Human influenza viruses derive their genes from avian viruses. The neuraminidase (NA) of the avian viruses has, in addition to the catalytic site, a separate sialic acid binding site (hemadsorption site) that is not present in human viruses. The biological significance of the NA hemadsorption activity in avian influenza viruses remained elusive. A sequence database analysis revealed that the NAs of the majority of human H2N2 viruses isolated during the influenza pandemic of 1957 differ from their putative avian precursor by amino acid substitutions in the hemadsorption site. We found that the NA of a representative pandemic virus A/Singapore/1/57 (H2N2) lacks hemadsorption activity and that a single reversion to the avian-virus-like sequence (N367S) restores hemadsorption. Using this hemadsorption-positive NA, we generated three NA variants with substitutions S370L, N400S and W403R that have been found in the hemadsorption site of human H2N2 viruses. Each substitution abolished hemadsorption activity. Although, there was no correlation between hemadsorption activity of the NA variants and their enzymatic activity with respect to monovalent substrates, all four hemadsorption-negative NAs desialylated macromolecular substrates significantly slower than did the hemadsorption-positive counterpart. The NA of the 1918 pandemic virus A/Brevig Mission/1/18 (H1N1) also differed from avian N1 NAs by reduced hemadsorption activity and less efficient hydrolysis of macromolecular substrates. Our data indicate that the hemadsorption site serves to enhance the catalytic efficiency of NA and they suggest that, in addition to changes in the receptor-binding specificity of the hemagglutinin, alterations of the NA are needed for the emergence of pandemic influenza viruses.
机构:St Jude Childrens Res Hosp, Div Virol, Dept Infect Dis, 332 N Lauderdale St, Memphis, TN 38105 USA
Aamir, U. B.
Wernery, Ulrich
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机构:St Jude Childrens Res Hosp, Div Virol, Dept Infect Dis, 332 N Lauderdale St, Memphis, TN 38105 USA
Wernery, Ulrich
Ilyushina, N.
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机构:St Jude Childrens Res Hosp, Div Virol, Dept Infect Dis, 332 N Lauderdale St, Memphis, TN 38105 USA
Ilyushina, N.
Webster, R. G.
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St Jude Childrens Res Hosp, Div Virol, Dept Infect Dis, 332 N Lauderdale St, Memphis, TN 38105 USASt Jude Childrens Res Hosp, Div Virol, Dept Infect Dis, 332 N Lauderdale St, Memphis, TN 38105 USA
机构:
Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA
Emory Univ, Atlanta, GA 30322 USACtr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA
Belser, Jessica A.
Blixt, Ola
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Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA
Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USACtr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA
Blixt, Ola
Chen, Li-Mei
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Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USACtr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA
Chen, Li-Mei
Pappas, Claudia
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Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USACtr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA
Pappas, Claudia
Maines, Taronna R.
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Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USACtr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA
Maines, Taronna R.
Van Hoeven, Neal
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Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USACtr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA
Van Hoeven, Neal
Donis, Ruben
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Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USACtr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA
Donis, Ruben
Busch, Julia
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Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA
Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USACtr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA
Busch, Julia
McBride, Ryan
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Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA
Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USACtr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA
McBride, Ryan
Paulson, James C.
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Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA
Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USACtr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA
Paulson, James C.
Katz, Jacqueline M.
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Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USACtr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA
Katz, Jacqueline M.
Tumpey, Terrence M.
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Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USACtr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA
机构:
Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USAUniv Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA
Bousse, Tatiana
Takimoto, Toru
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机构:
Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USAUniv Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA
机构:St Jude Childrens Res Hosp, Div Virol, Dept Infect Dis, 332 N Lauderdale St, Memphis, TN 38105 USA
Aamir, U. B.
Wernery, Ulrich
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h-index: 0
机构:St Jude Childrens Res Hosp, Div Virol, Dept Infect Dis, 332 N Lauderdale St, Memphis, TN 38105 USA
Wernery, Ulrich
Ilyushina, N.
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h-index: 0
机构:St Jude Childrens Res Hosp, Div Virol, Dept Infect Dis, 332 N Lauderdale St, Memphis, TN 38105 USA
Ilyushina, N.
Webster, R. G.
论文数: 0引用数: 0
h-index: 0
机构:
St Jude Childrens Res Hosp, Div Virol, Dept Infect Dis, 332 N Lauderdale St, Memphis, TN 38105 USASt Jude Childrens Res Hosp, Div Virol, Dept Infect Dis, 332 N Lauderdale St, Memphis, TN 38105 USA
机构:
Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA
Emory Univ, Atlanta, GA 30322 USACtr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA
Belser, Jessica A.
Blixt, Ola
论文数: 0引用数: 0
h-index: 0
机构:
Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA
Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USACtr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA
Blixt, Ola
Chen, Li-Mei
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h-index: 0
机构:
Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USACtr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA
Chen, Li-Mei
Pappas, Claudia
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h-index: 0
机构:
Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USACtr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA
Pappas, Claudia
Maines, Taronna R.
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h-index: 0
机构:
Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USACtr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA
Maines, Taronna R.
Van Hoeven, Neal
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h-index: 0
机构:
Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USACtr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA
Van Hoeven, Neal
Donis, Ruben
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h-index: 0
机构:
Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USACtr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA
Donis, Ruben
Busch, Julia
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h-index: 0
机构:
Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA
Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USACtr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA
Busch, Julia
McBride, Ryan
论文数: 0引用数: 0
h-index: 0
机构:
Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA
Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USACtr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA
McBride, Ryan
Paulson, James C.
论文数: 0引用数: 0
h-index: 0
机构:
Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA
Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USACtr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA
Paulson, James C.
Katz, Jacqueline M.
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h-index: 0
机构:
Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USACtr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA
Katz, Jacqueline M.
Tumpey, Terrence M.
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h-index: 0
机构:
Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USACtr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA
机构:
Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USAUniv Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA
Bousse, Tatiana
Takimoto, Toru
论文数: 0引用数: 0
h-index: 0
机构:
Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USAUniv Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA