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Puc. |
10. C1py1(Typmrn |
opramrn.11u111 |
Bl lll. |
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I JIUJIH,IJJlblH 0HcJtoii: 2 |
- gp 120; |
3 ·- |
|
4- --- |
1 |
hJJl'TOftHOrO |
|
yr.1y(i.T[('fHJC ,!1..TTH |
(JCt\PIITopa; 5 --pl7; G -p24; |
7 -p6, p9; |
- HIJTCrpa3a; 9 - o6panrn.si -rpancKplrn· |
Ta3a; |
10- rc·uoMl·P1H PHK; |
11 - npo-r<:a3a; J2- JHnepa/IIiHhIC TCJJhIJ..i. |
|
CJilleCKllM» 3JICMeIIT3M CJIC/J.YCT OTHCCTII Jl,.nHHHl>IC ((OHUCBble |
nornop1,1 (LTR) 11 3 CT[)YKTypu1,1., |
l'CIIa, |
Kn.ru1py1011u1x 6cJ11rn |
BHYTPCIIHHX CT[)YKTYP |
(g-i.1g·), |
<l>C[)MCIJ'f'I,] J[Jl51 J)CfJ.IIHK3UllH |
(pol) II 6e.1KII 060J101 rn11 |
(cnv) |
O;urnKo B OTJIIl'mc oT ,i:pyrux |
peTp0BIIpycoB l'CHbl |
pol |
!I |
cnv |
HC |
11cpe1<phtnaIOTCfl, :l |
0TJ1.CJIC |
Hbl p5IJ1.0M ]l.pyrnx pery.1 snopHb[X reH0B. y]X no KpaH HCM Mepe 6. Ce,IJ.bMOH perymnoptt1,IfI re11 pacno.rI0)Ke11 nocJIe retta cnv H noJJoBHHa ero 1rnxo,JJ,HTC.H B coCTanc LTR Ha 3'-KoHuc. Op
ramrnaiu·rn reHoMa |
Blf4 cJJe;_i_y1ow.aH: 5' -- LTR - gag - |
pol uettTpaJrbHLiti |
pattoH - cnvncf -- 3'- LTR. B co |
nase B114-2 nbrnBJJeH JlOTIOJJHHTC.nLHb1i'1 reH X fGyader et aI., 1987]. LleHTpoM y11pas.r1eH1rn aKTJJBHOCTH re110B, c 1<0TopL1M B33HMOJ1.Cl"icTBy10T TpaHC3l<THBaTOphl If ;wyrne pcryJISITOphl, CJIY )l<aT LTR, co,11,cplliaI1lHe pcrym1ropHb1e nocJ1e,JJ,0BaTeJib Hocrn.
KoHccpsaTnu111,1i\ JyKap11on1lfCCK11ii .9,:1cMCHT npo1vwropa TATAA pacno.,1araercn Me:>K,'W -27-M 11 -23-M 11y1<JJCOTH,D.a
MH LTR yCIJJJHTeJlh-MC}l(,l1,Y -109-M 11 -79-M HYKJ1eorn]la-
MII |
[fiyKpIIHCKIHI A. r., ByKpIIHCKIIH M. H., 1987; Siekevitz M. |
et |
a I., 1987J. |
yCIIJIHTeJib l"IMCCT r0M0JI0I'lI'IHbIC TI0CJie/1,0Ba |
TCJlLHUCTII c ycHJIHTCJJHMII ,Upyrnx m1pycon, uanpHMep OB40, IUIT0MeraJI0BHpyca, a TaK)KC C KJJCT01111LIMH ycIIJIHTCJl5IMII NF-xB H peryJrnrnp1mii 06m1cT1,10 re11a HITTepcfiepmrn. Ycn JIHTeJib C0,LI,CJ))KHT caiiT CBH3b!B3IIHH NF-xB fLu Y. ei al., 1989]. 1 IeranIBHbiil perymITopm,111 3.lteMCHT NRE, KOTOpbIH YMCHbWaeT CK0j)0CTb 3KCnpecc1rn reH0B, 113X0JJ,l!TC51 MClli/1,Y -420-M H 156-M 11yKJ1eoni;(aMH. B 31'011 o6mJCTII IUIX0JU!T
CH MHoro•rncJICHHbIC caiiTbl CBH3b!B3HHH I{JICT01 lllblX <[JaKTOpO!, |
TpaHCKpl!Illl,HH, K0T0pblC MoryT Cl!H3HTb CK0p0CTb 3Kcnpeccm, |
reHon [Lu Y. et al., 1989]. O6JtaCTb TAR, c KOTopofi B3aHM0· |
,UCHCTnyeT TpancKBJrnH33Top Tat, |
uaxo,1u1TcH MC2KJW |
4-M |
H +44-M HYKJIC0TH,UaMH. |
|
|
feHLI gag H pol C'Il!TL!BaI0TCH |
B pa Hll,IX paMKax |
33 C!JC1 |
pH60COMaJibl!Oro C}l,BHra paM h!I Ha 0,LI.IIH 1-1y1<JIC0TH,L(, 3'·K0HCU re1rn gag H 51 -Ko1-1eu rena pol nepeKpbmaIOTCH Ha 204240 ny1rneoTH}l,0B (B 3aBIICIIM0CTII OT oco6em1ocTCH II30JJ5ITa). fpynna HCCTpyKrypHIJ!X I'CII0B K0/1,IIJ)YCT Tpa11caKTHBaTo p1,1 - perymnopHLie 6eJIKII, 06,na,Ua1ouure ym1KcUib110ii cnoco6• H0CTbIO aKTHBnpoBan, <pyHKILIIll CT!JYKTYPHbIX H HCCTPYKTYP· Hb!X reifOB, PeryJIHTOJJIH,IC fCHbl npe,UcTaBJJHIOT co6oil HOBblti KJJaCC 5IB.11e1rnt'l B nnpycoJionrn, CBii}l,eTeJibCTBYIOIILHX 06 H30UL· petttt0CTH an11apwra reHeTw1eeKoro napasnTHsMa BHpycoB. C 3KcnpeccHeH 3THX reH0B, no-BH,UHMoMy, B 311a,rnTe.r1LHOii CTe nenu CBH3aH1,1 3Kc11pecc1u1 npomrpyca II 11cpexo,U H3 cTaJ1,1rn peerpHKUHH npom1pyca B CT3/l,HI0 3KTIIB3l IUI. B CBOI0 01Iepe11.1, OT liX 3KTHBII0CTII ll 133aHMOJ].ei!CTBIIH ,npyr C JLpyroM (HaIIpH Mep, rcnoB tat, rev II nef) 33BHCHT qiopMa Hil(j)CKIJ)!OHIIOl'O npouecca - 6yAYT Jrn .9T0 B3J)hIB penmma1LHH m1pyca H 6yp Hoe pa3BHTHC H!l(f)CKILHH mr6o )Ke penJIIIKaIJ,H5I 6yJJ,eT yMepcH HOH H opraHII3M cTaHeT 13 KaKofr-To CTerrem1 ce K0HTp0JIH
poBaTb.
