[The change in functional activity and primary structure of the M2 protein in variants of the influenza virus resistant to remantadine and deitiforin: common and individual differences from the original strain].
The two variants of influenza A/Victoria/35/72 (H3N2) virus resistant simultaneously to remantadine, deitiforin, adapromine and amantadine were obtained while passaging the virus in presence of remantadine or deitiforin. Both variants differed from the parental strain in optimal pH for hemolysis, transcriptase activity and in amino acid sequence of M2 protein. Maximal hemolytic activity of the parental strain is registered at pH 5.2, for the variants cultured in the presence of remantadine or deitiforin at pH 5.5 and 5.8, respectively. In contrast to NH4OH, remantadine and deitiforin do not exert inhibition of virus-induced hemolysis. Transcriptase activity of resistant variants is about 50% higher as compared with parental strain (enzyme source--whole virus particles or RNP). The M2 protein of the remantadine variant has 2 amino acid substitutions: 31 (Ser----Asn) and 59 (Met----Leu); the deitiforin variant has 3 substitutions: 14 (Met----Leu), 30 (Ala----Val) and 59 (Met----Leu). The phenotypic resistance of the virus seems to be determined by the mutations in the hydrophobic protein region (30,31); the other substitutions (14,59) may modify conformational structure and functional activity of the viral proteins.
Kozeletskaia
K N
KN
Blinov
V M
VM
Karginov
V A
VA
Burmistrova
V V
VV
Siniakov
A N
AN
Golubev
D B
DB
D000218:Adamantane; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000494:pharmacology*; D001483:Base Sequence; D004352:Drug Resistance, Microbial; D005814:Genes, Viral; D009980:Influenza A virus / Q000187:drug effects* / Q000235:genetics; D008969:Molecular Sequence Data; D009930:Organic Chemicals; D011487:Protein Conformation; D012299:Rimantadine / Q000494:pharmacology*; D014763:Viral Matrix Proteins / Q000235:genetics*; D000086082:Viroporin Proteins
D000218:Adamantane; D000998:Antiviral Agents; D009930:Organic Chemicals; D012299:Rimantadine; D014763:Viral Matrix Proteins; C031540:M-protein, influenza virus; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins; C060204:deitiforin
Izmenenie funktsional'noĭ aktivnosti i pervichnoĭ struktury belka M2 u rezistentnykh k remantadinu i deĭtiforinu variantov virusa grippa: obschie i individual'nye otlichiia ot iskhodnogo shtamma.