author_facet Thai, Khoa T. D.
Henn, Matthew R.
Zody, Michael C.
Tricou, Vianney
Nguyet, Nguyen Minh
Charlebois, Patrick
Lennon, Niall J.
Green, Lisa
de Vries, Peter J.
Hien, Tran Tinh
Farrar, Jeremy
van Doorn, H. Rogier
de Jong, Menno D.
Birren, Bruce W.
Holmes, Edward C.
Simmons, Cameron P.
Thai, Khoa T. D.
Henn, Matthew R.
Zody, Michael C.
Tricou, Vianney
Nguyet, Nguyen Minh
Charlebois, Patrick
Lennon, Niall J.
Green, Lisa
de Vries, Peter J.
Hien, Tran Tinh
Farrar, Jeremy
van Doorn, H. Rogier
de Jong, Menno D.
Birren, Bruce W.
Holmes, Edward C.
Simmons, Cameron P.
author Thai, Khoa T. D.
Henn, Matthew R.
Zody, Michael C.
Tricou, Vianney
Nguyet, Nguyen Minh
Charlebois, Patrick
Lennon, Niall J.
Green, Lisa
de Vries, Peter J.
Hien, Tran Tinh
Farrar, Jeremy
van Doorn, H. Rogier
de Jong, Menno D.
Birren, Bruce W.
Holmes, Edward C.
Simmons, Cameron P.
spellingShingle Thai, Khoa T. D.
Henn, Matthew R.
Zody, Michael C.
Tricou, Vianney
Nguyet, Nguyen Minh
Charlebois, Patrick
Lennon, Niall J.
Green, Lisa
de Vries, Peter J.
Hien, Tran Tinh
Farrar, Jeremy
van Doorn, H. Rogier
de Jong, Menno D.
Birren, Bruce W.
Holmes, Edward C.
Simmons, Cameron P.
Journal of Virology
High-Resolution Analysis of Intrahost Genetic Diversity in Dengue Virus Serotype 1 Infection Identifies Mixed Infections
Virology
Insect Science
Immunology
Microbiology
author_sort thai, khoa t. d.
spelling Thai, Khoa T. D. Henn, Matthew R. Zody, Michael C. Tricou, Vianney Nguyet, Nguyen Minh Charlebois, Patrick Lennon, Niall J. Green, Lisa de Vries, Peter J. Hien, Tran Tinh Farrar, Jeremy van Doorn, H. Rogier de Jong, Menno D. Birren, Bruce W. Holmes, Edward C. Simmons, Cameron P. 0022-538X 1098-5514 American Society for Microbiology Virology Insect Science Immunology Microbiology http://dx.doi.org/10.1128/jvi.05985-11 <jats:title>ABSTRACT</jats:title> <jats:p> Little is known about the rate at which genetic variation is generated within intrahost populations of dengue virus (DENV) and what implications this diversity has for dengue pathogenesis, disease severity, and host immunity. Previous studies of intrahost DENV variation have used a low frequency of sampling and/or experimental methods that do not fully account for errors generated through amplification and sequencing of viral RNAs. We investigated the extent and pattern of genetic diversity in sequence data in domain III (DIII) of the envelope (E) gene in serial plasma samples ( <jats:italic>n</jats:italic> = 49) taken from 17 patients infected with DENV type 1 (DENV-1), totaling some 8,458 clones. Statistically rigorous approaches were employed to account for artifactual variants resulting from amplification and sequencing, which we suggest have played a major role in previous studies of intrahost genetic variation. Accordingly, nucleotide sequence diversities of viral populations were very low, with conservative estimates of the average levels of genetic diversity ranging from 0 to 0.0013. Despite such sequence conservation, we observed clear evidence for mixed infection, with the presence of multiple phylogenetically distinct lineages present within the same host, while the presence of stop codon mutations in some samples suggests the action of complementation. In contrast to some previous studies we observed no relationship between the extent and pattern of DENV-1 genetic diversity and disease severity, immune status, or level of viremia. </jats:p> High-Resolution Analysis of Intrahost Genetic Diversity in Dengue Virus Serotype 1 Infection Identifies Mixed Infections Journal of Virology