5InJrem,e Tpa11caKTimaI1,HH 6bIJIO BnepBI,IC 0lIHC3H0 J].JIH pCTponnpyc:on 11eJ10BeKa HTLV-1 H HTLV-2, Ho pcryJrnTOpHbIC MCX3HH3Mbl y 3THX mrpycoB 0Ka3aJIHCb 3H3llllTCJibH0 npom.e H MeIICe aJ<TllBHbL
OcHOBHbIM MCT0J],0M 113yqemrn reH0B TpancaKTHBaT0[)0B 5IBH.IIHCb HanpaBJICHHbIC MYTail,lfll B o6JiaCTH 3THX I'CH0B H Il3Y· 1ICHHC nx BJJHHHIUI 11a penmrnaumo BHpyc:a, BBC,1],CHHe reH0B 3KTHBH0 pCIIllHUHJ)YlOlllJIXC5I LIIT3MM013B fCHCTIPICCKHl1 
aJI Jia6opaTOpHblX WTaMM0B, BJJHHHHC TJ)3HC3KTHBaT<Jpon Ha 3Kenpeccmo 6aKTepuaJibllbIX reHoB (reu x.nopaM<j)e1111KoJJ-aII,e THJITpaaccpepas1,1, CAT), 11axo,ll,H11J,HXC5I noJI Ko1npoJ1CM B11pyc Horo npoM0T0pa, If T. }],. BJ:19 C0/1,CJ))!{IIT no Kpai\Heit Mepe
6 perymnopHb!X reHOl3, 113 HHX 4 C H3BCCTHblM MexaHH3MOM
(HpOnJI<nI<3aJHJa(or H5IJIaJHH6JInJ.PHJAHaAyaJHH6JXH.BJ.A6e0arev
(o-r anrn. Hp,K1HJAHaA(pXBHpJJ.A6aof P.HKJaBHAJp.6JoMaP.)a
(or H5IIHCavirion infectivity factor) H nef (or aHrJI. negative
Hp,K1HJAHXayHbJAHoCarenaMH lannpnbH.JrrJJnKnIeCX1nYlanI<4Jpana51B
.1rn1orrn vpr H PBKa[Xa3eJ1Tai111 rOCA., BoHY-CraaJib ¢., MI11CHC a y B114-2 - vpx.
HaH6()JlCC aI<rl!BHl.,IM pcry.,rnTOpHl>IM reHOM 5IBJJ5ICTC5I reH |
tat, BKJIIOtJCHHC HJ1MBAHAaMO)KCT yc11JIIITI., B pCCCapa3 perrm1- |
I<anmo BHpyca. Ero rrpo,a,yrn COJlqrnrnr MepaM11HOI<HCJ10T c 06- |
JHtCTbIO OCTaTI<OB OCHODl!hlX |
H3Icccei3aelp,lT1a(2 J1113 H 6 Apr) |
H o6Jl8CThlO, o6oraJlll'IIIIOi'I |
1Teer1yeBreiIcaI<OTOpa5I |
o6ycJIOBJIH- |
83CT 06pa3013a1rnc JUIMcpon 6cJ1I<a <3HJ61v1act al., |
MI1KraC |
Ecn, ,l.l..'lHHbie () TOM, H11'0 <jly1mwrn rc11a tat 00/Iee MIIOl'006pa3JH1. IIanp1rnep, noK,rnano, tJro OJI perym1pyeT .:>I<cnpeccmo He TOJlbKO BHpycHb!X, HO II I<JICTO'il-IblX reHOB. C0CHOaBBe,IJ,CHHH rerrn JHJarro,U KOfITJ)OJlCM I3)a rpaHcreHHbIM MbilllaM noHB.1rn m1c1, nonpe)l<)].emrn K0)l{H, HanoM1rna10m1-1e lIapI<oMy Kan0311,
THKHM o6pa30M, reH M0)KCT Y'l3CTB0BaTb B CHMHT0M3THKC 3ro1'.i 60J1e3HH [Vogel .Iact al., cI11lTC
feHbI JHJarev HCOOhl'll-lbl IlC 3prC11,Hra110 Cl30eMy ,D.eHCTBl110, HO H ITO CBOCli CTpyK'rype. 0HJI COCTOHT II3 }J_BYX 3K30HOB -
CMblCJJ013L!X HYI<JICOTll;'l.111,IX 110CJICJl,OJ3aTC.TlbHOCTeH, BJlJA,CT[ )I<eHllblX Ha 3H3LHJTC.1lh!IOM pacCTo51m111 Jlpyr OT Jlpyni. 06pa-
3Y!OITl35IC51 npH HX rpaHcKpHirnJrn MPBK (11epBHLIHL>llf TpaHc-
1<pmn) ,n.Ba)KJl.bI JA1IJpBHIp1I<lnn63H1)J50IXBpaX6nJ6H<palaaTHAa
npoMC)l{YT0HlllblH cerMCHT Bblf)C33CTC5I H K0,[l)ipy1ouu1e llOCJle J(OB3TCJibHOCTJl COC,l1.HH5110TCH. 0Jl.Ha!<O 1303MO)l{H0 o6pa30BaHHe MPHK npH rpm1c1<pH1II(1111 mllllb o;u1oro 9K'.lOHa KHJraTaKaH MPHK IIOABC[lracrcH J1111111, OJlllOhfrnTHOMY c11.!JattcHttry, O}lHa K0 Olla cnoco6na 3KCI1pCCCllf)OB,!ThC}l C o6pa30133HHCM Tpy61
TOH (jJOpMbI 6eJII<a Tat, Koror>.IH TOI HC MeH('c 06.irnJI,aeT (t)y111< K6A6I6p-aKTHBnocTL>IOYpA01a 0cKCrbpcapct InoHpBI1IloC
reH rev, 1<aK H JHJMacocro,n 113 ;wyx 31,301108, nnalIAaMPHK JlOJJ)KHa no,usepraTbC51 )],OOHHOMY cnJlaAc1111ry. BrYpnpHBOJl.HT
K H36HpaTCJ1bHOH aKTuBau,11n c111ne3a npyKTYPHhlX 6e.IJKOB
