Quantifying the fitness advantage of polymerase substitutions in Influenza A/H7N9 viruses during adaptation to humans.
Adaptation of zoonotic influenza viruses towards efficient human-to-human transmissibility is a substantial public health concern. The recently emerged A/H7N9 influenza viruses in China provide an opportunity for quantitative studies of host-adaptation, as human-adaptive substitutions in the PB2 gen...
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0076047&type=printable |
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| author | Judith M Fonville David F Burke Nicola S Lewis Leah C Katzelnick Colin A Russell |
| author_facet | Judith M Fonville David F Burke Nicola S Lewis Leah C Katzelnick Colin A Russell |
| author_sort | Judith M Fonville |
| collection | DOAJ |
| description | Adaptation of zoonotic influenza viruses towards efficient human-to-human transmissibility is a substantial public health concern. The recently emerged A/H7N9 influenza viruses in China provide an opportunity for quantitative studies of host-adaptation, as human-adaptive substitutions in the PB2 gene of the virus have been found in all sequenced human strains, while these substitutions have not been detected in any non-human A/H7N9 sequences. Given the currently available information, this observation suggests that the human-adaptive PB2 substitution might confer a fitness advantage to the virus in these human hosts that allows it to rise to proportions detectable by consensus sequencing over the course of a single human infection. We use a mathematical model of within-host virus evolution to estimate the fitness advantage required for a substitution to reach predominance in a single infection as a function of the duration of infection and the fraction of mutant present in the virus population that initially infects a human. The modeling results provide an estimate of the lower bound for the fitness advantage of this adaptive substitution in the currently sequenced A/H7N9 viruses. This framework can be more generally used to quantitatively estimate fitness advantages of adaptive substitutions based on the within-host prevalence of mutations. Such estimates are critical for models of cross-species transmission and host-adaptation of influenza virus infections. |
| format | Article |
| id | doaj-art-1ae933ec45ee46278addf58d339d047f |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-1ae933ec45ee46278addf58d339d047f2025-08-20T02:35:36ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0189e7604710.1371/journal.pone.0076047Quantifying the fitness advantage of polymerase substitutions in Influenza A/H7N9 viruses during adaptation to humans.Judith M FonvilleDavid F BurkeNicola S LewisLeah C KatzelnickColin A RussellAdaptation of zoonotic influenza viruses towards efficient human-to-human transmissibility is a substantial public health concern. The recently emerged A/H7N9 influenza viruses in China provide an opportunity for quantitative studies of host-adaptation, as human-adaptive substitutions in the PB2 gene of the virus have been found in all sequenced human strains, while these substitutions have not been detected in any non-human A/H7N9 sequences. Given the currently available information, this observation suggests that the human-adaptive PB2 substitution might confer a fitness advantage to the virus in these human hosts that allows it to rise to proportions detectable by consensus sequencing over the course of a single human infection. We use a mathematical model of within-host virus evolution to estimate the fitness advantage required for a substitution to reach predominance in a single infection as a function of the duration of infection and the fraction of mutant present in the virus population that initially infects a human. The modeling results provide an estimate of the lower bound for the fitness advantage of this adaptive substitution in the currently sequenced A/H7N9 viruses. This framework can be more generally used to quantitatively estimate fitness advantages of adaptive substitutions based on the within-host prevalence of mutations. Such estimates are critical for models of cross-species transmission and host-adaptation of influenza virus infections.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0076047&type=printable |
| spellingShingle | Judith M Fonville David F Burke Nicola S Lewis Leah C Katzelnick Colin A Russell Quantifying the fitness advantage of polymerase substitutions in Influenza A/H7N9 viruses during adaptation to humans. PLoS ONE |
| title | Quantifying the fitness advantage of polymerase substitutions in Influenza A/H7N9 viruses during adaptation to humans. |
| title_full | Quantifying the fitness advantage of polymerase substitutions in Influenza A/H7N9 viruses during adaptation to humans. |
| title_fullStr | Quantifying the fitness advantage of polymerase substitutions in Influenza A/H7N9 viruses during adaptation to humans. |
| title_full_unstemmed | Quantifying the fitness advantage of polymerase substitutions in Influenza A/H7N9 viruses during adaptation to humans. |
| title_short | Quantifying the fitness advantage of polymerase substitutions in Influenza A/H7N9 viruses during adaptation to humans. |
| title_sort | quantifying the fitness advantage of polymerase substitutions in influenza a h7n9 viruses during adaptation to humans |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0076047&type=printable |
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