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Title: Specific Mutations in H5N1 Mainly Impact the Magnitude and Velocity of the Host Response in Mice

Abstract

Influenza infection causes respiratory disease that can lead to death. The complex interplay between virus-encoded and host-specific pathogenicity regulators is not well-understood. By analyzing a collection of mouse lung samples infected by A/Vietnam/1203/2004 (H5N1; VN1203) influenza, we characterized a signature of transcripts and proteins associated with the kinetics of the host response. Using a new geometrical representation method and two criteria, we show that infection concentrations and four specific mutations in VN1203 mainly impact on the magnitude and velocity of the host response kinetics, rather than on specific sets of genes up- and down-regulated. We observed similar kinetic effects using A/California/04/2009 (H1N1)-infected samples, and we show that these effects correlate with mice morbidity and viral titer measurements. Speed and extent of changes in the host response between days 1 and 2 post-infection were attenuated for each VN1203 mutant compared to the wild-type, except for PB1-F2 deletion at a high dose, which was associated with high virulence. This indicates that the host response in that time frame is critical and that immunomodulatory therapeutics should specifically be applied during the early days post-infection.

Authors:
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Environmental Molecular Sciences Lab. (EMSL)
Sponsoring Org.:
USDOE
OSTI Identifier:
1094939
Report Number(s):
PNNL-SA-94011
47092; 600306000
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Journal Name:
BMC Systems Biology, 7:Article No. 69
Additional Journal Information:
Journal Name: BMC Systems Biology, 7:Article No. 69
Country of Publication:
United States
Language:
English
Subject:
Environmental Molecular Sciences Laboratory

Citation Formats

Tchitchek, Nicholas, Eisfeld, Amie J., Tisoncik-Go, Jennifer, Josset, Laurence, Gralinski, Lisa, Becavin, Christophe, Tilton, Susan C., Webb-Robertson, Bobbie-Jo M., Ferris, Martin T., Totura, Allison L., Li, Chengjun, Neumann, Gabriele, Metz, Thomas O., Smith, Richard D., Waters, Katrina M., Baric, Ralph, Kawaoka, Yoshihiro, and Katze, Michael G. Specific Mutations in H5N1 Mainly Impact the Magnitude and Velocity of the Host Response in Mice. United States: N. p., 2013. Web. doi:10.1186/1752-0509-7-69.
Tchitchek, Nicholas, Eisfeld, Amie J., Tisoncik-Go, Jennifer, Josset, Laurence, Gralinski, Lisa, Becavin, Christophe, Tilton, Susan C., Webb-Robertson, Bobbie-Jo M., Ferris, Martin T., Totura, Allison L., Li, Chengjun, Neumann, Gabriele, Metz, Thomas O., Smith, Richard D., Waters, Katrina M., Baric, Ralph, Kawaoka, Yoshihiro, & Katze, Michael G. Specific Mutations in H5N1 Mainly Impact the Magnitude and Velocity of the Host Response in Mice. United States. https://doi.org/10.1186/1752-0509-7-69
Tchitchek, Nicholas, Eisfeld, Amie J., Tisoncik-Go, Jennifer, Josset, Laurence, Gralinski, Lisa, Becavin, Christophe, Tilton, Susan C., Webb-Robertson, Bobbie-Jo M., Ferris, Martin T., Totura, Allison L., Li, Chengjun, Neumann, Gabriele, Metz, Thomas O., Smith, Richard D., Waters, Katrina M., Baric, Ralph, Kawaoka, Yoshihiro, and Katze, Michael G. 2013. "Specific Mutations in H5N1 Mainly Impact the Magnitude and Velocity of the Host Response in Mice". United States. https://doi.org/10.1186/1752-0509-7-69.
@article{osti_1094939,
title = {Specific Mutations in H5N1 Mainly Impact the Magnitude and Velocity of the Host Response in Mice},
author = {Tchitchek, Nicholas and Eisfeld, Amie J. and Tisoncik-Go, Jennifer and Josset, Laurence and Gralinski, Lisa and Becavin, Christophe and Tilton, Susan C. and Webb-Robertson, Bobbie-Jo M. and Ferris, Martin T. and Totura, Allison L. and Li, Chengjun and Neumann, Gabriele and Metz, Thomas O. and Smith, Richard D. and Waters, Katrina M. and Baric, Ralph and Kawaoka, Yoshihiro and Katze, Michael G.},
abstractNote = {Influenza infection causes respiratory disease that can lead to death. The complex interplay between virus-encoded and host-specific pathogenicity regulators is not well-understood. By analyzing a collection of mouse lung samples infected by A/Vietnam/1203/2004 (H5N1; VN1203) influenza, we characterized a signature of transcripts and proteins associated with the kinetics of the host response. Using a new geometrical representation method and two criteria, we show that infection concentrations and four specific mutations in VN1203 mainly impact on the magnitude and velocity of the host response kinetics, rather than on specific sets of genes up- and down-regulated. We observed similar kinetic effects using A/California/04/2009 (H1N1)-infected samples, and we show that these effects correlate with mice morbidity and viral titer measurements. Speed and extent of changes in the host response between days 1 and 2 post-infection were attenuated for each VN1203 mutant compared to the wild-type, except for PB1-F2 deletion at a high dose, which was associated with high virulence. This indicates that the host response in that time frame is critical and that immunomodulatory therapeutics should specifically be applied during the early days post-infection.},
doi = {10.1186/1752-0509-7-69},
url = {https://www.osti.gov/biblio/1094939}, journal = {BMC Systems Biology, 7:Article No. 69},
number = ,
volume = ,
place = {United States},
year = {Mon Jul 29 00:00:00 EDT 2013},
month = {Mon Jul 29 00:00:00 EDT 2013}
}