author_facet Wang, Gary P.
Sherrill-Mix, Scott A.
Chang, Kyong-Mi
Quince, Chris
Bushman, Frederic D.
Wang, Gary P.
Sherrill-Mix, Scott A.
Chang, Kyong-Mi
Quince, Chris
Bushman, Frederic D.
author Wang, Gary P.
Sherrill-Mix, Scott A.
Chang, Kyong-Mi
Quince, Chris
Bushman, Frederic D.
spellingShingle Wang, Gary P.
Sherrill-Mix, Scott A.
Chang, Kyong-Mi
Quince, Chris
Bushman, Frederic D.
Journal of Virology
Hepatitis C Virus Transmission Bottlenecks Analyzed by Deep Sequencing
Virology
Insect Science
Immunology
Microbiology
author_sort wang, gary p.
spelling Wang, Gary P. Sherrill-Mix, Scott A. Chang, Kyong-Mi Quince, Chris Bushman, Frederic D. 0022-538X 1098-5514 American Society for Microbiology Virology Insect Science Immunology Microbiology http://dx.doi.org/10.1128/jvi.02271-09 <jats:title>ABSTRACT</jats:title> <jats:p>Hepatitis C virus (HCV) replication in infected patients produces large and diverse viral populations, which give rise to drug-resistant and immune escape variants. Here, we analyzed HCV populations during transmission and diversification in longitudinal and cross-sectional samples using 454/Roche pyrosequencing, in total analyzing 174,185 sequence reads. To sample diversity, four locations in the HCV genome were analyzed, ranging from high diversity (the envelope hypervariable region 1 [HVR1]) to almost no diversity (the 5′ untranslated region [UTR]). For three longitudinal samples for which early time points were available, we found that only 1 to 4 viral variants were present, suggesting that productive infection was initiated by a very small number of HCV particles. Sequence diversity accumulated subsequently, with the 5′ UTR showing almost no diversification while the envelope HVR1 showed &gt;100 variants in some subjects. Calculation of the transmission probability for only a single variant, taking into account the measured population structure within patients, confirmed initial infection by one or a few viral particles. These findings provide the most detailed sequence-based analysis of HCV transmission bottlenecks to date. The analytical methods described here are broadly applicable to studies of viral diversity using deep sequencing.</jats:p> Hepatitis C Virus Transmission Bottlenecks Analyzed by Deep Sequencing Journal of Virology
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title Hepatitis C Virus Transmission Bottlenecks Analyzed by Deep Sequencing
title_unstemmed Hepatitis C Virus Transmission Bottlenecks Analyzed by Deep Sequencing
title_full Hepatitis C Virus Transmission Bottlenecks Analyzed by Deep Sequencing
title_fullStr Hepatitis C Virus Transmission Bottlenecks Analyzed by Deep Sequencing
title_full_unstemmed Hepatitis C Virus Transmission Bottlenecks Analyzed by Deep Sequencing
title_short Hepatitis C Virus Transmission Bottlenecks Analyzed by Deep Sequencing
title_sort hepatitis c virus transmission bottlenecks analyzed by deep sequencing
topic Virology
Insect Science
Immunology
Microbiology
url http://dx.doi.org/10.1128/jvi.02271-09
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description <jats:title>ABSTRACT</jats:title> <jats:p>Hepatitis C virus (HCV) replication in infected patients produces large and diverse viral populations, which give rise to drug-resistant and immune escape variants. Here, we analyzed HCV populations during transmission and diversification in longitudinal and cross-sectional samples using 454/Roche pyrosequencing, in total analyzing 174,185 sequence reads. To sample diversity, four locations in the HCV genome were analyzed, ranging from high diversity (the envelope hypervariable region 1 [HVR1]) to almost no diversity (the 5′ untranslated region [UTR]). For three longitudinal samples for which early time points were available, we found that only 1 to 4 viral variants were present, suggesting that productive infection was initiated by a very small number of HCV particles. Sequence diversity accumulated subsequently, with the 5′ UTR showing almost no diversification while the envelope HVR1 showed &gt;100 variants in some subjects. Calculation of the transmission probability for only a single variant, taking into account the measured population structure within patients, confirmed initial infection by one or a few viral particles. These findings provide the most detailed sequence-based analysis of HCV transmission bottlenecks to date. The analytical methods described here are broadly applicable to studies of viral diversity using deep sequencing.</jats:p>
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author Wang, Gary P., Sherrill-Mix, Scott A., Chang, Kyong-Mi, Quince, Chris, Bushman, Frederic D.