B114, na rro3J!HCH cia11JIH HH<pcKUHH 3aMeJJ..JJHH cmne3 peryJIH ropHb1x 6eJII<OB. 3TO Jl.dicnrne pcamnyeTrn 6J1aroJI,apH yc1rn peHH0MY rpancnopTy il LLUTOII.na3MY Il0JlH0pa3MepHblX, BC cn,1ai'!cupoBaHJJI.,IX IIJIH O,!lHOKpaTHO CfJJHl!ICttpooamiblX MPHK. KO)],Hpy1ouu1x CllHTC3 crpywrypHblX 6CJII<OB, 13 TO 13pCM5I KaK TpaHc1rnpT B !lllTOfIJJa3MY J!Ba)l{J:LhI crwaikupoBaHHblX MPHK,
KO)],Hpy1ouu1x CHHTC3 pcryJTHTOplibIX 6CJ!KOB, 3aMe,llJI5ICTCfl H npeKpam,aeTcH 1cCnl1pcTpct CpoOpBIKIleCTairnM 06pa30M, Rev
0./IOKHpyeT 3KCrrpeccmo CBOero co6CTBCHHOl'O HpMIa6areHa tat
T,aa
:rn!OTC51 BHpyccrreuJHjHI'IeCKHMH ll KJleTOlJHb!Mll rrpoTea3aMH Ha IIH,l]J1Bll,UYaJll)HblC cpyHK1UIOH3JlbIII,IC 6c:11rn. 13eJIKH gag H pol mtpe33!0TC51 BHpyccrreumjmtJCCKOi;, ac11aJlTIIJIOBOH rrp0Tea3oif, KOTopa51 C3Mcl 51BJI51eTC51 rrpo.uyETOM n.:Ha pol, a 6eJIKH env 11ape3aIOTC51 KJieTO'-IHOH, ITO-BH,UIIMOMY, TjlllllCHHOITO,UOOHOH upo Tea3011. CTpII 3KCI1pCCCIIII reua pol IIJ)OJICXOJUIT pH60COMaJib Hbl11 C,UBHr paMKH Ha - I IIYKJICOTll}l, I3 pc3yJibTaTe CHHTC3II pyeTC51 6eJIOK-rrpe.u111eCTBCIHIIIK gag· -pol C MOJieKyJrnpHOI1 Macco11 160 000 [Jacks T. ct al., 1988]. ,UaJ1bHe11m1111 rrpouec CHHr ocymecTBJ151CTC51 rryTeM II,lpc:i;rn1[51 rrpe.u111eC'meHHHKcl IlIIpyccrreuncpw1ecKO!l npoTca:rni', C MOJieKyJJ51pHOl1 Macco11 9000-1 I 000, KOTO[)clH OTlllCII.Jl}ICTC}I OT 5'-KOHI(a pol B pe3YJibTaTe ayTOK3T3JIIITJl'ICCl(Ol'll llj)Ol_(CCC,t. llp0Tea3a Hape3a CT gag p55 Ha 6eJIKII p24 II p15, a pI5, IIaXO,U51I.IJ,Hl1C51 Ha
C-KOHUe rrpe.u111eCTBeHinIKa, Hape3aCTC51 Ha HYKJieoKaIICHJUlbie |
6eJIKH |
p9 II p7 [Mervis |
R. ct al., |
1988; Veronese F. ct al., |
I988]. |
!1p0Me.1KYTO'II1L1i1 |
IIJ)OllYKT |
IIape3aH1rn gag rrpe.u111eCT |
|
|
|
|
neHHHKa p39 !3bl5113JieH I3 /1,BYX c]iOpMax, O,UHa |
113 HHX |
o6pa3y |
CTC51 K3K rrpo.uyKT IIpouecc1rnra C C-KOIII_(a |
p55, a |
.upyra5I |
coorneTcrnyeT N-KOHUY [Mervis R. |
ct al., 1988]. D. Gowda |
11 coaBT. (1989) o6Hapy.tKHJIII T[)II |
IIJ)OMC.tKYTO'IHbIX |
cpopMbl |
n rrpouecc1mrc rro.11II11poTc1uL,l g·ag·---p4la, p4lb H p39, rrp11 3TOM p4Ja II p39 01,IJIII MIIJ)IICTl!Jlll[)Ollallbl II COOTBCTCTBOBaJIII N-KOHIJ,y MOJJCKYJlbl p55, ,l p4l !J COOTBCTCTBOBaJJ C-KOHUY-
JVibi H3YlJclJIH rrpcmecc1rnr 110.Jillll[)OTCll)lcl gag rryTeM HC I10Jlb30!3clHH51 peKoM6IIHclHTHOro 13IIpyca OCIIOBaKUIIIILI, CO/-lep
.tKaI.IJ,ero reH gag II 3KcrrpeccHpy1onLero noJrnrrpoTeH,U p50 [13yKp11HCKIIH M. 11. H JlP-, I986]. JlH3aTbI 3apa.tKeHHLIX KJie TOK CMeillHBaJIH C 6a1nepuam,llb!M JIH3aTOM, co.uep11rn11u1M pe KOMOHHaHTHYIO 11pon',13y B HLI- I, npoJLYKTLI rrpoTeOJIHTII'-Ie cKoro Hape3c1Hil51 gag a11aJIU:lllf10BaJlll C flOMOlll.bIO 11MMYH06JIOTHHra H pa,UIIOHMMYH011peI(IIIII1TaJ(IIII. Y.tKe '1epe3 30 MHH HHKy6au1m fl051BJ151JJacb IIJ)OMCll,yTO'Illa5! cpopMa Hape3aHl1}I upeJllllCCTBeHIIHKa p39 n Llll}lC Mcl}KOJ)IIOro, a 113CTO e/UlHCT-
13CHHOro KOMrroHeHTa gag. I Ia 60J1ee noJ,UHHX cpoKax |
rrpo11c |
XOJLHJIO Hape3am1e |
p39 Ha 3peJ11,1e m1pyrn1,1e 6cJIKII gag |
[Buk |
rinskaya A. G. et |
al., |
I 990]. |
|
npouecCIIHr 6eJIKOI3 |
gag BKJIIOLJaeT I3 ce651 MHj)HCTIIJI!lj)O· |
BaH11e MOJ1eKyJ1 gag H q1occpop11:mponaHHe p24 H pl7. M11p11cT11J111poBa1111e p55 ITJ)OHCXO,UHT rryTeM np11coe,UHHe111151 MHp11-
CTIIJIOBOI1 (.tKllj)HOH) |
KlICJIOTbl KO BTOj)OMY OCTaTKY rJIHUHHa |
