicon assay results showed that Cosmopolitan NS1-NS2B proteins had increased reporter gene expression levels. Furthermore, in interferon-receptor knock-out mice, viruses with Cosmopolitan structural and NS1-NS2B proteins had higher titers in the blood, and caused critical disease courses. These results suggested that differences in the sequences within the structural and NS1-NS2B proteins may be responsible for the differences in replication, pathogenicity, and infectivity between the Asian-I and Cosmopolitan viruses.</description><subject>Analysis</subject><subject>Aquatic insects</subject><subject>Assaying</subject><subject>Clinical isolates</subject><subject>Cloning</subject><subject>Cytomegalovirus</subject><subject>Dengue</subject><subject>Dengue fever</subject><subject>Dengue hemorrhagic fever</subject><subject>Disease transmission</subject><subject>DNA polymerase</subject><subject>DNA sequencing</subject><subject>Epidemics</subject><subject>Gene expression</subject><subject>Gene sequencing</subject><subject>Genomes</subject><subject>Genotypes</subject><subject>Human diseases</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Infectivity</subject><subject>Nucleotide sequencing</subject><subject>Pathogenicity</subject><subject>Pathogens</subject><subject>Plasmids</subject><subject>Prevention</subject><subject>Proteins</subject><subject>Replication</subject><subject>Reporter gene</subject><subject>Risk factors</subject><subject>Serotypes</subject><subject>Signs and symptoms</subject><subject>Structural proteins</subject><subject>Vector-borne diseases</subject><subject>Viral diseases</subject><subject>Viral replication</subject><subject>Viruses</subject><issn>1935-2735</issn><issn>1935-2727</issn><issn>1935-2735</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>DOA</sourceid><recordid>eNptkt9rFDEQxxdRbK3-B6ILgvhyZ35eso-laC0UBNHnkEsmezn2kjXJCvffm_W2pZWShwmTz8x3ZjJN8xajNaYCf97HKQU9rMdQ7BohjKXkz5pz3FG-IoLy5w_uZ82rnPcI8Y5L_LI5oxJ3iCF23vy4hgDFmzZB72PIrXYOTPGhb8sOqnccvNGlPrU62HbUZRd7CN74cmyjay2EfoL2j09TbstxhJa8bl44PWR4s9iL5tfXLz-vvq1uv1_fXF3ergzHsqw6JkRHN4w5iquhgkhJyFYyrK0UlmFCN5wbyZnmgC2yW0a4RFpiIrDgll407095xyFmtYwjK4o2HZaUdawSNyfCRr1XY_IHnY4qaq_-OWLqlU61-QEUw24rOJtFGDOI607zqruxzjIKZltzfVrUUvw9QS7q4LOBYdAB4pQV6TDhhHWSVPTDf-jTxS1Ur6u-Dy6WpM2cVF2K2iQTlM3U-gmqHgsHb2IA56v_UcDHBwE70EPZ5ThM8xfmxyA7gSbFnBO4-wFhpOYNu6tazRumlg2rYe-W5qbtAex90N1K0b-qLsmG</recordid><startdate>20240101</startdate><enddate>20240101</enddate><creator>Samune, Yoshihiro</creator><creator>Saito, Akatsuki</creator><creator>Sasaki, Tadahiro</creator><creator>Koketsu, Ritsuko</creator><creator>Srimark, Narinee</creator><creator>Phadungsombat, Juthamas</creator><creator>Yokoyama, Masaru</creator><creator>Kotani, Osamu</creator><creator>Sato, Hironori</creator><creator>Yamanaka, Atsushi</creator><creator>Haga, Saori</creator><creator>Okamoto, Toru</creator><creator>Kurosu, Takeshi</creator><creator>Nakayama, Emi E</creator><creator>Shioda, Tatsuo</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7SS</scope><scope>7T2</scope><scope>7T7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8C1</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>F1W</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>H95</scope><scope>H97</scope><scope>K9.