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Intrahost Genetic Diversity of Dengue Virus in Human Hosts and Mosquito Vectors under Natural Conditions Which Impact Replicative Fitness In Vitro

Dengue virus (DENV) is an arbovirus whose transmission cycle involves disparate hosts: humans and mosquitoes. The error-prone nature of viral RNA replication drives the high mutation rates, and the consequently high genetic diversity affects viral fitness over this transmission cycle. A few studies...

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Autores principales: Nonyong, Patcharaporn, Ekalaksananan, Tipaya, Phanthanawiboon, Supranee, Overgaard, Hans J., Alexander, Neal, Thaewnongiew, Kesorn, Sawaswong, Vorthon, Nimsamer, Pattaraporn, Payungporn, Sunchai, Phadungsombat, Juthamas, Nakayama, Emi E., Shioda, Tatsuo, Pientong, Chamsai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10143933/
https://www.ncbi.nlm.nih.gov/pubmed/37112962
http://dx.doi.org/10.3390/v15040982
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author Nonyong, Patcharaporn
Ekalaksananan, Tipaya
Phanthanawiboon, Supranee
Overgaard, Hans J.
Alexander, Neal
Thaewnongiew, Kesorn
Sawaswong, Vorthon
Nimsamer, Pattaraporn
Payungporn, Sunchai
Phadungsombat, Juthamas
Nakayama, Emi E.
Shioda, Tatsuo
Pientong, Chamsai
author_facet Nonyong, Patcharaporn
Ekalaksananan, Tipaya
Phanthanawiboon, Supranee
Overgaard, Hans J.
Alexander, Neal
Thaewnongiew, Kesorn
Sawaswong, Vorthon
Nimsamer, Pattaraporn
Payungporn, Sunchai
Phadungsombat, Juthamas
Nakayama, Emi E.
Shioda, Tatsuo
Pientong, Chamsai
author_sort Nonyong, Patcharaporn
collection PubMed
description Dengue virus (DENV) is an arbovirus whose transmission cycle involves disparate hosts: humans and mosquitoes. The error-prone nature of viral RNA replication drives the high mutation rates, and the consequently high genetic diversity affects viral fitness over this transmission cycle. A few studies have been performed to investigate the intrahost genetic diversity between hosts, although their mosquito infections were performed artificially in the laboratory setting. Here, we performed whole-genome deep sequencing of DENV-1 (n = 11) and DENV-4 (n = 13) derived from clinical samples and field-caught mosquitoes from the houses of naturally infected patients, in order to analyze the intrahost genetic diversity of DENV between host types. Prominent differences in DENV intrahost diversity were observed in the viral population structure between DENV-1 and DENV-4, which appear to be associated with differing selection pressures. Interestingly, three single amino acid substitutions in the NS2A (K81R), NS3 (K107R), and NS5 (I563V) proteins in DENV-4 appear to be specifically acquired during infection in Ae. aegypti mosquitoes. Our in vitro study shows that the NS2A (K81R) mutant replicates similarly to the wild-type infectious clone-derived virus, while the NS3 (K107R), and NS5 (I563V) mutants have prolonged replication kinetics in the early phase in both Vero and C6/36 cells. These findings suggest that DENV is subjected to selection pressure in both mosquito and human hosts. The NS3 and NS5 genes may be specific targets of diversifying selection that play essential roles in early processing, RNA replication, and infectious particle production, and they are potentially adaptive at the population level during host switching.
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spelling pubmed-101439332023-04-29 Intrahost Genetic Diversity of Dengue Virus in Human Hosts and Mosquito Vectors under Natural Conditions Which Impact Replicative Fitness In Vitro Nonyong, Patcharaporn Ekalaksananan, Tipaya Phanthanawiboon, Supranee Overgaard, Hans J. Alexander, Neal Thaewnongiew, Kesorn Sawaswong, Vorthon Nimsamer, Pattaraporn Payungporn, Sunchai Phadungsombat, Juthamas Nakayama, Emi E. Shioda, Tatsuo Pientong, Chamsai Viruses Article Dengue virus (DENV) is an arbovirus whose transmission cycle involves disparate hosts: humans and mosquitoes. The error-prone nature of viral RNA replication drives the high mutation rates, and the consequently high genetic diversity affects viral fitness over this transmission cycle. A few studies have been performed to investigate the intrahost genetic diversity between hosts, although their mosquito infections were performed artificially in the laboratory setting. Here, we performed whole-genome deep sequencing of DENV-1 (n = 11) and DENV-4 (n = 13) derived from clinical samples and field-caught mosquitoes from the houses of naturally infected patients, in order to analyze the intrahost genetic diversity of DENV between host types. Prominent differences in DENV intrahost diversity were observed in the viral population structure between DENV-1 and DENV-4, which appear to be associated with differing selection pressures. Interestingly, three single amino acid substitutions in the NS2A (K81R), NS3 (K107R), and NS5 (I563V) proteins in DENV-4 appear to be specifically acquired during infection in Ae. aegypti mosquitoes. Our in vitro study shows that the NS2A (K81R) mutant replicates similarly to the wild-type infectious clone-derived virus, while the NS3 (K107R), and NS5 (I563V) mutants have prolonged replication kinetics in the early phase in both Vero and C6/36 cells. These findings suggest that DENV is subjected to selection pressure in both mosquito and human hosts. The NS3 and NS5 genes may be specific targets of diversifying selection that play essential roles in early processing, RNA replication, and infectious particle production, and they are potentially adaptive at the population level during host switching. MDPI 2023-04-17 /pmc/articles/PMC10143933/ /pubmed/37112962 http://dx.doi.org/10.3390/v15040982 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nonyong, Patcharaporn
Ekalaksananan, Tipaya
Phanthanawiboon, Supranee
Overgaard, Hans J.
Alexander, Neal
Thaewnongiew, Kesorn
Sawaswong, Vorthon
Nimsamer, Pattaraporn
Payungporn, Sunchai
Phadungsombat, Juthamas
Nakayama, Emi E.
Shioda, Tatsuo
Pientong, Chamsai
Intrahost Genetic Diversity of Dengue Virus in Human Hosts and Mosquito Vectors under Natural Conditions Which Impact Replicative Fitness In Vitro
title Intrahost Genetic Diversity of Dengue Virus in Human Hosts and Mosquito Vectors under Natural Conditions Which Impact Replicative Fitness In Vitro
title_full Intrahost Genetic Diversity of Dengue Virus in Human Hosts and Mosquito Vectors under Natural Conditions Which Impact Replicative Fitness In Vitro
title_fullStr Intrahost Genetic Diversity of Dengue Virus in Human Hosts and Mosquito Vectors under Natural Conditions Which Impact Replicative Fitness In Vitro
title_full_unstemmed Intrahost Genetic Diversity of Dengue Virus in Human Hosts and Mosquito Vectors under Natural Conditions Which Impact Replicative Fitness In Vitro
title_short Intrahost Genetic Diversity of Dengue Virus in Human Hosts and Mosquito Vectors under Natural Conditions Which Impact Replicative Fitness In Vitro
title_sort intrahost genetic diversity of dengue virus in human hosts and mosquito vectors under natural conditions which impact replicative fitness in vitro
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10143933/
https://www.ncbi.nlm.nih.gov/pubmed/37112962
http://dx.doi.org/10.3390/v15040982
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