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Journal of Virology, May 2009, p. 4704-4708, Vol. 83, No. 9
0022-538X/09/$08.00+0     doi:10.1128/JVI.01987-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Neuraminidase Stalk Length and Additional Glycosylation of the Hemagglutinin Influence the Virulence of Influenza H5N1 Viruses for Mice{triangledown}

Yumiko Matsuoka,1,§ David E. Swayne,2 Colleen Thomas,2 Marie-Anne Rameix-Welti,3 Nadia Naffakh,3 Christine Warnes,1 Melanie Altholtz,1,{dagger} Ruben Donis,1 and Kanta Subbarao1,§*

Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia,1 Southeast Poultry Research Laboratory, Agricultural Research Service, United States Department of Agriculture, Athens, Georgia,2 Institut Pasteur, Unité de Génétique Moléculaire des Virus à ARN, URA CNRS 3015, Paris, France3

Received 19 September 2008/ Accepted 3 February 2009

Following circulation of avian influenza H5 and H7 viruses in poultry, the hemagglutinin (HA) can acquire additional glycosylation sites, and the neuraminidase (NA) stalk becomes shorter. We investigated whether these features play a role in the pathogenesis of infection in mammalian hosts. From 1996 to 2007, H5N1 viruses with a short NA stalk have become widespread in several avian species. Compared to viruses with a long-stalk NA, viruses with a short-stalk NA showed a decreased capacity to elute from red blood cells and an increased virulence in mice, but not in chickens. The presence of additional HA glycosylation sites had less of an effect on virulence than did NA stalk length. The short-stalk NA of H5N1 viruses circulating in Asia may contribute to virulence in humans.

* Corresponding author. Present address: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 33 North Drive, MSC 3203, Bethesda, MD 20892. Phone: (301) 451-3839. Fax: (301) 480-5719. E-mail: ksubbarao{at}niaid.nih.gov

{triangledown} Published ahead of print on 18 February 2009.

§ Present address: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 33 North Drive, MSC 3203, Bethesda, MD 20892.

{dagger} Present address: Department of Obstetrics and Gynecology, Tufts Medical Center, 800 Washington Street #22, Boston, MA 02111.

Journal of Virology, May 2009, p. 4704-4708, Vol. 83, No. 9
0022-538X/09/$08.00+0     doi:10.1128/JVI.01987-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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