A monoclonal antibody specific to the HA2 glycoprotein of influenza A virus hemagglutinin that inhibits its fusion activity reduces replication of the virus.
Monoclonal antibody (MAb) CF2, which binds to the fusion peptide of influenza A virus hemagglutinin (HA) (amino acids (aa) 1-35 of the N-terminus of the light chain of HA), inhibited the fusion activity of HA. This MAb preferentially bound to pH 5-treated virus (with conformationally altered HA) and bound only weakly to the native wild type (wt) virus. However, a significant binding of MAb CF2 to the amantadine resistant virus mutant Ab4 (with a mutation at aa 17 of HA1 leading to a destabilization of HA trimer) was obtained without pH 5 treatment. Exploiting the fusion-inhibition activity of MAb CF2 the effect of this antibody on the virus replication in vitro was followed using both the wt virus and the amantadine resistant mutant Ab4. No reduction of replication of wt virus and a low reduction of replication of Ab4 mutant (by about 20%) was detected by radioimmunoassay after preincubation of the virus with a high concentration of MAb CF2 at room temperature. An increased reduction of replication of Ab4 mutant (by about 40%) was observed in cell radioimmunoassay (RIA) and in plaque assay when the virus was preincubated with MAb at 37 degrees C. Under these conditions a reduction of the wt virus replication also occurred by about 40%. This is the first report on the capacity of a MAb specific to HA2 gp, the light chain of influenza A virus HA, to reduce replication of the virus. This capacity in relation to (i) the affinity of the antibody to the virus, and (ii) the accessibility of corresponding epitopes on the virus surface as well as the proposed mechanism of inhibition of replication of the virus are discussed.
Varecková
E
E
Institute of Virology, Slovak Academy of Sciences, Dúbravská cesta 9, 845 05 Bratislava 4, Slovak Republic. viruevar@savba.sk
Wharton
S A
SA
Mucha
V
V
Gocník
M
M
Kostolanský
F
F
D000547:Amantadine / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000914:Antibodies, Viral / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology; D024882:Drug Resistance, Viral / Q000235:genetics; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000276:immunology*; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D008561:Membrane Fusion; D051379:Mice; D009154:Mutation; D011487:Protein Conformation; D014760:Viral Fusion Proteins / Q000737:chemistry / Q000276:immunology; D010948:Viral Plaque Assay; D014779:Virus Replication
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000998:Antiviral Agents; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D014760:Viral Fusion Proteins; D000547:Amantadine