C N-KOHIJ,a. CMbICJI |
MHp11CT!l,1HpoBaHH51 He conceM 51CCII, HO |
|
7 |
011eBll,UHO, lfTO 3TOT npouecc ,UOJl.tKeII IIMeTb 60JibillOe :rna11e m1e, IIOCKOJibKY MllpHCT!lllIIponaHI1e N-KOHUa 6eJIKOB gag 06uapy.tKeHO y 60J11, 11111HCTBa peTpoBIIpycon [Veronese F. et al.,
M11p11crnJI11poBaHHbIH N-KoHeu: 6Jiaro,napH rn,npocpoo HoMy B38HMO,nei'!CTBHIO C JIHl111,I!_aMil KJICTOlJHOH MeM6paHbl MO
.iKeT BbIIIOJIHHTb (j)y1mu:mo MeM6pmrnoro HKOpH, IIO)LBCllIIIBclH npe)J,llleCTBCHHHK gag K I1Jia3MaTIFieCKOH MeM6pmre KJieTKII. Bo3MO.iKHO, MHpHCTHJIHpOBaHHe HBJJHeTCH CIII'HclJIOM ,Il_JIH BHyT pIIKJieTOlJHOro TpaHcnopTa npc,nweCTBCIIIIIIKa K I1,1a3MaTIIqe CKOH MeM6paHC, Il 3TOT npou:ecc ne,neT K ,I!_OCTIUKCHIIIO KpIITil lJeCKHX KOHU:eIITpau:IIn MoJieKyJI Ha MCM6pc1I1c II c6opKe B11pyc Hoi'I lJaCTilU:bl. 3aMeHa OCTaTKa rJIHU:HHcl B npe,nllleCTBeIIHIIKe gag B MeCTe nprmpenJieHilH MHpilCTilJIOBOH KHCJIOTbl npilBO,Il_IlT K OTCYTCTBHIO MIIpHCTHJIHpOBaHHH Il IIOJIHOH 6JIOK8,Il_C cpopMil·
poBaHHH BIIpycHbIX CTPYKTYP Ha KJ1eToqH011 noBepxHOCTH [Got tlingcr THoet apaHeoHnHcCi
JlHllib npil MIIpHCTHJIHpOBaHIIH npc,nllieCTBCHHilKa gag, 06ecne1IHBaiomeM BHyTprmJicT01rnbIII TpaHcnopT II 3aHKopHBa HHe B MeM6paHe, MO.iKeT ocymecTBHTbCH npoTeOJIIITilqecKoe Ha pc3aHHe npeJJ,llICCTBeHHHKa Ha cpy1mu:noHaJibl-Ibie 6eJIKil. TaKHM o6pa3oM, CI3H3bIBaHHe C IIJlcl3MaTllllCCKOH MeM6parrni'i, o6yc JIOBJICHHOe MHpHCTHJIHJ)OBaHIJCM npC,LlllICCTBCHHHKa gag, HBJIH eTCH nepBblM 3BCHOM BO BCCX !10CJIC)LYI0IJUIX npco6pa30BaHHHX npII cospeI33HIIII m1pyc1-1011 1JaCTlllJ,hl. HaKoHeIJ,, MHpllCTHJIHpO BaJIHC MO.iKeT 6h!Th Ba)KHhIM ,Il_JIH I101IKOBaHHH BHpycHbIX qa CTHIJ, C KJieTOlJHOH TIOBCpXHOCTH, o6ccne•mBaH MaKCilMaJibHhlII KOHTaKT cep,nIJ,eBHH C H30rHYTOH nonepxHOCTblO nJia3MaTHIJe
CKOH MCM6paHbl co BCTpoeHHbIMH BHpycHhlMH I'JIIIKOTipOTeH,na
MH [Schultz ceHiRein cTHiHH6HyBi
PoJih MHpHCTHJI1Ip0B8HilH BO mry-rpmrncTo•IIH)M Tp8HCI10p Te 6CJIKOB gag H c6opKe BIIJ)YCHblX lJaCTlIIJ, IJOKasaHa II ,Il_JIH ,npyrnx pcTpOBHpycoB. HeMI1)1HCTIIJilIJ)OBaIIHLIH npc,nllICCTBCH HHK gag BHpyca MhlllIHHOH JJei'iKCMHH (oHKOBHpyc TIITia BHM He yqaCTBOBaJI B caMoc6opKC, IIC !10,Il_BCpraJICH npoTeOJIIlTH qecKOMY npouecc1rnry Il He BKJIIo•raJICH B n11pycttbre qacn1ubr. HeMilpHCTJJJIHpoBaBHhlH npe,LlllICCTBCHHHK gag OHKOBIIpyca TH na Ha!10,Il_BepraJICH caMoc6opKe, HO 3TH CTpyK'rypbl !IC Tpc!HC· nopTHpOBclJIHCb K KJICTOlJHbIM MeM6pc1HaM, a 06Hc1py)KHBaJII1Cb
B IJ,HTOnJrasMc1THIIecKHX A-•iacnruax [Rhees CeaMHunter OTp
MHnJIOi
MIIpHcTHJIHpoBaHHe p24 eBKCoocymccrBJrneTcH np11 3KC·
npecCilH rcHa gc1g KaK B 3yKapHOTH1leCKHX CilCTeMaX, BKJIIOqa51 ,npO)K)KH [Bc1thurst OaoKoMal., MH6HIaiTclK 11 68KTCpHaJibHbIX CII·
CTeMaX [Hansen OpoKHMal., HaH6ncgi11 n KJieTKclX HaCeKOMbIX Hpae3c1pc1)KeHHil peKoMfoIHaHTHbIM 6c1KyJIOBHpycoM [Delchamb rc M. et al., IInIIiBi.3TO CBH,neTeJibCTBYCT O npaBHJibIIOM npo ueccHHre peKoM6IlHaHTHOro 6eJIKa. Do HallIHM ,naHHblM, B KJICTKaX noqeK o6e3bHHbl, 3apa,KCHHb!X peKoM6HHaHTHblM BH-
Hape
