Stability of yellow fever virus under recombinatory pressure as compared with chikungunya virus
Recombination is a mechanism whereby positive sense single stranded RNA viruses exchange segments of genetic information. Recent phylogenetic analyses of naturally occurring recombinant flaviviruses have raised concerns regarding the potential for the emergence of virulent recombinants either post-v...
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| creator | McGee, Charles E Tsetsarkin, Konstantin A Guy, Bruno Lang, Jean Plante, Kenneth Vanlandingham, Dana L Higgs, Stephen |
| description | Recombination is a mechanism whereby positive sense single stranded RNA viruses exchange segments of genetic information. Recent phylogenetic analyses of naturally occurring recombinant flaviviruses have raised concerns regarding the potential for the emergence of virulent recombinants either post-vaccination or following co-infection with two distinct wild-type viruses. To characterize the conditions and sequences that favor RNA arthropod-borne virus recombination we constructed yellow fever virus (YFV) 17D recombinant crosses containing complementary deletions in the envelope protein coding sequence. These constructs were designed to strongly favor recombination, and the detection conditions were optimized to achieve high sensitivity recovery of putative recombinants. Full length recombinant YFV 17D virus was never detected under any of the experimental conditions examined, despite achieving estimated YFV replicon co-infection levels of ∼2.4 x 10⁶ in BHK-21 (vertebrate) cells and ∼1.05 x 10⁵ in C₇10 (arthropod) cells. Additionally YFV 17D superinfection resistance was observed in vertebrate and arthropod cells harboring a primary infection with wild-type YFV Asibi strain. Furthermore recombination potential was also evaluated using similarly designed chikungunya virus (CHIKV) replicons towards validation of this strategy for recombination detection. Non-homologus recombination was observed for CHIKV within the structural gene coding sequence resulting in an in-frame duplication of capsid and E3 gene. Based on these data, it is concluded that even in the unlikely event of a high level acute co-infection of two distinct YFV genomes in an arthropod or vertebrate host, the generation of viable flavivirus recombinants is extremely unlikely. |
| doi_str_mv | 10.1371/journal.pone.0023247 |
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Recent phylogenetic analyses of naturally occurring recombinant flaviviruses have raised concerns regarding the potential for the emergence of virulent recombinants either post-vaccination or following co-infection with two distinct wild-type viruses. To characterize the conditions and sequences that favor RNA arthropod-borne virus recombination we constructed yellow fever virus (YFV) 17D recombinant crosses containing complementary deletions in the envelope protein coding sequence. These constructs were designed to strongly favor recombination, and the detection conditions were optimized to achieve high sensitivity recovery of putative recombinants. Full length recombinant YFV 17D virus was never detected under any of the experimental conditions examined, despite achieving estimated YFV replicon co-infection levels of ∼2.4 x 10⁶ in BHK-21 (vertebrate) cells and ∼1.05 x 10⁵ in C₇10 (arthropod) cells. Additionally YFV 17D superinfection resistance was observed in vertebrate and arthropod cells harboring a primary infection with wild-type YFV Asibi strain. Furthermore recombination potential was also evaluated using similarly designed chikungunya virus (CHIKV) replicons towards validation of this strategy for recombination detection. Non-homologus recombination was observed for CHIKV within the structural gene coding sequence resulting in an in-frame duplication of capsid and E3 gene. Based on these data, it is concluded that even in the unlikely event of a high level acute co-infection of two distinct YFV genomes in an arthropod or vertebrate host, the generation of viable flavivirus recombinants is extremely unlikely.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0023247</identifier><identifier>PMID: 21826243</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aedes albopictus ; Amino acid sequence ; Analysis ; Arachnids ; Biology ; Blotting, Northern ; Chikungunya virus ; Chikungunya virus - genetics ; Culicidae ; Dengue fever ; E3 gene ; Encephalitis ; Envelope protein ; Fever ; Flavivirus ; Gene sequencing ; Genetic analysis ; Genome, Viral - genetics ; Genomes ; Genomics ; Hepatitis ; Homology ; Infection ; Infections ; Lipids ; Medicine ; Mosquitoes ; Pathology ; Phylogeny ; Proteins ; Recombinants ; Recombination ; Recombination, Genetic - genetics ; Ribonucleic acid ; RNA ; RNA viruses ; Superinfection ; Vaccination ; Vaccines ; Vector-borne diseases ; Viral envelope proteins ; Virology ; Viruses ; West Nile virus ; World War II ; Yellow fever ; Yellow fever virus - genetics</subject><ispartof>PloS one, 2011-08, Vol.6 (8), p.e23247-e23247</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 McGee et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://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. 