Lack of group X secreted phospholipase A2 increases survival following pandemic H1N1 influenza infection

Alyson A. Kelvin; Norbert Degousee; David Banner; Eva Stefanski; Alberto J. León; Denis Angoulvant; Stéphane G. Paquette; Stephen S.H. Huang; Ali Danesh; Clinton S. Robbins; Hossein Noyan; Mansoor Husain; Gerard Lambeau; Michael Gelb; David J. Kelvin; Barry B. Rubin

doi:10.1016/j.virol.2014.01.030

Lack of group X secreted phospholipase A₂ increases survival following pandemic H1N1 influenza infection

Alyson A. Kelvin, Norbert Degousee, David Banner, Eva Stefanski, Alberto J. León, Denis Angoulvant, Stéphane G. Paquette, Stephen S.H. Huang, Ali Danesh, Clinton S. Robbins, Hossein Noyan, Mansoor Husain, Gerard Lambeau, Michael Gelb, David J. Kelvin, Barry B. Rubin

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

21 Citations (Scopus)

Abstract

The role of Group X secreted phospholipase A₂ (GX-sPLA₂) during influenza infection has not been previously investigated. We examined the role of GX-sPLA₂ during H1N1 pandemic influenza infection in a GX-sPLA₂ gene targeted mouse (GX^-/-) model and found that survival after infection was significantly greater in GX^-/- mice than in GX^+/+ mice. Downstream products of GX-sPLA₂ activity, PGD₂, PGE₂, LTB₄, cysteinyl leukotrienes and Lipoxin A₄ were significantly lower in GX^-/- mice BAL fluid. Lung microarray analysis identified an earlier and more robust induction of T and B cell associated genes in GX^-/- mice. Based on the central role of sPLA₂ enzymes as key initiators of inflammatory processes, we propose that activation of GX-sPLA₂ during H1N1pdm infection is an early step of pulmonary inflammation and its inhibition increases adaptive immunity and improves survival. Our findings suggest that GX-sPLA₂ may be a potential therapeutic target during influenza.

Original language	English
Pages (from-to)	78-92
Number of pages	15
Journal	Virology
Volume	454-455
Issue number	1
DOIs	https://doi.org/10.1016/j.virol.2014.01.030
Publication status	Published - Apr 2014
Externally published	Yes

Bibliographical note

Funding Information:
A/Mexico/4108/2009 was obtained through the Influenza Reagent Resource, Influenza Division, WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza, Centers for Disease Control and Prevention, Atlanta, GA, USA. We thank the Li Ka-Shing Foundation of Canada, Immune Diagnostics & Research, Shantou University Medical College, NIH (Grant R37 HL36235 ), NIH 1U01AI11598-01 Subaward no. 0038591(123721-3) to the support of this study and the Canadian Institutes of Health Research (CIHR) (Grant MOP 126205 (Dr. Rubin)) for the support of this study. We thank the staff from the Animal Resource Center of University Health Network for their help with the animal experiments.

ASJC Scopus Subject Areas

Virology

PubMed: MeSH publication types

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Access to Document

10.1016/j.virol.2014.01.030

Cite this

Kelvin, A. A., Degousee, N., Banner, D., Stefanski, E., León, A. J., Angoulvant, D., Paquette, S. G., Huang, S. S. H., Danesh, A., Robbins, C. S., Noyan, H., Husain, M., Lambeau, G., Gelb, M., Kelvin, D. J., & Rubin, B. B. (2014). Lack of group X secreted phospholipase A₂ increases survival following pandemic H1N1 influenza infection. Virology, 454-455(1), 78-92. https://doi.org/10.1016/j.virol.2014.01.030

Kelvin, AA, Degousee, N, Banner, D, Stefanski, E, León, AJ, Angoulvant, D, Paquette, SG, Huang, SSH, Danesh, A, Robbins, CS, Noyan, H, Husain, M, Lambeau, G, Gelb, M, Kelvin, DJ & Rubin, BB 2014, 'Lack of group X secreted phospholipase A₂ increases survival following pandemic H1N1 influenza infection', Virology, vol. 454-455, no. 1, pp. 78-92. https://doi.org/10.1016/j.virol.2014.01.030

