Assessing the in vitro fitness of an oseltamivir-resistant seasonal A/H1N1 influenza strain using a mathematical model.
In 2007, the A/Brisbane/59/2007 (H1N1) seasonal influenza virus strain acquired the oseltamivir-resistance mutation H275Y in its neuraminidase (NA) gene. Although previous studies had demonstrated that this mutation impaired the replication capacity of the influenza virus in vitro and in vivo, the A...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-03-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3063785?pdf=render |
| _version_ | 1819010079744065536 |
|---|---|
| author | Benjamin P Holder Philippe Simon Laura E Liao Yacine Abed Xavier Bouhy Catherine A A Beauchemin Guy Boivin |
| author_facet | Benjamin P Holder Philippe Simon Laura E Liao Yacine Abed Xavier Bouhy Catherine A A Beauchemin Guy Boivin |
| author_sort | Benjamin P Holder |
| collection | DOAJ |
| description | In 2007, the A/Brisbane/59/2007 (H1N1) seasonal influenza virus strain acquired the oseltamivir-resistance mutation H275Y in its neuraminidase (NA) gene. Although previous studies had demonstrated that this mutation impaired the replication capacity of the influenza virus in vitro and in vivo, the A/Brisbane/59/2007 H275Y oseltamivir-resistant mutant completely out-competed the wild-type (WT) strain and was, in the 2008-2009 influenza season, the primary A/H1N1 circulating strain. Using a combination of plaque and viral yield assays, and a simple mathematical model, approximate values were extracted for two basic viral kinetics parameters of the in vitro infection. In the ST6GalI-MDCK cell line, the latent infection period (i.e., the time for a newly infected cell to start releasing virions) was found to be 1-3 h for the WT strain and more than 7 h for the H275Y mutant. The infecting time (i.e., the time for a single infectious cell to cause the infection of another one) was between 30 and 80 min for the WT, and less than 5 min for the H275Y mutant. Single-cycle viral yield experiments have provided qualitative confirmation of these findings. These results, though preliminary, suggest that the increased fitness success of the A/Brisbane/59/2007 H275Y mutant may be due to increased infectivity compensating for an impaired or delayed viral release, and are consistent with recent evidence for the mechanistic origins of fitness reduction and recovery in NA expression. The method applied here can reconcile seemingly contradictory results from the plaque and yield assays as two complementary views of replication kinetics, with both required to fully capture a strain's fitness. |
| first_indexed | 2024-12-21T01:06:34Z |
| format | Article |
| id | doaj.art-4a624d42d48b4fee8c2084f760f0434f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T01:06:34Z |
| publishDate | 2011-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-4a624d42d48b4fee8c2084f760f0434f2022-12-21T19:21:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-03-0163e1476710.1371/journal.pone.0014767Assessing the in vitro fitness of an oseltamivir-resistant seasonal A/H1N1 influenza strain using a mathematical model.Benjamin P HolderPhilippe SimonLaura E LiaoYacine AbedXavier BouhyCatherine A A BeaucheminGuy BoivinIn 2007, the A/Brisbane/59/2007 (H1N1) seasonal influenza virus strain acquired the oseltamivir-resistance mutation H275Y in its neuraminidase (NA) gene. Although previous studies had demonstrated that this mutation impaired the replication capacity of the influenza virus in vitro and in vivo, the A/Brisbane/59/2007 H275Y oseltamivir-resistant mutant completely out-competed the wild-type (WT) strain and was, in the 2008-2009 influenza season, the primary A/H1N1 circulating strain. Using a combination of plaque and viral yield assays, and a simple mathematical model, approximate values were extracted for two basic viral kinetics parameters of the in vitro infection. In the ST6GalI-MDCK cell line, the latent infection period (i.e., the time for a newly infected cell to start releasing virions) was found to be 1-3 h for the WT strain and more than 7 h for the H275Y mutant. The infecting time (i.e., the time for a single infectious cell to cause the infection of another one) was between 30 and 80 min for the WT, and less than 5 min for the H275Y mutant. Single-cycle viral yield experiments have provided qualitative confirmation of these findings. These results, though preliminary, suggest that the increased fitness success of the A/Brisbane/59/2007 H275Y mutant may be due to increased infectivity compensating for an impaired or delayed viral release, and are consistent with recent evidence for the mechanistic origins of fitness reduction and recovery in NA expression. The method applied here can reconcile seemingly contradictory results from the plaque and yield assays as two complementary views of replication kinetics, with both required to fully capture a strain's fitness.http://europepmc.org/articles/PMC3063785?pdf=render |
| spellingShingle | Benjamin P Holder Philippe Simon Laura E Liao Yacine Abed Xavier Bouhy Catherine A A Beauchemin Guy Boivin Assessing the in vitro fitness of an oseltamivir-resistant seasonal A/H1N1 influenza strain using a mathematical model. PLoS ONE |
| title | Assessing the in vitro fitness of an oseltamivir-resistant seasonal A/H1N1 influenza strain using a mathematical model. |
| title_full | Assessing the in vitro fitness of an oseltamivir-resistant seasonal A/H1N1 influenza strain using a mathematical model. |
| title_fullStr | Assessing the in vitro fitness of an oseltamivir-resistant seasonal A/H1N1 influenza strain using a mathematical model. |
| title_full_unstemmed | Assessing the in vitro fitness of an oseltamivir-resistant seasonal A/H1N1 influenza strain using a mathematical model. |
| title_short | Assessing the in vitro fitness of an oseltamivir-resistant seasonal A/H1N1 influenza strain using a mathematical model. |
| title_sort | assessing the in vitro fitness of an oseltamivir resistant seasonal a h1n1 influenza strain using a mathematical model |
| url | http://europepmc.org/articles/PMC3063785?pdf=render |
| work_keys_str_mv | AT benjaminpholder assessingtheinvitrofitnessofanoseltamivirresistantseasonalah1n1influenzastrainusingamathematicalmodel AT philippesimon assessingtheinvitrofitnessofanoseltamivirresistantseasonalah1n1influenzastrainusingamathematicalmodel AT lauraeliao assessingtheinvitrofitnessofanoseltamivirresistantseasonalah1n1influenzastrainusingamathematicalmodel AT yacineabed assessingtheinvitrofitnessofanoseltamivirresistantseasonalah1n1influenzastrainusingamathematicalmodel AT xavierbouhy assessingtheinvitrofitnessofanoseltamivirresistantseasonalah1n1influenzastrainusingamathematicalmodel AT catherineaabeauchemin assessingtheinvitrofitnessofanoseltamivirresistantseasonalah1n1influenzastrainusingamathematicalmodel AT guyboivin assessingtheinvitrofitnessofanoseltamivirresistantseasonalah1n1influenzastrainusingamathematicalmodel |