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The complex interplay between virus-encoded and host-specific pathogenicity regulators \u2013 and the relative contributions of each toward viral pathogenicity \u2013 is not well-understood.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>By analyzing a collection of lung samples from mice infected by A\/Vietnam\/1203\/2004 (H5N1; VN1203), 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 inoculation concentrations and four specific mutations in VN1203 mainly impact the magnitude and velocity of the host response kinetics, rather than specific sets of up- and down- regulated genes. We observed analogous kinetic effects using lung samples from mice infected with A\/California\/04\/2009 (H1N1), and we show that these effects correlate with morbidity and viral titer.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>We have demonstrated the importance of the kinetics of the host response to H5N1 pathogenesis and its relationship with clinical disease severity and virus replication. These kinetic properties imply that time-matched comparisons of \u2018omics profiles to viral infections give limited views to differentiate host-responses. Moreover, these results demonstrate that a fast activation of the host-response at the earliest time points post-infection is critical for protective mechanisms against fast replicating viruses.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1752-0509-7-69","type":"journal-article","created":{"date-parts":[[2013,7,29]],"date-time":"2013-07-29T14:14:30Z","timestamp":1375107270000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Specific mutations in H5N1 mainly impact the magnitude and velocity of the host response in mice"],"prefix":"10.1186","volume":"7","author":[{"given":"Nicolas","family":"Tchitchek","sequence":"first","affiliation":[]},{"given":"Amie J","family":"Eisfeld","sequence":"additional","affiliation":[]},{"given":"Jennifer","family":"Tisoncik-Go","sequence":"additional","affiliation":[]},{"given":"Laurence","family":"Josset","sequence":"additional","affiliation":[]},{"given":"Lisa E","family":"Gralinski","sequence":"additional","affiliation":[]},{"given":"Christophe","family":"B\u00e9cavin","sequence":"additional","affiliation":[]},{"given":"Susan C","family":"Tilton","sequence":"additional","affiliation":[]},{"given":"Bobbie-Jo","family":"Webb-Robertson","sequence":"additional","affiliation":[]},{"given":"Martin T","family":"Ferris","sequence":"additional","affiliation":[]},{"given":"Allison L","family":"Totura","sequence":"additional","affiliation":[]},{"given":"Chengjun","family":"Li","sequence":"additional","affiliation":[]},{"given":"Gabriele","family":"Neumann","sequence":"additional","affiliation":[]},{"given":"Thomas O","family":"Metz","sequence":"additional","affiliation":[]},{"given":"Richard D","family":"Smith","sequence":"additional","affiliation":[]},{"given":"Katrina M","family":"Waters","sequence":"additional","affiliation":[]},{"given":"Ralph","family":"Baric","sequence":"additional","affiliation":[]},{"given":"Yoshihiro","family":"Kawaoka","sequence":"additional","affiliation":[]},{"given":"Michael G","family":"Katze","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2013,7,29]]},"reference":[{"key":"1123_CR1","doi-asserted-by":"publisher","first-page":"1534","DOI":"10.1126\/science.1213362","volume":"336","author":"S Herfst","year":"2012","unstructured":"Herfst S, Schrauwen EJA, Linster M, Chutinimitkul S, de Wit E, Munster VJ, Sorrell EM, Bestebroer TM, Burke DF, Smith DJ, Rimmelzwaan GF, Osterhaus ADME, Fouchier RAM: Airborne transmission of influenza A\/H5N1 virus between ferrets. 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