pycoM ocnoBaKI.I,HHbl, KOTOpb!l1 CO,ll.ep:»rnT reH gag, rrpaKTliqecKH BCC MOJICKYJJbl peKOM6HH3HTHOro 6C.11Ka CB5!3bll33!0TC5! C KJ1t T011Hb1Mlf MeM6paHaMII. fipII CM0llJHl33HIIH J1!133Ta 3apa)!{eH llblX KJJCTOK C J1H33TOM 6aKTC()H3J1bHblX KJICTOK, 3KCrrpeccH PY!Oll.I,HX np0Tca3y B114, npo11cxo,ll.11T KoppeKTHOe IIape3aHHe npc; wecTBCHHHKcl gag C o6pa30133HIICM npoMe)!{yT01lHOI'O rrpo J YKTa 1-iape3am151p39 H 6eJJKOl3 cep,ll.llCBHHbI [Bukrinskaya A.G. et al., 1990]. B KJICTK3X, l!aCCl{OMb!X, IIH(pHll,HpOB3HHblX pe KOM61IH3HTHbIM 6aKyJ10B11pycoM H 3KCil()CCCH()YIOIUHX rrpe,ll. lllCCTBeHIIHK gag, nocne,ll.IIHH T3K)l(C 6bIJ1 CB5!3aH C KJ1eT011Hbl MH MCM6paH3MH, HO rrpH CMCll!HB311HH C JJH3aTaMH KJJeTOK, CO,ll.ep:»<al11,HMII peKoM6nnaHTIIYIO npOTCa3y, JU!Uib ne60JJbllI35! 11acTb MOJJCKYJI gag l!OABcpraJiacL Hape3a11mo [Overton H. et al., 1989]. 3TO MO)KCT 6b1Tb CB5!3aHO KaK C HC,ll.OCT3TO'IHOH aKTHBHOCTblO ll()OTC33bl 11 HeOTITIIM3JlbHblM11 YCJJOBH5!MH ee <f)YHKI.I,IIOHIIpOB3HH5!, TaK, CKOpee, H C HC,ll.OCTYIIHOCTbIO 60JJb weH qacrn MOJleKyJJ npe,ll.wecTBeIIHl!Ka gag ,ll.JJ5! npoTeOJJHrH ljCCKOI'O Hape33HII5! 113-33 HX ll3MeHeHH011 KOmpopMaI.I,HH.
XOT5! 6()jlblll35! tJaCTb MHpl!CTIIJJHpOBclHHblX MOJJCKYJJ npe,n_ lliCCTBeHHHKa gag CB5!3b!B3CTC5! C KJJCT011Hb1MH MeM6paH3MH, 1!3CTb MH()HCTHJIII()OBaHHbIX MOJICKYJI 061rnpy)!{HB3CTC5! B BH,ll.e aMopqrnoro MaTcpH3Jlcl Il KJICT01lll0M ,[)rpe II ll,HT030JJC [Luc
kow |
V., Surn111crs M., I 988; |
Mi Ilcr L., 1988]. |
ITo-BH,ll.HMOMY, |
,ll.Jl5! |
Tpancuop- |
a MOJICKYJI !( |
IJ, la3MaTl!tJCCKOH |
MCM6pa11e Hy |
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r |
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l |
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meH Cl11,C O)UIH )lOlIOJIHllTCJlblll,u'.i C!JI'll3J1. TpaHU!OpT gag B KJJeTO'IIIOC 51,Q[)O MO)l(CT 6bITh 06'b5!CHCH na. H1!HCM cne1 HqHI qecKOH CJlrHaJJbHOH nocJJC,ll.OBaTeJJbHOCTH, COCT05ll11,C11 H3 oc HOBHLIX aMHHOKHCJJOT, Ha N-KoHuc MOJJeKyJJLI. '.:ha nocJie,ll.o BaTCJJbHOCTb, HBJl5!IOII1,3HCH HYKJICOq)HJlbHblM CHfH3JlOM, 13b!CO· KOKOHCCpBaTIIBHa )lJ151 BHLJ-1, BH4-2 II BHO H BCTpc1-iaeTCH 13 6eJJKax Apyrnx 1mpyco!3, HMC!Ollll!X H,ll.ep11y10 JIOKc1JJH3311,1-110
[Dechambrc |
M. ct al., |
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1989]. |
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B11pycttb1fi |
6eJioK |
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CurnaJlbHa!I |
nocJ1e,I1,0BaTeJ1bllOCTb |
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BoJ1bUJor1 T-aHTHreH OB40 |
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p |
p |
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I( |
K |
K |
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R |
[KI |
V |
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VP213 BHpyca noJIHOMhl |
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p |
Q |
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I( |
K |
I( |
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R |
R |
L |
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.Il.f-lK-cB!l3bJBaJOw.Hii 6eJ10K |
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72 000 a,n.e110CTttpyca |
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A |
R |
