.ll,bmaeTrn 13 UHC 60.'lbHbIX CffHJJ,, r;ic sapa!l(CHHbie Bl14 MOHOUMTbl HrpaIOT po.lJh <<Tp<rn.HCR(ffO KOH5l», Tpancnopn1pyH aupyc 13 lUIC H 06ecneq1rnaH ero KonTaKT c 11ciipo11ttTaMH H Heiipornri:eA. TTpH BaKyOJ1Hpttofi MHe.11onanrn, nc,peqa1omeik,1 y 25% 60JlbHblX, o6napy)KJ1B3eTO! 11HgJHJlbTJ)3UHH MaKpocpa raMH 6eJJoro nemecTaa cnmrnoro M03ra. C noaepx1-1ocT11 MaK pocparoB rro111<y10TcH Bttpyc1-1u1c 1rncrnub1, a BHYTPH MaKpo<j)a roa BbIHBJIHIOTCH rJ11,161<H MHemma [Eilbott D. et al., 1989]. AKTHBHoe nepeBapHB3HHe MHCJIIlll:J MaKportrnraMH, npHBOJI,51mee K o6pa30BllHHIO BaKyOJICH II MlfeJIOTiaTHII, MO)J{eT 6bITh 06yc.r10BJJeHo CTHMy"1Hpym11tdi aKTIIDHOCTbIO nnpyca Jm6o ceK peutteif sapa)l<em11,1M MaKpocparoM <]>a1<ropoa, pa3pywa10mHx HepsHy10 TKaHb.
fJpOBHpyc B KYJlbTHBHpoBaHIIblX JJHM<pomnax aKTHBl-lpy eTCH npn J1,ei1CTBHH JJCKTHHOB, cpop60.,1orwx3<trnpoB, lll!TOKH HOB. AKTJ-rnau1rn npOHCXO.ll,HT rrpH JI.eHCTBHH Ha TIOKOHIUHCC51
JIHMqJOUl!Tbl BHpycnoro 6eJ1K3 gp120, Cl3 13b1B3Hl!e KOTopor-o C peuerrTOpaMH CD4 BhI3brnaeT 06pa3onamre qrnKTopoB Tpattc
KpHnUHH, np11B0/1_s:rnu1x K BKJ110'le1rn10 npmrnpyca [Kornfeld H.
et al., 1988].
AKnrnaumo npom1pyrnoti JJ,HK Mory-r BbI3bIBaTb H reTcpo JJOrn'-lHhie BHPYCbl II B nepny10 01,epCJlb supycu UIHOMeraJJHH, npoc-roro repncca II renanJTa B (CM. r.11any 6). Bo3MO)l{HO s OCHOBe aKTHB31UIII JIC)K.'."IT Te )Ke qiaKTOpb!. KOTOJ)bie ,ue(!CTl3YIOT H B CJJyqae CHJlbHhIX IIMMYHOfCHOB. floKa3aHO, 1!TO B CHCTCMC, co.L1,ep)Ka1nei1 3am1cHMh1Ii OT LTR BULf 6a1nep1rnm,r-rhri-iren CAT, OH 3KTIIBHpyeTCH np!I Tf)311C(jJOJ)M3Ulllf KJJeTOr< BTTr H uuT0MeraJ1m1. TpaHca1<THBauu10 cHCTeMbr LTR - CAT B OT cyTcTBHe 6e.1Ka Tat nul3hll3aJ1u cBepxpattr-me 6eJJrrn B11pyc2 repneca lCP4 1-1 n Me111,me11 cTenem, lCPO [Abrecht M. et al., 1989]. Do ,l.lauHhIM 1'lpyrnx aBTopon [Nabcl G. et al., 1988], noJryl\eHHUM B OTihITax Ha TOii )Ke CHCTCMe, aKT!lB3llll51 o6yc JIOBJJeHa KOM6mmpoBaHHLIM }leikTBHCM o60HX 6eJ!KOB. AKTII B3TOJ)bl .n.eikTByJoT Ha crreuncjrn1recK1111 y'laCTOK B114 J1,.rnmoii
B 73 nap1,1 HYKJieOTH/lOB B cocnBc yc11J111TeJJSI B 06JH1cTH U3 [Mosca J. et al., 1987; Lubon H. et al., 1988]. B ::nof1 )KC o6JJaCTH J-13XOJHITCH 3JICMCHT, C KOTOJ)hlM Il:-laHMOJI,el1CTByeT KJieTotrn1,rti 6eJJOK NF-xB. BsaHMo,1.1,ciicrn11e yc11.1HTCJist B co crane LTR c 3THM 11 ,upyrnMH HAepHLIMH 6eJJKaM11 K.rreTOLJHOro npmrcXO)R:.ll.eI-JHH npHBO,UHT K BJ<JII04elIHIOTpaHcKpHmom npo•