</scope><scope>L.G</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-3439-8331</orcidid></search><sort><creationdate>20240101</creationdate><title>Genetic regions affecting the replication and pathogenicity of dengue virus type 2</title><author>Samune, Yoshihiro ; Saito, Akatsuki ; Sasaki, Tadahiro ; Koketsu, Ritsuko ; Srimark, Narinee ; Phadungsombat, Juthamas ; Yokoyama, Masaru ; Kotani, Osamu ; Sato, Hironori ; Yamanaka, Atsushi ; Haga, Saori ; Okamoto, Toru ; Kurosu, Takeshi ; Nakayama, Emi E ; Shioda, Tatsuo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c518t-947793644f313643728822b841ad87d4123655c854a5e1d0db42580a8127175d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Analysis</topic><topic>Aquatic insects</topic><topic>Assaying</topic><topic>Clinical isolates</topic><topic>Cloning</topic><topic>Cytomegalovirus</topic><topic>Dengue</topic><topic>Dengue fever</topic><topic>Dengue hemorrhagic fever</topic><topic>Disease transmission</topic><topic>DNA polymerase</topic><topic>DNA sequencing</topic><topic>Epidemics</topic><topic>Gene expression</topic><topic>Gene sequencing</topic><topic>Genomes</topic><topic>Genotypes</topic><topic>Human diseases</topic><topic>Infections</topic><topic>Infectious diseases</topic><topic>Infectivity</topic><topic>Nucleotide sequencing</topic><topic>Pathogenicity</topic><topic>Pathogens</topic><topic>Plasmids</topic><topic>Prevention</topic><topic>Proteins</topic><topic>Replication</topic><topic>Reporter gene</topic><topic>Risk factors</topic><topic>Serotypes</topic><topic>Signs and symptoms</topic><topic>Structural proteins</topic><topic>Vector-borne diseases</topic><topic>Viral diseases</topic><topic>Viral replication</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Samune, Yoshihiro</creatorcontrib><creatorcontrib>Saito, Akatsuki</creatorcontrib><creatorcontrib>Sasaki, Tadahiro</creatorcontrib><creatorcontrib>Koketsu, Ritsuko</creatorcontrib><creatorcontrib>Srimark, Narinee</creatorcontrib><creatorcontrib>Phadungsombat, Juthamas</creatorcontrib><creatorcontrib>Yokoyama, Masaru</creatorcontrib><creatorcontrib>Kotani, Osamu</creatorcontrib><creatorcontrib>Sato, Hironori</creatorcontrib><creatorcontrib>Yamanaka, Atsushi</creatorcontrib><creatorcontrib>Haga, Saori</creatorcontrib><creatorcontrib>Okamoto, Toru</creatorcontrib><creatorcontrib>Kurosu, Takeshi</creatorcontrib><creatorcontrib>Nakayama, Emi E</creatorcontrib><creatorcontrib>Shioda, Tatsuo</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Virology and AIDS Abstracts</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Public Health Database (Proquest)</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 3: Aquatic Pollution & Environmental Quality</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>Directory of Open Access Journals</collection><jtitle>PLoS neglected tropical diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Samune, Yoshihiro</au><au>Saito, Akatsuki</au><au>Sasaki, Tadahiro</au><au>Koketsu, Ritsuko</au><au>Srimark, Narinee</au><au>Phadungsombat, Juthamas</au><au>Yokoyama, Masaru</au><au>Kotani, Osamu</au><au>Sato, Hironori</au><au>Yamanaka, Atsushi</au><au>Haga, Saori</au><au>Okamoto, Toru</au><au>Kurosu, Takeshi</au><au>Nakayama, Emi E</au><au>Shioda, Tatsuo</au><au>Stapleford, Kenneth A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic regions affecting the replication and pathogenicity of dengue virus type 2</atitle><jtitle>PLoS neglected tropical diseases</jtitle><addtitle>PLoS Negl Trop Dis</addtitle><date>2024-01-01</date><risdate>2024</risdate><volume>18</volume><issue>1</issue><spage>e0011885</spage><epage>e0011885</epage><pages>e0011885-e0011885</pages><issn>1935-2735</issn><issn>1935-2727</issn><eissn>1935-2735</eissn><abstract>Dengue is a mosquito-borne disease that has spread to over 100 countries. Its symptoms vary from the relatively mild acute febrile illness called dengue fever to the much more severe dengue shock syndrome. Dengue is caused by dengue virus (DENV), which belongs to the Flavivirus genus of the family Flaviviridae. There