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K K K |
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K I I( I |
R |
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flpe,n.wecrnemrnK gag: |
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K |
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R |
p |
0 |
G |
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I( |
K |
K |
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y |
I KI L |
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H |
BJ:14-1 (Hxb2) |
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BH4-2 |
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R |
p |
(} |
G |
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K |
I( |
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y |
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JI |
BHO BK 28 |
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R |
p |
G |
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I( |
K |
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y |
M |
L |
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K |
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H |
llpoMe,KyTo<rnaH cpopMa 11ape3ainrn rrpe,TI.wecrneHHHKa gag, |
6eJIOK p39, KaK n |
p55, co,!1,cp,1<aJ1a HYKJJeoqrnJJbHhIH cHrttaJI H |
061rapya<HBa,r1acb |
B 5!/lpe 3apa:tKN!HbIX Iu1eTOK [Bukrins |
kaya A. G. d al., |
1990]. HaJil1'IHe HYKJ1eocjrnJ1bHOro CIIrHaJJa |
yKa31,macT Ha N-KOHU,eBoe pacnoJJ011<eIrne 6cJ1Ka. Eemrn p24 H p17 ct>occpop1rnupoBaHbl TOJihKO y Bl-F-I H3 Bcex perpomIpy· COB. B TO >Ke npeMH oc11oottoll 6eJIOI< HYKJ1e0Kancu,aa tjiocqJo
j)HJrnpooaH y TaKHX, 000J10qe1rn1,1x PI·Il(-co,IJ,ep)l<am11x- Bllpy·
COB, KaK BHpycbI BC,HIKy.rnpHOro CTOM3TIITa II rpmrna [Kist ner D. et al., 1989]. GcM>l< p24 Bl,1Lf q1ocqiopH.rmpoBaH no
OCTaTI<aM cep1ma II Tpeomma, npH 9TOM q>octj>OpHJ!HpoBaHbl
JJHUJt, ,usa KOMnoHeHTa 6eJ1Ka H3 4 ero cocTaBJrnIom11x: b 11 d, HO He a H c (CM. HIDl<e) [Laurent A. et al., 1989].
BeJ10K p24 ren.:poreHeH rro rnoe1v1y cocraBy. TTp11 aHaJJH3e ero MCTO)l,OM H309J1CK'l'J)O(j)OKYCH/JOBIO-J o6HaPY)KCHbl 4 KOMil0-
1-lCHTa a, b, c n d c H303J1eKTpl-l1JecIHfMH TOLII<aMH COOT13CT crneHHO 6,8; 6,6; 6,5 11 6,3. KoM noHeHThl c n d HMeI0T MCHb
myI0 110,ll,BH>KHOCTL 1IpH 3s1CKT()O(jJOjlC3e B TJAAr, lJCM a H b, 803MO)l{H0, Jl3-3a pa3HOH CTCfICHH cjJOC(jJOJ)}IJIH/JOB8HIJ51 MOJJC Ky.'1. Cy; b6a 3TIIX KOMl10HCHTOl3 13 3apmKeJIHOii JUICTKC pa3- nast: J!Hlllb KOMilOHCH'J'bl a H b BKJII01JaIDTCH B aupnoH, B TO Bj)CMH KUK C I[ d IUlfHTJ Y C HeKOTOphlM KOJJlfllCCTBOM a H b OCT2IDTCH B HIHjHII.1,llj)OB/JJ-II-!Olil<JICTKe, H2XO,UHTCH B paCTBOJ)H MOfi (j)OpMe H ceKpe·nIpyI0TCH C KJJCTOl.JHoii IIOBC()XHOCTII 13 KYJibTY!HlJJbtty10 cpc,IJ,y [Laurent A. ct al., 1989]. TaKHM o6pa30M, BCC 4 KOMIIOHCJlTa p24 H3XO,lJ)ITCH Ha KJJ('T()l.JHOfi no
nepxHOCTH, !TX 11p11cyTCTl3HC |
A01(333JIO C |
IIOMOlllhlO MCTKU |
[ J 1l5J llOBCj)XIIOCTHUX 6CJIKOB |
3apa:iKCllIIOfi |
KJICTKIL CJICJlYCT |
OTMCTIITI,, lff() rrptt ;1,pyrnx J)CTJ)OBUpycm,Ix HII(j)CKl(IIHX crpyK-· TYJHlh/C 6eJfKII ccp,L L(CDl!Hbl He Ilbl,Qe.rrn.:IHCb Ha IJOBepx11ocT11
1-1mj:>m 11poBaHHbIX KJICTOK.
