The methyltransferase inhibitor Neplanocin A interferes with influenza virus replication by a mechanism different from that of 3-deazaadenosine.
Neplanocin A (NeplA) and 3-deazaadenosine (3DA-Ado) are both inhibitors of methyltransferases, and both interfere with influenza virus replication. Their modes of action, however, are different. In chicken embryo cells NeplA inhibits only in media depleted of or low in methionine, while 3DA-Ado acts independently of the concentration of methionine. While homocysteine partially reverses the effect of NeplA, it strongly potentiates the effect of 3DA-Ado. While NeplA inhibits the synthesis of all viral proteins to nearly the same extent, 3DA-Ado interferes only with the production of late proteins (Fischer et al. (1990) Virology 177, 523-531). In NeplA-pretreated cells there is an extreme accumulation of S-adenosylhomocysteine, independent of the concentration of methionine in the medium, although NeplA inhibits influenza virus replication only in methionine-depleted medium. Therefore an accumulation of this intermediate by NeplA cannot account for the inhibitory effect, as has been implicated in the inhibition of the replication of other viruses. Our results indicate that at least two different methyltransferases are involved in influenza virus replication.
Woyciniuk
P
P
Institut für Virologie, Justus-Liebig-Universität, Giessen, Germany.
Linder
M
M
Scholtissek
C
C
D000241:Adenosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D043383:Adenosylhomocysteinase; D000818:Animals; D002642:Chick Embryo; D004357:Drug Synergism; D006710:Homocysteine / Q000494:pharmacology; D006867:Hydrolases / Q000037:antagonists & inhibitors; D009980:Influenza A virus / Q000187:drug effects* / Q000502:physiology; D008715:Methionine / Q000378:metabolism; D008780:Methyltransferases / Q000037:antagonists & inhibitors*; D012315:RNA Caps / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D014372:Tubercidin / Q000494:pharmacology*; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects*
D012315:RNA Caps; D012367:RNA, Viral; D014764:Viral Proteins; C018258:3-deazaadenosine; D006710:Homocysteine; C031096:neplanocin A; D012435:S-Adenosylhomocysteine; D008715:Methionine; D008780:Methyltransferases; D006867:Hydrolases; D043383:Adenosylhomocysteinase; D000241:Adenosine; D014372:Tubercidin