author_facet Wang, Gary P., Sherrill-Mix, Scott A., Chang, Kyong-Mi, Quince, Chris, Bushman, Frederic D., Wang, Gary P., Sherrill-Mix, Scott A., Chang, Kyong-Mi, Quince, Chris, Bushman, Frederic D.
author_sort wang, gary p.
container_issue 12
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description <jats:title>ABSTRACT</jats:title> <jats:p>Hepatitis C virus (HCV) replication in infected patients produces large and diverse viral populations, which give rise to drug-resistant and immune escape variants. Here, we analyzed HCV populations during transmission and diversification in longitudinal and cross-sectional samples using 454/Roche pyrosequencing, in total analyzing 174,185 sequence reads. To sample diversity, four locations in the HCV genome were analyzed, ranging from high diversity (the envelope hypervariable region 1 [HVR1]) to almost no diversity (the 5′ untranslated region [UTR]). For three longitudinal samples for which early time points were available, we found that only 1 to 4 viral variants were present, suggesting that productive infection was initiated by a very small number of HCV particles. Sequence diversity accumulated subsequently, with the 5′ UTR showing almost no diversification while the envelope HVR1 showed &gt;100 variants in some subjects. Calculation of the transmission probability for only a single variant, taking into account the measured population structure within patients, confirmed initial infection by one or a few viral particles. These findings provide the most detailed sequence-based analysis of HCV transmission bottlenecks to date. The analytical methods described here are broadly applicable to studies of viral diversity using deep sequencing.</jats:p>
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spelling Wang, Gary P. Sherrill-Mix, Scott A. Chang, Kyong-Mi Quince, Chris Bushman, Frederic D. 0022-538X 1098-5514 American Society for Microbiology Virology Insect Science Immunology Microbiology http://dx.doi.org/10.1128/jvi.02271-09 <jats:title>ABSTRACT</jats:title> <jats:p>Hepatitis C virus (HCV) replication in infected patients produces large and diverse viral populations, which give rise to drug-resistant and immune escape variants. Here, we analyzed HCV populations during transmission and diversification in longitudinal and cross-sectional samples using 454/Roche pyrosequencing, in total analyzing 174,185 sequence reads. To sample diversity, four locations in the HCV genome were analyzed, ranging from high diversity (the envelope hypervariable region 1 [HVR1]) to almost no diversity (the 5′ untranslated region [UTR]). For three longitudinal samples for which early time points were available, we found that only 1 to 4 viral variants were present, suggesting that productive infection was initiated by a very small number of HCV particles. Sequence diversity accumulated subsequently, with the 5′ UTR showing almost no diversification while the envelope HVR1 showed &gt;100 variants in some subjects. Calculation of the transmission probability for only a single variant, taking into account the measured population structure within patients, confirmed initial infection by one or a few viral particles. These findings provide the most detailed sequence-based analysis of HCV transmission bottlenecks to date. The analytical methods described here are broadly applicable to studies of viral diversity using deep sequencing.</jats:p> Hepatitis C Virus Transmission Bottlenecks Analyzed by Deep Sequencing Journal of Virology
spellingShingle Wang, Gary P., Sherrill-Mix, Scott A., Chang, Kyong-Mi, Quince, Chris, Bushman, Frederic D., Journal of Virology, Hepatitis C Virus Transmission Bottlenecks Analyzed by Deep Sequencing, Virology, Insect Science, Immunology, Microbiology
title Hepatitis C Virus Transmission Bottlenecks Analyzed by Deep Sequencing
title_full Hepatitis C Virus Transmission Bottlenecks Analyzed by Deep Sequencing
title_fullStr Hepatitis C Virus Transmission Bottlenecks Analyzed by Deep Sequencing
title_full_unstemmed Hepatitis C Virus Transmission Bottlenecks Analyzed by Deep Sequencing
title_short Hepatitis C Virus Transmission Bottlenecks Analyzed by Deep Sequencing
title_sort hepatitis c virus transmission bottlenecks analyzed by deep sequencing
title_unstemmed Hepatitis C Virus Transmission Bottlenecks Analyzed by Deep Sequencing
topic Virology, Insect Science, Immunology, Microbiology
url http://dx.doi.org/10.1128/jvi.02271-09