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Recent phylogenetic analyses of naturally occurring recombinant flaviviruses have raised concerns regarding the potential for the emergence of virulent recombinants either post-vaccination or following co-infection with two distinct wild-type viruses. To characterize the conditions and sequences that favor RNA arthropod-borne virus recombination we constructed yellow fever virus (YFV) 17D recombinant crosses containing complementary deletions in the envelope protein coding sequence. These constructs were designed to strongly favor recombination, and the detection conditions were optimized to achieve high sensitivity recovery of putative recombinants. Full length recombinant YFV 17D virus was never detected under any of the experimental conditions examined, despite achieving estimated YFV replicon co-infection levels of ∼2.4 x 10⁶ in BHK-21 (vertebrate) cells and ∼1.05 x 10⁵ in C₇10 (arthropod) cells. Additionally YFV 17D superinfection resistance was observed in vertebrate and arthropod cells harboring a primary infection with wild-type YFV Asibi strain. Furthermore recombination potential was also evaluated using similarly designed chikungunya virus (CHIKV) replicons towards validation of this strategy for recombination detection. Non-homologus recombination was observed for CHIKV within the structural gene coding sequence resulting in an in-frame duplication of capsid and E3 gene. Based on these data, it is concluded that even in the unlikely event of a high level acute co-infection of two distinct YFV genomes in an arthropod or vertebrate host, the generation of viable flavivirus recombinants is extremely unlikely.</description><subject>Aedes albopictus</subject><subject>Amino acid sequence</subject><subject>Analysis</subject><subject>Arachnids</subject><subject>Biology</subject><subject>Blotting, Northern</subject><subject>Chikungunya virus</subject><subject>Chikungunya virus - genetics</subject><subject>Culicidae</subject><subject>Dengue fever</subject><subject>E3 gene</subject><subject>Encephalitis</subject><subject>Envelope protein</subject><subject>Fever</subject><subject>Flavivirus</subject><subject>Gene sequencing</subject><subject>Genetic analysis</subject><subject>Genome, Viral - genetics</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Hepatitis</subject><subject>Homology</subject><subject>Infection</subject><subject>Infections</subject><subject>Lipids</subject><subject>Medicine</subject><subject>Mosquitoes</subject><subject>Pathology</subject><subject>Phylogeny</subject><subject>Proteins</subject><subject>Recombinants</subject><subject>Recombination</subject><subject>Recombination, Genetic - 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Recent phylogenetic analyses of naturally occurring recombinant flaviviruses have raised concerns regarding the potential for the emergence of virulent recombinants either post-vaccination or following co-infection with two distinct wild-type viruses. To characterize the conditions and sequences that favor RNA arthropod-borne virus recombination we constructed yellow fever virus (YFV) 17D recombinant crosses containing complementary deletions in the envelope protein coding sequence. These constructs were designed to strongly favor recombination, and the detection conditions were optimized to achieve high sensitivity recovery of putative recombinants. Full length recombinant YFV 17D virus was never detected under any of the experimental conditions examined, despite achieving estimated YFV replicon co-infection levels of ∼2.4 x 10⁶ in BHK-21 (vertebrate) cells and ∼1.05 x 10⁵ in C₇10 (arthropod) cells. Additionally YFV 17D superinfection resistance was observed in vertebrate and arthropod cells harboring a primary infection with wild-type YFV Asibi strain. Furthermore recombination potential was also evaluated using similarly designed chikungunya virus (CHIKV) replicons towards validation of this strategy for recombination detection. Non-homologus recombination was observed for CHIKV within the structural gene coding sequence resulting in an in-frame duplication of capsid and E3 gene. Based on these data, it is concluded that even in the unlikely event of a high level acute co-infection of two distinct YFV genomes in an arthropod or vertebrate host, the generation of viable flavivirus recombinants is extremely unlikely.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21826243</pmid><doi>10.1371/journal.pone.0023247</doi><tpages>e23247</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aedes albopictus Amino acid sequence Analysis Arachnids Biology Blotting, Northern Chikungunya virus Chikungunya virus - genetics Culicidae Dengue fever E3 gene Encephalitis Envelope protein Fever Flavivirus Gene sequencing Genetic analysis Genome, Viral - genetics Genomes Genomics Hepatitis Homology Infection Infections Lipids Medicine Mosquitoes Pathology Phylogeny Proteins Recombinants Recombination Recombination, Genetic - genetics Ribonucleic acid RNA RNA viruses Superinfection Vaccination Vaccines Vector-borne diseases Viral envelope proteins Virology Viruses West Nile virus World War II Yellow fever Yellow fever virus - genetics |
| title | Stability of yellow fever virus under recombinatory pressure as compared with chikungunya virus |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-14T21%3A56%3A42IST&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=Stability%20of%20yellow%20fever%20virus%20under%20recombinatory%20pressure%20as%20compared%20with%20chikungunya%20virus&rft.jtitle=PloS%20one&rft.au=McGee,%20Charles%20E&rft.date=2011-08-03&rft.volume=6&rft.issue=8&rft.spage=e23247&rft.epage=e23247&rft.pages=e23247-e23247&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0023247&rft_dat=%3Cgale_plos_%3EA476883319%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=1307257913&rft_id=info:pmid/21826243&rft_galeid=A476883319&rft_doaj_id=oai_doaj_org_article_d64a6bd125754dbfb3f0dd792ed423e1&rfr_iscdi=true |