Infectivity studies of influenza virus hemagglutinin receptor binding site mutants in mice.
The replicative properties of influenza virus hemagglutinin (HA) mutants with altered receptor binding characteristics were analyzed following intranasal inoculation of mice. Among the mutants examined was a virus containing a Y98F substitution at a conserved position in the receptor binding site that leads to a 20-fold reduction in binding. This mutant can replicate as well as wild-type (WT) virus in MDCK cells and in embryonated chicken eggs but is highly attenuated in mice, exhibiting titers in lungs more than 1,000-fold lower than those of the WT. The capacity of the Y98F mutant to induce antibody responses and the structural locations of HA reversion mutations are examined.
Meisner
Jeffrey
J
Emory University School of Medicine, Atlanta, GA 30322, USA.
Szretter
Kristy J
KJ
Bradley
Konrad C
KC
Langley
William A
WA
Li
Zhu-Nan
ZN
Lee
Byeong-Jae
BJ
Thoennes
Sudha
S
Martin
Javier
J
Skehel
John J
JJ
Russell
Rupert J
RJ
Katz
Jacqueline M
JM
Steinhauer
David A
DA
D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001665:Binding Sites; D001835:Body Weight; D002460:Cell Line; D002642:Chick Embryo; D004285:Dogs; D006385:Hemagglutination Inhibition Tests; D006389:Hemagglutinins, Viral / Q000235:genetics* / Q000378:metabolism*; D009980:Influenza A virus / Q000235:genetics* / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D020125:Mutation, Missense; D009976:Orthomyxoviridae Infections / Q000517:prevention & control / Q000821:virology; D017434:Protein Structure, Tertiary; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism*; D014774:Virulence; D014779:Virus Replication / Q000502:physiology
D000914:Antibodies, Viral; D006389:Hemagglutinins, Viral; D014764:Viral Proteins; C458881:hemagglutinin fusogenic peptide, influenza virus