)KCIIOHHpoBaHI!e MOJICKYJJ p24 Ha IIOBCJ)XHOCTH 3apa)KeH Hl,lX KJ!CTOl( MO)l(CT IIpllBOJ(IITb I( Q)OpMII/JOBclHIHO gag·-cneI(H
qrntICCKOro KJlCTO•lllorn IlMMYHI-JOro OTBCTa J! aKTHnau1111 l{HTO |
TOKCH•iOCl<IIX |
T-JIHMcj)ouwroB. |
113 3TOro CJIC/lYCT, 11TO p24 HB |
JIHCTOI 6e3yCJIOBHblM KaHAH.UUTOM (ttapHJI.Y |
C cnv-6CJII<3M11) |
J |
H |
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1 |
nponrn |
Cl !HJ],_ |
Gcj10K |
p24 |
o,u11H |
fl 1 |
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BKJI!OtreHHH B B<IKL(11-1y |
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tt3 |
H8H60JJee |
ttMMyHoreHHblX |
CTJ)YKTypttbIX 6eJIKOl3 |
BHl..J. |
B1,1- |
coKIIe nlTpbl 3HTHTCJI nponrn p24 perHCT[Jllpy10TC}l y>Ke Ha paHHHX CT8;lH51X nou1c 3apa)l(CHHH, II 3TH aHTHTCJJa CJJyi!<,lT B8iKHblM cepo.11orw1ecKHM MapKepoM HH(jJC!(J]Jfll. CyruecTByCT ,rnppemUJ,H5l MC)!{JJ,y TIITJ)OM 81-fTIITeJI npOTill3 p24 II KJIHHll'le CJ(l!MH npOHl3JleHI-rnMH m1cpeKu1m: nptt HapacTaI-IIIJI J(.[flilllIIJ0- - CJ<HX CHMilTOMOB KOJIH'IeCTBO 3HTHTCJI BpeMCHHO yMeHbWaeTCil
[Kitchen L ct al., 1986; Cao Y. cl al., 1987]. YTpaTa .3TIL\
aHTHTCJI c noHB,TJeHHCM I.I.Hp1<yJ1npymuLero B KpoBH p24-ainn reHa H yMCHbme1rneM 11HcJJa CD4+-KJJeTOK HBJIHCTCH IJCTKHM KJ!Ulll!LICCKHM MapKepoM, CBH,UCTCJll,CTilYJOIIUIM O nporpeccHpo
BaHJHI 11mj:>e1rn,1111 |
H |
nepCX0)lC |
ec ll3 |
cy6KJ!l!HIP-!CCKOH CT3.UH!l |
13 K.rrnm111eCKy10- |
[de |
Wolf F. |
ct aI., |
I 988].. He MCHbmec 3Ha- |
11e1111e HMCCT CIHDKCHHC T!Hpa JHTIITCJJ 11ponrn p17 {Lange J. ct al., 1987]. ITo 3THM MapKL'paM y,aal33Jl0Ch npeJlCK33aTb npo rpcCCH])0B3HHC 3360JICB3HIIH 13 80% c.r1y1raeB HI-Jcj)CKU,IIH. YMCHbWCIHIC n!Tpa 3HTHTCJI M0)h'.CT 0b!Tb o6yCJJOB,ileHO tj)op M11p0B3HHeM HMMYHHhIX K0Mll.!ICKC0ll ll[lH llllIJKYJIHllHH B l(pOBH 6eJ11rn p24, CCK])CTilpyeMorn : ap;DJ(CIIIIl,IMII KJICTKaMH II 0CB06oiKJl3CMOro 13 Rp0ll!I llj)ll )lCCTIJYhUIIII llll[lll0II0B (cM. ])IIC. 6) [Buhrinshaya A.G., Sharova N. K., 1990]. lfa 3TOro CJIC/lYCT, 1ITO 6eJIOK p24 HrpaeT IICM;J.110Bcl)l{Hy10 p0.JJh B na1orc1-1c3e CITl:1f.l, H H3ytieHHe 11po.ll,y1rnHH 11 npoI.I.cccHHra 6eJ11rn cyrue c1BeH1-10 .ll,Jl5l TI0HHM3HHH MCX3HI-I3M3 m-1cjieKUHOHHOro np0llCC ca. HeMaJJOIHnKcH rtrnKT, lJT0 p24 11 p 17 3l(lcjJcKTHBHO 3Kcnpcc cnpy10TcH Ha KJJCT01IHOiI nonepXH0CTII II, 06.na,'l,aH BblC0KOHM MVH0fCHHblMII CBOHCTBaMH, 51BJI5110TC5J «K3HiUI)l_::JTaMII» Ha
13 Jll01!eHl1C HX B BaKUHHY ll(WTHl3 Crll-'f):L,
B npone)leHHbIX 11aM11 orn,nax 11pn :iapaJ>KCHHH BI1l.J 1rnc T0K Jurkat-tat II I19 M1,1 061rnpy,1<1m,rnn 6eJIKH gag 3apa)KaJO mero B11pyca K:JI, BO <jlp:il(llllll K.IICT01lllh]X MCMopaH, T3K 11 l(JleTOtJ!JblX H](IHIX. )lJIH ll}lCIITll<j)JIKa!lllll 6C.!IKOB C 110M0lllb!O
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HMMYHO0JIOTHHra |
IICII0.!lb30Ba.1111 |
ccp0JI0:311TIHlHblC |
CLIB0J)0TKII |
HllcjJHUHP()BaHJ-JblX |
JIHll H M0H0KJ!Of-l(ljll,llble arITllTC.1a. Y:;Ke 11e |
pe3 40 MIIH 6eJTKI{ gag, p55 II |
p39 6b!JIH Bb!HDJICHbl 13 01111- |
IILCHHblX l(JJCT0lJHJ,IX 5UlPax, K0,Jlll4CCTB0 HX |
yneJlll'IHB3Jl0Cb K |
2-My 'lacy TI0CJlC 3apame1111H. |
fieJIOK p24 |
Uh[JJ |
o6Hapy)KeH |
BO (jlpDI<Ullll MCM6pan II B 0TMblBal0lllCM H}tpa Gy(jlcpe, C0JlCp- |
1K3Il(CM I% |
Tp1n01ia X-100. B HJtpax Gw1a 1ra11;1cHa nco6u,, |
HO BbIC0haH |
h0HILC'IITpa1urn 6cJJl(a pl7. Tpa1Ie1101n n 5l}lpo p17 |
11 pl7-COJlCJ)}Kamnx npe)lJLICCTBCHIHIE0B, HO IIC p24, lIOJlTBCj)}!{ )laeT Ham14HC l(aflHO(!)llJ!J.,HOro CHl'lltlJla Ha N-KOIIUC pl7. 3TOT MaTpHKCHhllf 6e,TJOI{ M0)KCT Hrpan, po.'lb B HJlCpH0M Tf)attcnop
Te npom1pycH011 JI.HK u cc coxpa11enn11- n H.ll,pax llO mnerpa llHH B 1rneT01myro JI.HK [Sharova N. K., Bukrinskaya A.G.,
1990].
