Interaction ofinfluenza virus hemagglutinin withtarget membrane lipids isakeystepinvirus-induced hemolysis andfusion atpH5.2

摘要: Themolecular mechanism ofhemolysis andfu- sion byinfluenza virus inacidic media wasstudied. First, theeffect oftrypsin treatment ontheactivity offibroblast-grown influenza Theresults showed that thesplit form ofviral hemagglutinin, HA1andHA2, butnottheprecursor, isresponsible fortheactivity. Second, theinteraction ofegg-grown virus, which contains with lipid liposomes wasstudied byspin labeling andelectron microscopy. Phospho- transfer fromtheviral envelope tothelipid bilayer mem- brane occurred within 30satpH4.5-5.4. Thetransfer islargely independent ofthelipid composition andthecrystalline vs.liquid/ crystalline state ofthemembrane. Virus-induced lysis ofliposomes also took place rapidly inthesamepHrange. Envelope fusion atpH5.2butnotatpH7.0. These charac- teristic interactions weresimilar tothose between anderythrocytes reported previously. Ontheother hand, hem- agglutinating ofJapan did notinteract atneu- tral pH.These results suggest protonation oftheNH2-ter- minal segment oftheHA2form causes interaction ofthesegment thelipid core ofthetarget cell membrane, leading tohemoly- sis andfusion. Werecently found shows amarkedly high enhancement andfusion ofhumanerythrocytes in acidic (pH5.0-5.4) (1). This isclosely related totheob- servation inacid (pH'6.0) bytoga- viruses such asSemliki forest, Sindbis, andrubella (2, 3). Fusion ofSemliki forest hasalso been observed (4, 5). observations haveopened upanewas- pect intheinfection ofthese (1, 4,5). Virus particles areadsorbed onto thetarget membrane andphag- ocytized viaviropexis. Theparticles thenreach intracellular secondary lysosomes, andthelowpHinside theorganella trig- gers oftheviral thelysosomal membranes. Theviral materials arethus transferred into cytoplasm. On theother hemagglutinating (HVJ, asyn- onymforSendai virus) hemolysis atneutral pH.This cantherefore its genetic material by target plasma Thepresent study wasundertaken toobtain further details onthemolecular oftheacid-induced and virus. involvement agglutinin glycoprotein wan% studied byusing grown chicken embryo fibroblasts. Ithasbeenshown thevirus hasaprecursor formofhemagglutinin (HAO) andthat trypsin splits theprecursor twofragments, HA1and HA2,toactivate infectivity 10-fold (6,7).Ininfluenza ineggs, apost translational modification hasbeenper- formed byprotease inhost cells orchorioallantoic fluid. We therefore thehemolysis activities ofinfluenza containing orthesplit ofhemagglu- tinin. hemagglutinin liposomes. ofhemagglutinin for lipids arethe probable site forthesplit hemagglutinin-induced