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Journal of Virology, August 2009, p. 7475-7486, Vol. 83, No. 15
0022-538X/09/$08.00+0 doi:10.1128/JVI.01434-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Association of Increased Pathogenicity of Asian H5N1 Highly Pathogenic Avian Influenza Viruses in Chickens with Highly Efficient Viral Replication Accompanied by Early Destruction of Innate Immune Responses
,
Koutaro Suzuki,1,5
Hironao Okada,4,5
Toshihiro Itoh,4,5
Tatsuya Tada,1,5
Masaji Mase,1
Kikuyasu Nakamura,2
Masanori Kubo,3 and
Kenji Tsukamoto1,5*
Research Team for Zoonotic Diseases,1 Research Team for Viral Disease,2 Research Team for Epidemiology, National Institute of Animal Health (NIAH), National Agriculture and Food Research Organization (NARO), 3-1-5 Kannondai, Tsukuba, Ibaraki 305-0856, Japan,3 National Institute of Advanced Industrial Science and Technology (AIST), 1-2-1 Namiki, Tsukuba, Ibaraki 305-8564, Japan,4 Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, 4-1-8 Honcho, Kawaguchi-shi, Saitama 332-0012, Japan5
Received 9 July 2008/ Accepted 9 May 2009
The Asian H5N1 highly pathogenic avian influenza (HPAI) viruses have been increasing in pathogenicity in diverse avian species since 1996 and are now widespread in Asian, European, and African countries. To better understand the basis of the increased pathogenicity of recent Asian H5N1 HPAI viruses in chickens, we compared the fevers and mean death times (MDTs) of chickens infected with the Asian H5N1 A/chicken/Yamaguchi/7/04 (CkYM7) strain with those infected with the H5N1 Duck/Yokohama/aq10/03 (DkYK10) strain, using a wireless thermosensor. Asian H5N1 CkYM7 caused peracute death in chickens before fever could be induced, whereas DkYK10 virus induced high fevers and had a long MDT. Real-time PCR analyses of cytokine mRNA expressions showed that CkYM7 quickly induced antiviral and proinflammatory cytokine mRNA expressions at 24 h postinfection (hpi) that suddenly decreased at 32 hpi. In contrast, these cytokine mRNA expressions increased at 24 hpi in the DkYK10 group, but decreased from 48 hpi onward to levels similar to those resulting from infection with the low-pathogenicity H5N2 A/chicken/Ibaraki/1/2004 strain. Sequential titrations of viruses in lungs, spleens, and kidneys demonstrated that CkYM7 replicated rapidly and efficiently in infected chickens and that the viral titers were more than twofold higher than those of DkYK10. CkYM7 preferentially and efficiently replicated in macrophages and vascular endothelial cells, while DkYK10 grew moderately in macrophages. These results indicate that the increased pathogenicity in chickens of the recent Asian H5N1 HPAI viruses may be associated with extremely rapid and high replication of the virus in macrophages and vascular endothelial cells, which resulted in disruption of the thermoregulation system and innate immune responses.
* Corresponding author. Mailing address: Research Team for Zoonotic Diseases, National Institute of Animal Health, 3-1-5 Kannondai, Tsukuba, Ibaraki 305-0856, Japan. Phone and fax: 81-29-838-7760. E-mail: ktsukamo{at}affrc.go.jp
Published ahead of print on 20 May 2009.
Supplemental material for this article may be found at http://jvi.asm.org/.
Journal of Virology, August 2009, p. 7475-7486, Vol. 83, No. 15
0022-538X/09/$08.00+0 doi:10.1128/JVI.01434-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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