5eJIOK p24 llb/C0K0IIMMYH0I'CHCI!. Ha cro IIOBCpXII0CTli ua X0.ll,HTCH .uoe, a B03MO)KH0, II ;3 3l!TllfCHllble o6Jl3CTII, TIpe;.1. CT,lBJlCHllhlC JI11He11HbIM11 3mno11aM11 fWindhcuser M. ct al., 1989],. Cepon0311THBHhlC ChIB0p0TI,H Wllf)0KO B3f)bHpyroT f!O cnoco6HOCTH pcan1p0B<1Tb C 3TIIMII yqacTKaMu. O]lH3KO, HMCH H0 C 3TllM 6eJIKOM Cl3513aIIbl Jl0)Kll()l]()JI0}l(l!TC,ilbHhie pC3Y.'U,· Tan,1 11p11 onpe.uc.11e111111:111-rrn(\'I n H<PA II IIMMyr106.1w11mre,
UO-Bll,11,HMOMY, B CB513H C BCTparrnaHIIeM KJJeTO'!HblX 6eJJKOB oc
HOBHoro KOMTIJJeKca fHCTOCOBMCCTHMOCTH H fl051BJJCHHeM npo THB HHX aHTI1TeJJ y HeKOTOpLix .III0,11,di: MHOroKpaTHO po)KaB urnx )KCHUIHH, ,nuu C TIOBTOpI-ILIM nepemrnauHeM KpOBH, ,11,0HO poe aurnpc3yc-HMMy1mm1 nJJa3MLI [Bukrinsky M. et al., 1988]. YMCHbllieHHe aHTIITeJJ nponm p24 e CLIBOpOTKC KpOBH 51BJJ51eTC51 Ba)KHLIM KJlHHHl!eCKIIM MapKcpoM, CBH,11,eTCJJLCTBYIO UIHM o nporpecCHpoeau1111 CTTH,U [Laurent A. ct al., 1989]. chOT q:JCHOMeH, TIO-BHJlHMOMY, 06n51CH51CTC51 o6pa30BaHHeM HM MYHHbIX KOMTIJJCKcoe c Mo.r1cKyJJaMH p24, HHPKYJJHPYJOUIHMH B CB060,ll,HOM BH,11,e B KpOBH npH ycrweIIHOH penmmau1rn BHpyca. EeJIKH uyKJJeoKanc11,11,a p7 n pG pacuoJJmKCHbI ua C-Kouue npe,11,UieCTBeHHHKa gag. 3To MaJICHbKHC OCHOBI-ILIC 6eJJKH, co ,11,ep)Kamuc ,n:ne KOIIHH KonccpBc1T11n11oro 6JJoKa Uuc - f11c, KOTOpLIH o6JJa,n:acT CBOHCTBOM CB513bJB3TbC51 C HYKJJeHHOBblMH KHCJJOTaMH [South T. et al., 1989]. MyTaUHH n 3TOH o6JJacrn y peTpoeupycoB uapyUiaIOT ynaKOBKY reuoMHOH PKK H npu B0,11,HT K o6pa3oeaIIHIO JICHHtjJeKUIIOIIIIOro m1pyca. HecMOTp51 ua ue60JJbllIHe pa3MCpbl, HYK,/ICOK3IICH,ll,Hh!C 6c.nKH 06JJa,11,aJOT H p51,11,0M ,11,pyrnx q:>yHKUHH, B TOM 'IlICJle cnoco6cTBYJOT ,ll,HMe pH3aUHH reHoMnoii PHK, lJTO HBJJHeTCH Heo6xo,11,HMbIM ycJJo BHCM ,11,Jrn BbITIOJmemrn Mc1Tpwrnoi1 <JJYHKUHH PHK n npoueccc o6paTHoii TpanCKpnrrum1 [Panganiban A., Fiori D., 1988aH Bo3MO)KeH ux KOHTaKT c 6eJ11<0M pl7.
EeJJKH pol - o6paTHaH TpaHcKpHITTa3a (MoJJeKyJJHpHaH
Macca ,11,Byx cy6neflHHIIIJ: 66 000 H 51 000), np0Tea3a |
(MoJJe |
KYJJHpuaH Macca 11 000) H 1111Terpc13a (Mo.ncKyJ151pna51 |
Macca |
34 000)- Hape3aroTC51 II3 |
nommpoTCH.L\a-11pc;_i:mccrncuu11Ka |
gag/pol c MOJJeKyJ1HpnoJ".1 |
Maccoi"1170 000. O6paTHaH |
TpaI-Ic |
KpHIIUHH Bb!TIOJlH51CT MHO)KCCTBeHIILIC <pyHKIUIH B CHI-!Te3e rrpo n11pycuoi'.\ ,UHK: rroJJHMcpH:-iycT Mm1yc-uen1, ,UHK ua MaTpH ue reuoMuoii PHK, 11cnom,:,y51 B Ka'lccrnc ,iaTpaeKH TPHK rn6pu,11,11aoBauuyJO c PHK, 3aTeM pc1:-ipymacT PHK 6J1aro,LJ.a pH HMCIOUICHC51 pn6011yKJJec1:-iuor1 H aKTHBHOCTH (noKa 3TOT rrpouecc HC,11,0CTaTOlJH() 5!CCH), HO npH 3TOM OCTaBJJHeT OJJHr0- p1160HyKJJeOTH,ll,Hy10 :-iaTpaeKy ,ll,JJ51 CIIHTC3ci nmoc-HHTH ,UHK. B coCTane BHpHoHa 11 6aKTcpnam,uoi1 3KcnpccCHpy1omeii: cu
CTeMc o6paTHa5! TpaHCKpHIITcl3a rrpcJ:(CTaBJJeirn ,11,nyMH IlOJJH neITTH]I3MH C MOJICKy,n51puoii Maccoi'.'1 66 000 H 51 000. O6a I!OJlHIIeTITH,11,a HflCHTH'IHhl ua N-KOHJ_i:ax, r,11,C CO,ll,ep)KHTC51 06- JJaCTb ,UHK-rroJJHMcpa3HOH aKTIJBH0CTH. Y nomrnenTH,11,a p51 oTcyTcrnyeT C-Koueu e 06J1acTH pn6m1yKJJea3bI H [Hansen J. ct al., 1988]. UcHTpaJ1b1Ia51 06J1acTb MoJJeKyJJLI o6paTHOH TpancKpirnTa3hl C0JieptKHT, noMHM0 ,11,Byx acnapnIHOBLIX KHC
JIOT B KaTaJIHTHlJeCKHX yi1acTK3X, «JieI1UHHOBYIO M0JIHHJO»,