are four serotypes of DENV, i.e., DENV1 to DENV4, and each serotype is divided into distinct genotypes. Thailand is an endemic area where all four serotypes of DENV co-circulate. Genome sequencing of the DENV2 that was isolated in Thailand in 2016 and 2017 revealed the emergence of the Cosmopolitan genotype and its co-circulation with the Asian-I genotype. However, it was unclear whether different genotypes have different levels of viral replication and pathogenicity. Focus-forming assay (FFA) results showed that clinical isolates of these genotypes differed in focus size and proliferative capacity. Using circular polymerase extension reaction, we generated parental and chimeric viruses with swapped genes between these two DENV2 genotypes, and compared their focus sizes and infectivity titers using FFA. The results showed that the focus size was larger when the structural proteins and/or non-structural NS1-NS2B proteins were derived from the Cosmopolitan virus. The infectious titers were consistent with the focus sizes. Single-round infectious particle assay results confirmed that chimeric viruses with Cosmopolitan type structural proteins, particularly prM/E, had significantly increased luciferase activity. Replicon assay results showed that Cosmopolitan NS1-NS2B proteins had increased reporter gene expression levels. Furthermore, in interferon-receptor knock-out mice, viruses with Cosmopolitan structural and NS1-NS2B proteins had higher titers in the blood, and caused critical disease courses. These results suggested that differences in the sequences within the structural and NS1-NS2B proteins may be responsible for the differences in replication, pathogenicity, and infectivity between the Asian-I and Cosmopolitan viruses.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>38190404</pmid><doi>10.1371/journal.pntd.0011885</doi><orcidid>https://orcid.org/0000-0002-3439-8331</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1935-2735 |
| ispartof | PLoS neglected tropical diseases, 2024-01, Vol.18 (1), p.e0011885-e0011885 |
| issn | 1935-2735 1935-2727 1935-2735 |
| language | eng |
| recordid | cdi_plos_journals_3069183494 |
| source | EZB Free E-Journals; Directory of Open Access Journals; PubMed Central Open Access; Public Library of Science (PLoS); PubMed Central |
| subjects | Analysis Aquatic insects Assaying Clinical isolates Cloning Cytomegalovirus Dengue Dengue fever Dengue hemorrhagic fever Disease transmission DNA polymerase DNA sequencing Epidemics Gene expression Gene sequencing Genomes Genotypes Human diseases Infections Infectious diseases Infectivity Nucleotide sequencing Pathogenicity Pathogens Plasmids Prevention Proteins Replication Reporter gene Risk factors Serotypes Signs and symptoms Structural proteins Vector-borne diseases Viral diseases Viral replication Viruses |
| title | Genetic regions affecting the replication and pathogenicity of dengue virus type 2 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-21T01%3A05%3A08IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Genetic%20regions%20affecting%20the%20replication%20and%20pathogenicity%20of%20dengue%20virus%20type%202&rft.jtitle=PLoS%20neglected%20tropical%20diseases&rft.au=Samune,%20Yoshihiro&rft.date=2024-01-01&rft.volume=18&rft.issue=1&rft.spage=e0011885&rft.epage=e0011885&rft.pages=e0011885-e0011885&rft.issn=1935-2735&rft.eissn=1935-2735&rft_id=info:doi/10.1371/journal.pntd.0011885&rft_dat=%3Cgale_plos_%3EA781247344%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3069183494&rft_id=info:pmid/38190404&rft_galeid=A781247344&rft_doaj_id=oai_doaj_org_article_41fb754db4244c05a9a5a5e6dfd43ecb&rfr_iscdi=true |