G45R on nonstructural protein 1 of influenza A virus contributes to virulence by increasing the expression of proinflammatory cytokines in mice

G45R on nonstructural protein 1 of influenza A virus contributes to virulence by increasing the... Nonstructural protein 1 (NS1) is a multifunctional protein that is a viral replication enhancer and virulence factor. In this study, we investigated the effect of the amino acid substitution G45R on the NS1 of A/Puerto Rico/8/1934 (H1N1) (G45R/NS1) on viral virulence and host gene expression in a mouse model and the human lung cell line A549. The G45R/NS1 virus had increased virulence by inducing an earlier and robust proinflammatory cytokine response in mice. Mice infected with the G45R/NS1 virus lost more body weight and had lower survival rates than mice infected with the wild type (WT/NS1) virus. Replication of the G45R/NS1 virus was higher than that of the WT/NS1 virus in vitro, but the replication of both viruses was similar in mouse lungs. In A549 cells, the majority of G45R/NS1 protein was localized in the cytoplasm whereas the majority of WT/NS1 protein was localized in the nucleus. Microarray analysis revealed that A549 cells infected with the G45R/NS1 virus had higher expression of genes encoding proteins associated with the innate immune response and cytokine activity than cells infected with the WT/NS1 virus. These data agree with cytokine production observed in mouse lungs. Our findings suggest that G45R on NS1 protein contributes to viral virulence by increasing the expression of inflammatory cytokines early in infection. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Virology Springer Journals

G45R on nonstructural protein 1 of influenza A virus contributes to virulence by increasing the expression of proinflammatory cytokines in mice

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Publisher
Springer Vienna
Copyright
Copyright © 2016 by Springer-Verlag Wien
Subject
Biomedicine; Virology; Medical Microbiology; Infectious Diseases
ISSN
0304-8608
eISSN
1432-8798
D.O.I.
10.1007/s00705-016-3072-8
Publisher site
See Article on Publisher Site

Abstract

Nonstructural protein 1 (NS1) is a multifunctional protein that is a viral replication enhancer and virulence factor. In this study, we investigated the effect of the amino acid substitution G45R on the NS1 of A/Puerto Rico/8/1934 (H1N1) (G45R/NS1) on viral virulence and host gene expression in a mouse model and the human lung cell line A549. The G45R/NS1 virus had increased virulence by inducing an earlier and robust proinflammatory cytokine response in mice. Mice infected with the G45R/NS1 virus lost more body weight and had lower survival rates than mice infected with the wild type (WT/NS1) virus. Replication of the G45R/NS1 virus was higher than that of the WT/NS1 virus in vitro, but the replication of both viruses was similar in mouse lungs. In A549 cells, the majority of G45R/NS1 protein was localized in the cytoplasm whereas the majority of WT/NS1 protein was localized in the nucleus. Microarray analysis revealed that A549 cells infected with the G45R/NS1 virus had higher expression of genes encoding proteins associated with the innate immune response and cytokine activity than cells infected with the WT/NS1 virus. These data agree with cytokine production observed in mouse lungs. Our findings suggest that G45R on NS1 protein contributes to viral virulence by increasing the expression of inflammatory cytokines early in infection.

Journal

Archives of VirologySpringer Journals

Published: Sep 23, 2016

References

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