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Journal of Virology, June 2009, p. 5825-5834, Vol. 83, No. 11
0022-538X/09/$08.00+0 doi:10.1128/JVI.02144-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Early Control of H5N1 Influenza Virus Replication by the Type I Interferon Response in Mice
Kristy J. Szretter,1,2,
Shivaprakash Gangappa,1
Jessica A. Belser,1
Hui Zeng,1
Hualan Chen,1,
Yumiko Matsuoka,1,
Suryaprakash Sambhara,1
David E. Swayne,3
Terrence M. Tumpey,1 and
Jacqueline M. Katz1*
Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333,1 Emory University, Atlanta, Georgia 30322,2 Southeast Poultry Research Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Athens, Georgia 306063
Received 10 October 2008/ Accepted 27 February 2009
Widespread distribution of highly pathogenic avian H5N1 influenza viruses in domesticated and wild birds continues to pose a threat to public health, as interspecies transmission of virus has resulted in increasing numbers of human disease cases. Although the pathogenic mechanism(s) of H5N1 influenza viruses has not been fully elucidated, it has been suggested that the ability to evade host innate responses, such as the type I interferon response, may contribute to the virulence of these viruses in mammals. We investigated the role that type I interferons (alpha/beta interferon [IFN-
/β]) might play in H5N1 pathogenicity in vivo, by comparing the kinetics and outcomes of H5N1 virus infection in IFN-/β receptor (IFN-/βR)-deficient and SvEv129 wild-type mice using two avian influenza A viruses isolated from humans, A/Hong Kong/483/97 (HK/483) and A/Hong Kong/486/97 (HK/486), which exhibit high and low lethality in mice, respectively. IFN-/βR-deficient mice experienced significantly more weight loss and more rapid time to death than did wild-type mice. HK/486 virus caused a systemic infection similar to that with HK/483 virus in IFN-/βR-deficient mice, suggesting a role for IFN-/β in controlling the systemic spread of this H5N1 virus. HK/483 virus replicated more efficiently than HK/486 virus both in vivo and in vitro. However, replication of both viruses was significantly reduced following pretreatment with IFN-/β. These results suggest a role for the IFN-/β response in the control of H5N1 virus replication both in vivo and in vitro, and as such it may provide some degree of protection to the host in the early stages of infection.
* Corresponding author. Mailing address: Influenza Division MS G-16, 1600 Clifton Rd., NE, Atlanta, GA 30333. Phone: (404) 639-4966. Fax: (404) 639-2334. E-mail: JKatz{at}cdc.gov
Published ahead of print on 18 March 2009.
Present address: Washington University, School of Medicine, Saint Louis, MO 63110.
Present address: Harbin Veterinary Research Institute, 427 Maduan Street, Harbin 150001, People's Republic of China.
Present address: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, 33 North Drive, MSC 3203, Bethesda, MD 20892.
Journal of Virology, June 2009, p. 5825-5834, Vol. 83, No. 11
0022-538X/09/$08.00+0 doi:10.1128/JVI.02144-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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