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title High-Resolution Analysis of Intrahost Genetic Diversity in Dengue Virus Serotype 1 Infection Identifies Mixed Infections
title_unstemmed High-Resolution Analysis of Intrahost Genetic Diversity in Dengue Virus Serotype 1 Infection Identifies Mixed Infections
title_full High-Resolution Analysis of Intrahost Genetic Diversity in Dengue Virus Serotype 1 Infection Identifies Mixed Infections
title_fullStr High-Resolution Analysis of Intrahost Genetic Diversity in Dengue Virus Serotype 1 Infection Identifies Mixed Infections
title_full_unstemmed High-Resolution Analysis of Intrahost Genetic Diversity in Dengue Virus Serotype 1 Infection Identifies Mixed Infections
title_short High-Resolution Analysis of Intrahost Genetic Diversity in Dengue Virus Serotype 1 Infection Identifies Mixed Infections
title_sort high-resolution analysis of intrahost genetic diversity in dengue virus serotype 1 infection identifies mixed infections
topic Virology
Insect Science
Immunology
Microbiology
url http://dx.doi.org/10.1128/jvi.05985-11
publishDate 2012
physical 835-843
description <jats:title>ABSTRACT</jats:title> <jats:p> Little is known about the rate at which genetic variation is generated within intrahost populations of dengue virus (DENV) and what implications this diversity has for dengue pathogenesis, disease severity, and host immunity. Previous studies of intrahost DENV variation have used a low frequency of sampling and/or experimental methods that do not fully account for errors generated through amplification and sequencing of viral RNAs. We investigated the extent and pattern of genetic diversity in sequence data in domain III (DIII) of the envelope (E) gene in serial plasma samples ( <jats:italic>n</jats:italic> = 49) taken from 17 patients infected with DENV type 1 (DENV-1), totaling some 8,458 clones. Statistically rigorous approaches were employed to account for artifactual variants resulting from amplification and sequencing, which we suggest have played a major role in previous studies of intrahost genetic variation. Accordingly, nucleotide sequence diversities of viral populations were very low, with conservative estimates of the average levels of genetic diversity ranging from 0 to 0.0013. Despite such sequence conservation, we observed clear evidence for mixed infection, with the presence of multiple phylogenetically distinct lineages present within the same host, while the presence of stop codon mutations in some samples suggests the action of complementation. In contrast to some previous studies we observed no relationship between the extent and pattern of DENV-1 genetic diversity and disease severity, immune status, or level of viremia. </jats:p>
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author Thai, Khoa T. D., Henn, Matthew R., Zody, Michael C., Tricou, Vianney, Nguyet, Nguyen Minh, Charlebois, Patrick, Lennon, Niall J., Green, Lisa, de Vries, Peter J., Hien, Tran Tinh, Farrar, Jeremy, van Doorn, H. Rogier, de Jong, Menno D., Birren, Bruce W., Holmes, Edward C., Simmons, Cameron P.
author_facet Thai, Khoa T. D., Henn, Matthew R., Zody, Michael C., Tricou, Vianney, Nguyet, Nguyen Minh, Charlebois, Patrick, Lennon, Niall J., Green, Lisa, de Vries, Peter J., Hien, Tran Tinh, Farrar, Jeremy, van Doorn, H. Rogier, de Jong, Menno D., Birren, Bruce W., Holmes, Edward C., Simmons, Cameron P., Thai, Khoa T. D., Henn, Matthew R., Zody, Michael C., Tricou, Vianney, Nguyet, Nguyen Minh, Charlebois, Patrick, Lennon, Niall J., Green, Lisa, de Vries, Peter J., Hien, Tran Tinh, Farrar, Jeremy, van Doorn, H. Rogier, de Jong, Menno D., Birren, Bruce W., Holmes, Edward C., Simmons, Cameron P.
author_sort thai, khoa t. d.
