tetano
Editor, Senior Moderator
J Virol. 2010 Nov 10. [Epub ahead of print]
Higher replication efficiency of 2009 (H1N1) pandemic influenza than seasonal and avian strains: kinetics from epithelial cell culture and computational modeling.
Mitchell H, Levin D, Forrest S, Beauchemin CA, Tipper J, Knight J, Donart N, Layton RC, Pyles J, Gao P, Harrod KS, Perelson AS, Koster F.
Infectious Disease Program, Lovelace Respiratory Research Institute, Albuquerque, NM 87108; Department of Computer Science, University of New Mexico, Albuquerque, NM 87131; Department of Physics, Ryerson University, Toronto, Ontario, M5B 2K3 Canada; Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545.
Abstract
The pathogenicity and transmission of influenza A viruses are likely determined in part by replication efficiency in human cells, which is the net effect of complex virus-host interactions. H5N1 avian, H1N1 seasonal and H1N1 2009 pandemic influenza strains were compared by infecting human differentiated bronchial epithelial cells in air-liquid interface cultures at relatively low virus particle:cell ratios. Differential equation and computational models were used to characterize the in vitro kinetic behavior of the three strains. The models were calibrated by fitting experimental data in order to estimate difficult-to-measure parameters. Both models found marked differences in the relative values of p, the virion production rate per cell and R0, an index of the spread of infection through the monolayer, with the values for the strains in the rank order pandemic > seasonal > avian as expected. In the differential equation model, which treats virus and cell populations as well-mixed, R0 and p varied proportionately for all 3 strains, consistent with a primary role for productivity. In the spatially explicit computational model, R0 and p also varied proportionately except that R0 derived for the pandemic strain was reduced, consistent with constrained viral spread imposed by multiple host defenses including mucus and paracrine antiviral effects. This synergistic experimental-computational strategy provides relevant parameters for identifying and phenotyping potential pandemic strains.
PMID: 21068247 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21068247
Higher replication efficiency of 2009 (H1N1) pandemic influenza than seasonal and avian strains: kinetics from epithelial cell culture and computational modeling.
Mitchell H, Levin D, Forrest S, Beauchemin CA, Tipper J, Knight J, Donart N, Layton RC, Pyles J, Gao P, Harrod KS, Perelson AS, Koster F.
Infectious Disease Program, Lovelace Respiratory Research Institute, Albuquerque, NM 87108; Department of Computer Science, University of New Mexico, Albuquerque, NM 87131; Department of Physics, Ryerson University, Toronto, Ontario, M5B 2K3 Canada; Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545.
Abstract
The pathogenicity and transmission of influenza A viruses are likely determined in part by replication efficiency in human cells, which is the net effect of complex virus-host interactions. H5N1 avian, H1N1 seasonal and H1N1 2009 pandemic influenza strains were compared by infecting human differentiated bronchial epithelial cells in air-liquid interface cultures at relatively low virus particle:cell ratios. Differential equation and computational models were used to characterize the in vitro kinetic behavior of the three strains. The models were calibrated by fitting experimental data in order to estimate difficult-to-measure parameters. Both models found marked differences in the relative values of p, the virion production rate per cell and R0, an index of the spread of infection through the monolayer, with the values for the strains in the rank order pandemic > seasonal > avian as expected. In the differential equation model, which treats virus and cell populations as well-mixed, R0 and p varied proportionately for all 3 strains, consistent with a primary role for productivity. In the spatially explicit computational model, R0 and p also varied proportionately except that R0 derived for the pandemic strain was reduced, consistent with constrained viral spread imposed by multiple host defenses including mucus and paracrine antiviral effects. This synergistic experimental-computational strategy provides relevant parameters for identifying and phenotyping potential pandemic strains.
PMID: 21068247 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21068247