Modeling host responses in ferrets during A/California/07/2009 influenza infection

Thomas Rowe; Alberto J. León; Corey J. Crevar; Donald M. Carter; Luoling Xu; Longsi Ran; Yuan Fang; Cheryl M. Cameron; Mark J. Cameron; David Banner; Derek C.K. Ng; Ran Ran; Heather K. Weirback; Clayton A. Wiley; David J. Kelvin; Ted M. Ross

doi:10.1016/j.virol.2010.02.020

Modeling host responses in ferrets during A/California/07/2009 influenza infection

Thomas Rowe, Alberto J. León, Corey J. Crevar, Donald M. Carter, Luoling Xu, Longsi Ran, Yuan Fang, Cheryl M. Cameron, Mark J. Cameron, David Banner, Derek C.K. Ng, Ran Ran, Heather K. Weirback, Clayton A. Wiley, David J. Kelvin, Ted M. Ross

Research output: Contribution to journal › Article › peer-review

92 Citations (Scopus)

Abstract

Immune responses during infection with pandemic H1N1 2009 influenza A virus (2009-H1N1) are still poorly understood. Using an experimental infection model in ferrets, we examined the pathological features and characterized the host immune responses by using microarray analysis, during infection with 2009-H1N1 A/California/07/2009 and seasonal A/Brisbane/59/2007. Chemokines CCL2, CCL8, CXCL7 and CXCL10 along with the majority of interferon-stimulated genes were expressed early, correlated to lung pathology, and abruptly decreased expression on day 7 following infection of A/California/07/2009. Interestingly, the drop in innate immune gene expression was replaced by a significant increase of the adaptive immune genes for granzymes and immunoglobulins. Serum anti-influenza antibodies were first observed on day 7, commensurate with the viral clearance. We propose that lung pathology in humans occurs during the innate phase of host immunity and a delay or failure to switch to the adaptive phase may contribute to morbidity and mortality during severe 2009-H1N1 infections.

Original language	English
Pages (from-to)	257-265
Number of pages	9
Journal	Virology
Volume	401
Issue number	2
DOIs	https://doi.org/10.1016/j.virol.2010.02.020
Publication status	Published - Jun 2010
Externally published	Yes

Bibliographical note

Funding Information:
This research was supported by National Institute of Health Award U01AI077771 to C.A.W and T.M.R. This research was also supported by the NIH-NIAD grant N01A130067 , CIHR grant ( Funding ref.#99016 ) and the Li Ka-Shing Foundation of Canada to DJK . The Canada–China Training Course in Emerging Infectious Disease, Shantou Medical College was supported by the Li Ka-Shing Foundation Canada.

ASJC Scopus Subject Areas

Virology

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10.1016/j.virol.2010.02.020

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Rowe, T., León, A. J., Crevar, C. J., Carter, D. M., Xu, L., Ran, L., Fang, Y., Cameron, C. M., Cameron, M. J., Banner, D., Ng, D. C. K., Ran, R., Weirback, H. K., Wiley, C. A., Kelvin, D. J., & Ross, T. M. (2010). Modeling host responses in ferrets during A/California/07/2009 influenza infection. Virology, 401(2), 257-265. https://doi.org/10.1016/j.virol.2010.02.020

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title = "Modeling host responses in ferrets during A/California/07/2009 influenza infection",

abstract = "Immune responses during infection with pandemic H1N1 2009 influenza A virus (2009-H1N1) are still poorly understood. Using an experimental infection model in ferrets, we examined the pathological features and characterized the host immune responses by using microarray analysis, during infection with 2009-H1N1 A/California/07/2009 and seasonal A/Brisbane/59/2007. Chemokines CCL2, CCL8, CXCL7 and CXCL10 along with the majority of interferon-stimulated genes were expressed early, correlated to lung pathology, and abruptly decreased expression on day 7 following infection of A/California/07/2009. Interestingly, the drop in innate immune gene expression was replaced by a significant increase of the adaptive immune genes for granzymes and immunoglobulins. Serum anti-influenza antibodies were first observed on day 7, commensurate with the viral clearance. We propose that lung pathology in humans occurs during the innate phase of host immunity and a delay or failure to switch to the adaptive phase may contribute to morbidity and mortality during severe 2009-H1N1 infections.",

