Fate of influenza A virion proteins after entry into subcellular fractions of LLC cells and the effect of amantadine.
Influenza A virus entry into the host cell was studied by monitoring the fate of virion proteins in subcellular fractions of LLC-RMK2 cells under conditions of low multiplicity of infection in the absence of drugs. Adsorption but not entry could be demonstrated at 4 degrees. Restricted entry into a prelysosomal pool could be demonstrated at 20 degrees. At 37 degrees proteins entered the cell in the same relative distribution as present in virions arguing against the fusion hypothesis and for the endocytosis hypothesis. The hemagglutinin and matrix proteins were readily degraded intracellularly at 37 degrees, but the nucleoprotein was relatively resistant to degradation, also consistent with the latter hypothesis. Amantadine blocked neither entry into the host cell nor transfer between the prelysosomal and lysosomal compartments; however, it appeared to block exit from the prelysosomal and lysosomal pools. The addition of the drug reduced degradation of the matrix protein in these pools but not of the hemagglutinin, consistent with inhibition by amantadine of fusion of virion envelope and vesicle membrane.
Richman
D D
DD
Hostetler
K Y
KY
Yazaki
P J
PJ
Clark
S
S
D000327:Adsorption; D000547:Amantadine / Q000494:pharmacology*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004705:Endocytosis; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000378:metabolism; D009980:Influenza A virus / Q000187:drug effects / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D008861:Microsomes / Q000378:metabolism; D009439:Neuraminidase / Q000494:pharmacology; D009698:Nucleoproteins / Q000378:metabolism*; D013696:Temperature; D014763:Viral Matrix Proteins; D014764:Viral Proteins / Q000378:metabolism*
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D009698:Nucleoproteins; D014763:Viral Matrix Proteins; D014764:Viral Proteins; D000547:Amantadine; D009439:Neuraminidase