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title = "Lack of group X secreted phospholipase A2 increases survival following pandemic H1N1 influenza infection",

abstract = "The role of Group X secreted phospholipase A2 (GX-sPLA2) during influenza infection has not been previously investigated. We examined the role of GX-sPLA2 during H1N1 pandemic influenza infection in a GX-sPLA2 gene targeted mouse (GX-/-) model and found that survival after infection was significantly greater in GX-/- mice than in GX+/+ mice. Downstream products of GX-sPLA2 activity, PGD2, PGE2, LTB4, cysteinyl leukotrienes and Lipoxin A4 were significantly lower in GX-/- mice BAL fluid. Lung microarray analysis identified an earlier and more robust induction of T and B cell associated genes in GX-/- mice. Based on the central role of sPLA2 enzymes as key initiators of inflammatory processes, we propose that activation of GX-sPLA2 during H1N1pdm infection is an early step of pulmonary inflammation and its inhibition increases adaptive immunity and improves survival. Our findings suggest that GX-sPLA2 may be a potential therapeutic target during influenza.",

author = "Kelvin, {Alyson A.} and Norbert Degousee and David Banner and Eva Stefanski and Le{\'o}n, {Alberto J.} and Denis Angoulvant and Paquette, {St{\'e}phane G.} and Huang, {Stephen S.H.} and Ali Danesh and Robbins, {Clinton S.} and Hossein Noyan and Mansoor Husain and Gerard Lambeau and Michael Gelb and Kelvin, {David J.} and Rubin, {Barry B.}",

note = "Funding Information: A/Mexico/4108/2009 was obtained through the Influenza Reagent Resource, Influenza Division, WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza, Centers for Disease Control and Prevention, Atlanta, GA, USA. We thank the Li Ka-Shing Foundation of Canada, Immune Diagnostics & Research, Shantou University Medical College, NIH (Grant R37 HL36235 ), NIH 1U01AI11598-01 Subaward no. 0038591(123721-3) to the support of this study and the Canadian Institutes of Health Research (CIHR) (Grant MOP 126205 (Dr. Rubin)) for the support of this study. We thank the staff from the Animal Resource Center of University Health Network for their help with the animal experiments. ",

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AU - Kelvin, Alyson A.

AU - Degousee, Norbert

AU - Banner, David

AU - Stefanski, Eva

AU - León, Alberto J.

AU - Angoulvant, Denis

AU - Paquette, Stéphane G.

AU - Huang, Stephen S.H.

AU - Danesh, Ali

AU - Robbins, Clinton S.

AU - Noyan, Hossein

AU - Husain, Mansoor

AU - Lambeau, Gerard

AU - Gelb, Michael

AU - Kelvin, David J.

AU - Rubin, Barry B.

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PY - 2014/4

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N2 - The role of Group X secreted phospholipase A2 (GX-sPLA2) during influenza infection has not been previously investigated. We examined the role of GX-sPLA2 during H1N1 pandemic influenza infection in a GX-sPLA2 gene targeted mouse (GX-/-) model and found that survival after infection was significantly greater in GX-/- mice than in GX+/+ mice. Downstream products of GX-sPLA2 activity, PGD2, PGE2, LTB4, cysteinyl leukotrienes and Lipoxin A4 were significantly lower in GX-/- mice BAL fluid. Lung microarray analysis identified an earlier and more robust induction of T and B cell associated genes in GX-/- mice. Based on the central role of sPLA2 enzymes as key initiators of inflammatory processes, we propose that activation of GX-sPLA2 during H1N1pdm infection is an early step of pulmonary inflammation and its inhibition increases adaptive immunity and improves survival. Our findings suggest that GX-sPLA2 may be a potential therapeutic target during influenza.

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