author = "Thomas Rowe and Le{\'o}n, {Alberto J.} and Crevar, {Corey J.} and Carter, {Donald M.} and Luoling Xu and Longsi Ran and Yuan Fang and Cameron, {Cheryl M.} and Cameron, {Mark J.} and David Banner and Ng, {Derek C.K.} and Ran Ran and Weirback, {Heather K.} and Wiley, {Clayton A.} and Kelvin, {David J.} and Ross, {Ted M.}",

note = "Funding Information: This research was supported by National Institute of Health Award U01AI077771 to C.A.W and T.M.R. This research was also supported by the NIH-NIAD grant N01A130067 , CIHR grant ( Funding ref.#99016 ) and the Li Ka-Shing Foundation of Canada to DJK . The Canada–China Training Course in Emerging Infectious Disease, Shantou Medical College was supported by the Li Ka-Shing Foundation Canada. ",

year = "2010",

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doi = "10.1016/j.virol.2010.02.020",

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AU - Rowe, Thomas

AU - León, Alberto J.

AU - Crevar, Corey J.

AU - Carter, Donald M.

AU - Xu, Luoling

AU - Ran, Longsi

AU - Fang, Yuan

AU - Cameron, Cheryl M.

AU - Cameron, Mark J.

AU - Banner, David

AU - Ng, Derek C.K.

AU - Ran, Ran

AU - Weirback, Heather K.

AU - Wiley, Clayton A.

AU - Kelvin, David J.

AU - Ross, Ted M.

N1 - Funding Information: This research was supported by National Institute of Health Award U01AI077771 to C.A.W and T.M.R. This research was also supported by the NIH-NIAD grant N01A130067 , CIHR grant ( Funding ref.#99016 ) and the Li Ka-Shing Foundation of Canada to DJK . The Canada–China Training Course in Emerging Infectious Disease, Shantou Medical College was supported by the Li Ka-Shing Foundation Canada.

PY - 2010/6

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N2 - Immune responses during infection with pandemic H1N1 2009 influenza A virus (2009-H1N1) are still poorly understood. Using an experimental infection model in ferrets, we examined the pathological features and characterized the host immune responses by using microarray analysis, during infection with 2009-H1N1 A/California/07/2009 and seasonal A/Brisbane/59/2007. Chemokines CCL2, CCL8, CXCL7 and CXCL10 along with the majority of interferon-stimulated genes were expressed early, correlated to lung pathology, and abruptly decreased expression on day 7 following infection of A/California/07/2009. Interestingly, the drop in innate immune gene expression was replaced by a significant increase of the adaptive immune genes for granzymes and immunoglobulins. Serum anti-influenza antibodies were first observed on day 7, commensurate with the viral clearance. We propose that lung pathology in humans occurs during the innate phase of host immunity and a delay or failure to switch to the adaptive phase may contribute to morbidity and mortality during severe 2009-H1N1 infections.

AB - Immune responses during infection with pandemic H1N1 2009 influenza A virus (2009-H1N1) are still poorly understood. Using an experimental infection model in ferrets, we examined the pathological features and characterized the host immune responses by using microarray analysis, during infection with 2009-H1N1 A/California/07/2009 and seasonal A/Brisbane/59/2007. Chemokines CCL2, CCL8, CXCL7 and CXCL10 along with the majority of interferon-stimulated genes were expressed early, correlated to lung pathology, and abruptly decreased expression on day 7 following infection of A/California/07/2009. Interestingly, the drop in innate immune gene expression was replaced by a significant increase of the adaptive immune genes for granzymes and immunoglobulins. Serum anti-influenza antibodies were first observed on day 7, commensurate with the viral clearance. We propose that lung pathology in humans occurs during the innate phase of host immunity and a delay or failure to switch to the adaptive phase may contribute to morbidity and mortality during severe 2009-H1N1 infections.

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Modeling host responses in ferrets during A/California/07/2009 influenza infection

Abstract

Bibliographical note

ASJC Scopus Subject Areas

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