container_issue 2
container_start_page 835
container_title Journal of Virology
container_volume 86
description <jats:title>ABSTRACT</jats:title> <jats:p> Little is known about the rate at which genetic variation is generated within intrahost populations of dengue virus (DENV) and what implications this diversity has for dengue pathogenesis, disease severity, and host immunity. Previous studies of intrahost DENV variation have used a low frequency of sampling and/or experimental methods that do not fully account for errors generated through amplification and sequencing of viral RNAs. We investigated the extent and pattern of genetic diversity in sequence data in domain III (DIII) of the envelope (E) gene in serial plasma samples ( <jats:italic>n</jats:italic> = 49) taken from 17 patients infected with DENV type 1 (DENV-1), totaling some 8,458 clones. Statistically rigorous approaches were employed to account for artifactual variants resulting from amplification and sequencing, which we suggest have played a major role in previous studies of intrahost genetic variation. Accordingly, nucleotide sequence diversities of viral populations were very low, with conservative estimates of the average levels of genetic diversity ranging from 0 to 0.0013. Despite such sequence conservation, we observed clear evidence for mixed infection, with the presence of multiple phylogenetically distinct lineages present within the same host, while the presence of stop codon mutations in some samples suggests the action of complementation. In contrast to some previous studies we observed no relationship between the extent and pattern of DENV-1 genetic diversity and disease severity, immune status, or level of viremia. </jats:p>
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spelling Thai, Khoa T. D. Henn, Matthew R. Zody, Michael C. Tricou, Vianney Nguyet, Nguyen Minh Charlebois, Patrick Lennon, Niall J. Green, Lisa de Vries, Peter J. Hien, Tran Tinh Farrar, Jeremy van Doorn, H. Rogier de Jong, Menno D. Birren, Bruce W. Holmes, Edward C. Simmons, Cameron P. 0022-538X 1098-5514 American Society for Microbiology Virology Insect Science Immunology Microbiology http://dx.doi.org/10.1128/jvi.05985-11 <jats:title>ABSTRACT</jats:title> <jats:p> Little is known about the rate at which genetic variation is generated within intrahost populations of dengue virus (DENV) and what implications this diversity has for dengue pathogenesis, disease severity, and host immunity. Previous studies of intrahost DENV variation have used a low frequency of sampling and/or experimental methods that do not fully account for errors generated through amplification and sequencing of viral RNAs. We investigated the extent and pattern of genetic diversity in sequence data in domain III (DIII) of the envelope (E) gene in serial plasma samples ( <jats:italic>n</jats:italic> = 49) taken from 17 patients infected with DENV type 1 (DENV-1), totaling some 8,458 clones. Statistically rigorous approaches were employed to account for artifactual variants resulting from amplification and sequencing, which we suggest have played a major role in previous studies of intrahost genetic variation. Accordingly, nucleotide sequence diversities of viral populations were very low, with conservative estimates of the average levels of genetic diversity ranging from 0 to 0.0013. Despite such sequence conservation, we observed clear evidence for mixed infection, with the presence of multiple phylogenetically distinct lineages present within the same host, while the presence of stop codon mutations in some samples suggests the action of complementation. In contrast to some previous studies we observed no relationship between the extent and pattern of DENV-1 genetic diversity and disease severity, immune status, or level of viremia. </jats:p> High-Resolution Analysis of Intrahost Genetic Diversity in Dengue Virus Serotype 1 Infection Identifies Mixed Infections Journal of Virology
spellingShingle Thai, Khoa T. D., Henn, Matthew R., Zody, Michael C., Tricou, Vianney, Nguyet, Nguyen Minh, Charlebois, Patrick, Lennon, Niall J., Green, Lisa, de Vries, Peter J., Hien, Tran Tinh, Farrar, Jeremy, van Doorn, H. Rogier, de Jong, Menno D., Birren, Bruce W., Holmes, Edward C., Simmons, Cameron P., Journal of Virology, High-Resolution Analysis of Intrahost Genetic Diversity in Dengue Virus Serotype 1 Infection Identifies Mixed Infections, Virology, Insect Science, Immunology, Microbiology
title High-Resolution Analysis of Intrahost Genetic Diversity in Dengue Virus Serotype 1 Infection Identifies Mixed Infections
title_full High-Resolution Analysis of Intrahost Genetic Diversity in Dengue Virus Serotype 1 Infection Identifies Mixed Infections
title_fullStr High-Resolution Analysis of Intrahost Genetic Diversity in Dengue Virus Serotype 1 Infection Identifies Mixed Infections
title_full_unstemmed High-Resolution Analysis of Intrahost Genetic Diversity in Dengue Virus Serotype 1 Infection Identifies Mixed Infections
title_short High-Resolution Analysis of Intrahost Genetic Diversity in Dengue Virus Serotype 1 Infection Identifies Mixed Infections
title_sort high-resolution analysis of intrahost genetic diversity in dengue virus serotype 1 infection identifies mixed infections
title_unstemmed High-Resolution Analysis of Intrahost Genetic Diversity in Dengue Virus Serotype 1 Infection Identifies Mixed Infections
topic Virology, Insect Science, Immunology, Microbiology
url http://dx.doi.org/10.1128/jvi.05985-11