Highly Pathogenic AI H5N1 Viruses Elicit an Attenuated Type I Interferon Response in

sharon sanders · Oct 26, 2007

Highly Pathogenic Avian Influenza H5N1 Viruses Elicit an Attenuated Type I Interferon Response in Polarized Human Bronchial Epithelial Cells
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Hui Zeng,1 Cynthia Goldsmith,2 Pranee Thawatsupha,3 Malinee Chittaganpitch,3 Sunthareeya Waicharoen,3 Sherif Zaki,2 Terrence M. Tumpey,1 and Jacqueline M. Katz1*

Immunology and Pathogenesis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases,1 Infectious Disease Pathology Branch, Division of Viral and Rickettsial Diseases, National Center for Zoonotic, Vector-Borne, and Enteric Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333,2 Thai National Influenza Center, National Institute of Health, Ministry of Public Health, Bangkok 11000, Thailand3
Received 24 May 2007/ Accepted 29 August 2007
The unparalleled spread of highly pathogenic avian influenza A (HPAI) H5N1 viruses has resulted in devastating outbreaks in domestic poultry and sporadic human infections with a high fatality rate. To better understand the mechanism(s) of H5N1 virus pathogenesis and host responses in humans, we utilized a polarized human bronchial epithelial cell model that expresses both avian alpha-2,3- and human alpha-2,6-linked sialic acid receptors on the apical surface and supports productive replication of both H5N1 and H3N2 viruses. Using this model, we compared the abilities of selected 2004 HPAI H5N1 viruses isolated from humans and a recent human H3N2 virus to trigger the type I interferon (IFN) response. H5N1 viruses elicited significantly less IFN regulatory factor 3 (IRF3) nuclear translocation, as well as delayed and reduced production of IFN-? compared with the H3N2 virus. Furthermore, phosphorylation of Stat2 and induction of IFN-stimulated genes (ISGs), such as MX1, ISG15, IRF7, and retinoic acid-inducible gene I, were substantially delayed and reduced in cells infected with H5N1 viruses. We also observed that the highly virulent H5N1 virus replicated more efficiently and induced a weaker IFN response than the H5N1 virus that exhibited low virulence in mammals in an earlier study. Our data suggest that the H5N1 viruses tested, especially the virus with the high-pathogenicity phenotype, possess greater capability to attenuate the type I IFN response than the human H3N2 virus. The attenuation of this critical host innate immune defense may contribute to the virulence of H5N1 viruses observed in humans. 
<HR align=left width="50%">* Corresponding author. Mailing address: Centers for Disease Control and Prevention, 1600 Clifton Road, MS G16, Atlanta, GA 30333. Phone: <?XML:NAMESPACE PREFIX = SKYPE /><SKYPE:SPAN onmouseup="javascript:skype_tb_imgOnOff(this,1,'0',true,16,'');return skype_tb_stopEvents();" class=skype_tb_injection oncontextmenu="javascript:skype_tb_SwitchDrop(this,'0','sms=0');return skype_tb_stopEvents();" onmousedown="javascript:skype_tb_imgOnOff(this,2,'0',true,16,'');return skype_tb_stopEvents();" id=softomate_highlight_0 onmouseover="javascript:skype_tb_imgOnOff(this,1,'0',true,16,'');" title="Call this phone number in United States of America with Skype: +14046394966" onclick="javascript:doRunCMD('call','0',null,0);return skype_tb_stopEvents();" onmouseout="javascript:skype_tb_imgOnOff(this,0,'0',true,16,'');" IamRTL="0" context="(404) 639-4966" durex="0"><SKYPE:SPAN onmouseup="javascript:doSkypeFlag(this,'0',1,1,16);return skype_tb_stopEvents();" class=skype_tb_imgA onmousedown="javascript:doSkypeFlag(this,'0',2,1,16);return skype_tb_stopEvents();" id=skype_tb_droppart_0 onmouseover="javascript:doSkypeFlag(this,'0',1,1,16);" title="Change country code ..." style="BACKGROUND-IMAGE: url(C:\Users\Sharon\AppData\Local\Temp\Low\__SkypeIEToolbar_Cache\e70d95847a8f5723cfca6b3fd9946506\static\inactive_a.compat.flex.w16.gif)" onclick="javascript:doHandleChdial(this,1,'0',1);return skype_tb_stopEvents();" onmouseout="javascript:doSkypeFlag(this,'0',0,1,16);"><SKYPE:SPAN class=skype_tb_imgFlag id=skype_tb_img_f0 style="BACKGROUND-IMAGE: url(C:\Users\Sharon\AppData\Local\Temp\Low\__SkypeIEToolbar_Cache\e70d95847a8f5723cfca6b3fd9946506\static\famfamfam/US.gif)"></SKYPE:SPAN></SKYPE:SPAN><SKYPE:SPAN class=skype_tb_imgS id=skype_tb_img_s0></SKYPE:SPAN><SKYPE:SPAN class=skype_tb_injectionIn id=skype_tb_text0><SKYPE:SPAN class=skype_tb_innerText id=skype_tb_innerText0>(404) 639-4966</SKYPE:SPAN></SKYPE:SPAN><SKYPE:SPAN class=skype_tb_imgR id=skype_tb_img_r0></SKYPE:SPAN></SKYPE:SPAN>. Fax: (404) 639-2350. E-mail: jmk9@cdc.gov<SCRIPT type=text/javascript></SCRIPT>

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Published ahead of print on 12 September 2007. 

http://jvi.asm.org/cgi/content/abstract/81/22/12439

Highly Pathogenic AI H5N1 Viruses Elicit an Attenuated Type I Interferon Response in

sharon sanders

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