tetano
Editor, Senior Moderator
J Virol. 2012 Jul 25. [Epub ahead of print]
The H275Y neuraminidase mutation of the pandemic A/H1N1 virus lengthens the eclipse phase and reduces viral output of infected cells, potentially compromising fitness in ferrets.
Pinilla LT, Holder BP, Abed Y, Boivin G, Beauchemin CA.
Source
Infectious Disease Research Centre, CHUQ-CHUL and Laval University, Qu?bec, QC, Canada.
Abstract
The H275Y amino acid substitution of the neuraminidase (NA) gene is the most common mutation conferring oseltamivir resistance in the N1 subtype of influenza. Using a mathematical model to analyze a set of in vitro experiments that allow for the full characterization of the viral replication cycle, we show that the primary effects of the H275Y substitution on the pandemic H1N1 (H1N1pdm09) strain are to lengthen the mean eclipse phase of infected cells (from 6.6 h to 9.1 h) and decrease (by 7-fold) the viral burst size, i.e., the total number of virions produced per cell. We also find, however, that the infectious unit to particle ratio of the H275Y mutant strain is 12-fold higher than that of the oseltamivir-susceptible strain (0.19 vs. 0.016 per RNA copy). A parallel analysis of the H275Y mutation in the prior seasonal A/Brisbane/59/2007 background shows similar changes in the infection kinetics parameters, but in this background the H275Y mutation also allows the mutant to infect cells five times more rapidly. Competitive mixed-strain infections in vitro, where the susceptible and resistant H1N1pdm09 strains must compete for cells, are characterized by higher viral production for the susceptible strain, but suggest equivalent fractions of infected cells in the culture. In ferrets, however, the mutant strain appears to suffer a delay in its infection of the respiratory tract which allows the susceptible strain to dominate mixed-strain infections.
PMID:
22837199
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22837199
The H275Y neuraminidase mutation of the pandemic A/H1N1 virus lengthens the eclipse phase and reduces viral output of infected cells, potentially compromising fitness in ferrets.
Pinilla LT, Holder BP, Abed Y, Boivin G, Beauchemin CA.
Source
Infectious Disease Research Centre, CHUQ-CHUL and Laval University, Qu?bec, QC, Canada.
Abstract
The H275Y amino acid substitution of the neuraminidase (NA) gene is the most common mutation conferring oseltamivir resistance in the N1 subtype of influenza. Using a mathematical model to analyze a set of in vitro experiments that allow for the full characterization of the viral replication cycle, we show that the primary effects of the H275Y substitution on the pandemic H1N1 (H1N1pdm09) strain are to lengthen the mean eclipse phase of infected cells (from 6.6 h to 9.1 h) and decrease (by 7-fold) the viral burst size, i.e., the total number of virions produced per cell. We also find, however, that the infectious unit to particle ratio of the H275Y mutant strain is 12-fold higher than that of the oseltamivir-susceptible strain (0.19 vs. 0.016 per RNA copy). A parallel analysis of the H275Y mutation in the prior seasonal A/Brisbane/59/2007 background shows similar changes in the infection kinetics parameters, but in this background the H275Y mutation also allows the mutant to infect cells five times more rapidly. Competitive mixed-strain infections in vitro, where the susceptible and resistant H1N1pdm09 strains must compete for cells, are characterized by higher viral production for the susceptible strain, but suggest equivalent fractions of infected cells in the culture. In ferrets, however, the mutant strain appears to suffer a delay in its infection of the respiratory tract which allows the susceptible strain to dominate mixed-strain infections.
PMID:
22837199
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22837199