Persistent influenza C virus possesses distinct functional properties due to a modified HEF glycoprotein.
A model of long term viral persistence has been established by selecting a spontaneous mutant strain of influenza C/Ann Arbor/1/50 virus in a permanent carrier culture of MDCK cells. Infectivity and cell tropism are mainly determined by the multifunctional viral membrane glycoprotein (HEF). HEF analysis was aimed at identifying a putative correlation between sequence and function, i.e. receptor binding, enzymatic activity, antigenicity and rate of infection. The current experimental picture is summarized by the following findings: (i) C/Ann Arbor/1/50 persistent virus carries a modified receptor-binding sequence, (ii) receptor-binding activity is altered, as indicated by a higher efficiency in recognizing low amounts of the receptor determinant N-acetyl-9-O-acetylneuraminic acid, (iii) direct attachment to cell surfaces differs from that of wild-type virus, as measured by slower kinetics of viral elution, (iv) receptor-destroying enzymatic activity is diminished, (v) characteristic features of virion surface morphology are altered or unstable, (vi) persistent-type HEF epitopes are distinguishable by monoclonal antibodies from wild-type and (vii) viral infectivity is intensified for cells bearing a low number of receptors. The sum of these changes highlights a structurally and functionally modified HEF glycoprotein that allows long term viral persistence. In order to clarify which of the described points are required for the persistent viral phenotype, a working concept is presented.
Marschall
M
M
Abteilung für Virologie, Technische Universität München, Germany.
Herrler
G
G
Böswald
C
C
Foerst
G
G
Meier-Ewert
H
H
D000818:Animals; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D002460:Cell Line; D002642:Chick Embryo; D002645:Chickens; D017931:DNA Primers; D004285:Dogs; D000939:Epitopes / Q000032:analysis; D004912:Erythrocytes / Q000502:physiology; D005347:Fibroblasts / Q000382:microbiology; D014644:Genetic Variation; D006386:Hemagglutination Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000235:genetics* / Q000378:metabolism*; D009982:Gammainfluenzavirus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D007668:Kidney; D007700:Kinetics; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods; D011991:Receptors, Virus / Q000502:physiology*; D014771:Virion / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology
D000911:Antibodies, Monoclonal; D017931:DNA Primers; D000939:Epitopes; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D011991:Receptors, Virus