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Journal of Virology, September 1998, p. 7626-7631, Vol. 72, No. 9
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
The Role of Influenza A Virus Hemagglutinin Residues 226 and 228 in Receptor Specificity and Host Range Restriction
Angela
Vines,1,
Krisna
Wells,1,2
Mikhail
Matrosovich,1
Maria R.
Castrucci,3
Toshihiro
Ito,4 and
Yoshihiro
Kawaoka1,2,5,*
Department of Virology and Molecular Biology,
St. Jude Children's Research Hospital, Memphis, Tennessee
381051;
Department of Pathobiological
Sciences, School of Veterinary Medicine, University of
Wisconsin
Madison, Madison, Wisconsin
537062;
Department of Virology,
Instituto Superiore di Sanita, 00161 Rome,
Italy3;
Department of Veterinary
Public Health, Faculty of Agriculture, Tottori University, Tottori
680, Japan4; and
Department of
Pathology, University of Tennessee, Memphis, Memphis, Tennessee
381635
Received 13 March 1998/Accepted 19 May 1998
Influenza A viruses can be isolated from a variety of animals, but
their range of hosts is restricted. For example, human influenza viruses do not replicate in duck intestine, the major replication site of avian viruses in ducks. Although amino acids at
positions 226 and 228 of hemagglutinin (HA) of the H3 subtype are known
to be important for this host range restriction, the contributions of
specific amino acids at these positions to restriction were not known.
Here, we address this issue by generating HAs with site-specific
mutations of a human virus that contain different amino acid residues
at these positions. We also let ducks select replication-competent viruses from a
replication-incompetent virus containing a human virus HA by
inoculating animals with 1010.5 50% egg infectious dose of
the latter virus and identified a mutation in the HA. Our results
showed that the Ser-to-Gly mutation at position 228, in addition to the
Leu-to-Gln mutation at position 226 of the HA of the H3 subtype, is
critical for human virus HA to support virus replication in duck
intestine.
*
Corresponding author. Mailing address: Department of
Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin
Madison, 2015 Linden Dr. West, Madison, WI 53706. Phone: (608) 265-4925. Fax: (608) 265-5622. E-mail:
kawaokay{at}svm.vetmed.wisc.edu.

Present address: Department of Biology, Spelman College, Atlanta,
GA 30314-4399.
Journal of Virology, September 1998, p. 7626-7631, Vol. 72, No. 9
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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