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Structural mutants of dengue virus 2 transmembrane domains exhibit host-range phenotype

BACKGROUND: There are over 700 known arboviruses and at least 80 immunologically distinct types that cause disease in humans. Arboviruses are transmitted among vertebrates by biting insects, chiefly mosquitoes and ticks. These viruses are widely distributed throughout the world, depending on the pre...

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Autores principales: Smith, Katherine M, Nanda, Kavita, Spears, Carla J, Ribeiro, Mariana, Vancini, Ricardo, Piper, Amanda, Thomas, Gwynneth S, Thomas, Malcolm E, Brown, Dennis T, Hernandez, Raquel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3128863/
https://www.ncbi.nlm.nih.gov/pubmed/21658241
http://dx.doi.org/10.1186/1743-422X-8-289
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author Smith, Katherine M
Nanda, Kavita
Spears, Carla J
Ribeiro, Mariana
Vancini, Ricardo
Piper, Amanda
Thomas, Gwynneth S
Thomas, Malcolm E
Brown, Dennis T
Hernandez, Raquel
author_facet Smith, Katherine M
Nanda, Kavita
Spears, Carla J
Ribeiro, Mariana
Vancini, Ricardo
Piper, Amanda
Thomas, Gwynneth S
Thomas, Malcolm E
Brown, Dennis T
Hernandez, Raquel
author_sort Smith, Katherine M
collection PubMed
description BACKGROUND: There are over 700 known arboviruses and at least 80 immunologically distinct types that cause disease in humans. Arboviruses are transmitted among vertebrates by biting insects, chiefly mosquitoes and ticks. These viruses are widely distributed throughout the world, depending on the presence of appropriate hosts (birds, horses, domestic animals, humans) and vectors. Mosquito-borne arboviruses present some of the most important examples of emerging and resurgent diseases of global significance. METHODS: A strategy has been developed by which host-range mutants of Dengue virus can be constructed by generating deletions in the transmembrane domain (TMD) of the E glycoprotein. The host-range mutants produced and selected favored growth in the insect hosts. Mouse trials were conducted to determine if these mutants could initiate an immune response in an in vivo system. RESULTS: The DV2 E protein TMD defined as amino acids 452SWTMKILIGVIITWIG467 was found to contain specific residues which were required for the production of this host-range phenotype. Deletion mutants were found to be stable in vitro for 4 sequential passages in both host cell lines. The host-range mutants elicited neutralizing antibody above that seen for wild-type virus in mice and warrant further testing in primates as potential vaccine candidates. CONCLUSIONS: Novel host-range mutants of DV2 were created that have preferential growth in insect cells and impaired infectivity in mammalian cells. This method for creating live, attenuated viral mutants that generate safe and effective immunity may be applied to many other insect-borne viral diseases for which no current effective therapies exist.
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spelling pubmed-31288632011-07-04 Structural mutants of dengue virus 2 transmembrane domains exhibit host-range phenotype Smith, Katherine M Nanda, Kavita Spears, Carla J Ribeiro, Mariana Vancini, Ricardo Piper, Amanda Thomas, Gwynneth S Thomas, Malcolm E Brown, Dennis T Hernandez, Raquel Virol J Research BACKGROUND: There are over 700 known arboviruses and at least 80 immunologically distinct types that cause disease in humans. Arboviruses are transmitted among vertebrates by biting insects, chiefly mosquitoes and ticks. These viruses are widely distributed throughout the world, depending on the presence of appropriate hosts (birds, horses, domestic animals, humans) and vectors. Mosquito-borne arboviruses present some of the most important examples of emerging and resurgent diseases of global significance. METHODS: A strategy has been developed by which host-range mutants of Dengue virus can be constructed by generating deletions in the transmembrane domain (TMD) of the E glycoprotein. The host-range mutants produced and selected favored growth in the insect hosts. Mouse trials were conducted to determine if these mutants could initiate an immune response in an in vivo system. RESULTS: The DV2 E protein TMD defined as amino acids 452SWTMKILIGVIITWIG467 was found to contain specific residues which were required for the production of this host-range phenotype. Deletion mutants were found to be stable in vitro for 4 sequential passages in both host cell lines. The host-range mutants elicited neutralizing antibody above that seen for wild-type virus in mice and warrant further testing in primates as potential vaccine candidates. CONCLUSIONS: Novel host-range mutants of DV2 were created that have preferential growth in insect cells and impaired infectivity in mammalian cells. This method for creating live, attenuated viral mutants that generate safe and effective immunity may be applied to many other insect-borne viral diseases for which no current effective therapies exist. BioMed Central 2011-06-09 /pmc/articles/PMC3128863/ /pubmed/21658241 http://dx.doi.org/10.1186/1743-422X-8-289 Text en Copyright ©2011 Smith et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Smith, Katherine M
Nanda, Kavita
Spears, Carla J
Ribeiro, Mariana
Vancini, Ricardo
Piper, Amanda
Thomas, Gwynneth S
Thomas, Malcolm E
Brown, Dennis T
Hernandez, Raquel
Structural mutants of dengue virus 2 transmembrane domains exhibit host-range phenotype
title Structural mutants of dengue virus 2 transmembrane domains exhibit host-range phenotype
title_full Structural mutants of dengue virus 2 transmembrane domains exhibit host-range phenotype
title_fullStr Structural mutants of dengue virus 2 transmembrane domains exhibit host-range phenotype
title_full_unstemmed Structural mutants of dengue virus 2 transmembrane domains exhibit host-range phenotype
title_short Structural mutants of dengue virus 2 transmembrane domains exhibit host-range phenotype
title_sort structural mutants of dengue virus 2 transmembrane domains exhibit host-range phenotype
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3128863/
https://www.ncbi.nlm.nih.gov/pubmed/21658241
http://dx.doi.org/10.1186/1743-422X-8-289
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