mrpycHh!X- reHOB. CJJe;'(OnaTCJII,HO, rrnpyclll,le H KJJeTOLJHI,Ie TpaHcaKTHB3TOJ)bl ;:i,elicrnyIOT Ha CT3/l.l1HTpaHcKpumurrr no
OAHOMY H TOMY >Ke Mexan113My. KaK H BO Mttornx Apynix cJ1y1rnJ1x Tpa11car<Tl1Ba1om, J303MO)KJ-Ibl 6CJIOK-UC.TJKOBbre B33HMO
.l.lelkTBl151 Me>K.llY snpycm>1MH H K.neTO'!HblMH 6e.TJKaM11-peryM1-
TOpaMH, CB513bIBaJO!llHMHC51 c llHK (Friedman eH1et al., Bcee KaK H nnpychI renaTHTa B H nponoro repneca, UHTOMera JJOBHpyc TaK)Ke cnoco6eH aKTHBttpoBaTb npoMoTop B114. Kai< H Bl'P-1, HHT0MeraJI0BHpyc nona.n.aeT B opraHH3M npH l10JI0BOM KOI!TaKTe, nepe.l!HBaJ--JHH Kp0BH, sepTHKaJJbHblM nyTeM - OT MaTepH K H0B0p0H<Jl,eHH0My. UHTOMeraJ10BHpyctta51 HHcpeK lll'.151 o6ttapy)KHBaeTCH 6oJJee T1eM y aHTKHKaTMrpynnb1 caMoro BbIC0K0f0 pHCKa -y fOM0CeKcyaJJHCTOB; B HX KpOBH Haxo Jl.HTCH aHTIITCJ!a nponIB 1.1,HTOMera.rIOBHpyca, a y MH0rHX BHpyc C0)].ep}KHTC5l B KpOBH H cnepMe. K Bttpycy l:!YBCTBHTCJlbHbl MHO· rne KJ1eTKH opraHH3Ma H B nx HrncJ1e T-JHIM<pOUHTbl. TaKHM o6pa30M, o6a Bttpyca nopa)l<a10T o.n.Hy H TY }Ke MHllieHb. BpH Ka3aHa aKnrnaum1 3Kcnpecc1m 6aKTep1rn.'lbHoro re11a CAT, ac cou1111posaHH0ro c npoMoTopoM HKTaTeMoIOe3T0M ooJJaCTb npo MoTopa B114, IHI KOTopyIO ,ll.CHCTBYCT 3KTHB3TOp, 0TJIHlJ3CTC51
OT 06.,iaCTH, C KOTOpoii [l3cl[IM0J].e!ICTByeT npo;1,yKT re11a tat [Davis 0a1r1 ul., ppyHbK1I1TaK, [ HTOMeraJI0BMpycHa}l IIHq)CK
UH51 M01KeT 11poB0UIIj)0Bi:l'n, clKTHBillUlf0 nponHpyca y 3apa )KCHHbJX ,llH!l Il ncpcX0;l OT U0CI!TeJlhCTBa K KJIIIIU\l!CCKHM rJ10p M3M CTTH,ll. 1lpyrof1 uptt1m1-1oi1 nporpeccuponamrn CTTH,ll MO ryT 6bITb HMMyHocynpecc1u1 H yMeHblllemre 0TH0UH:'HIHI T4 : T8, K0T0poe Bbl3blB3CT UHT0MeraJIOBHpyc.
Tpa11caKTHBaropoMnupyca rerraTHTa He51BJJ51CTcn npo.uyKT reHa X, KOTopbitt B3aHMo,Uei'icTByeT 06J1acT1-,10 xB s LTR npo
s11pyca, T. e. C TOl1 )KC o6JJaCTblO, C KOTOpoii CB513bIB3eTC51 1rneTOlfHb111 TpaHca1nHBaTOp NF-xB oMIpOJ. et al., HKaKBTO
TaKl!M o6pa30M, repnec, UIIT0Mcra.r.oBnpycHaH MH<peKUHH, renaTIIT B MoryT I{e T0JJbKO B03HHKHYTb Ha qioHe CTIH,ll KaK ormopTym1cTHL!eCKHe HHcpCKUHH, HO II IIH,ll.Yl HpOBaTb aK
THB3UHIO rrpoBttpyca, a TaK)!<C crroco6cTBoBan, rrpOHBJICHHfO
6oJie3HH 11 ee nporpeccnposam110.
fipH'IHHbl nt6eJIH JIHM<f>OU,HTOB u nospe)K)J.CHHSI HX <l>YHK UHH npu THa11,I(. B 0CH0BC 0OJibllJHHCTBa K,IIIIHlflleCKHX cpopM CTTJ1Jl JIC)KHT Il0CTeIIeirn0C YMCHbUJCIHIC K0JHitJecTBa Klll0aIC BbIX irneTOK HMMYHH0fO IIp0L ecca T4-JIHMcpOUHTOB ;11160 ,Ke npH coxpaHemrn HX u,eJJ0CTH0CTII rny6oKoe HapyrueHHe HX cpyHKUHlf. O,[lH3KO nponnpyc o6ttapyxrnsaeTCH Jlllillb R 04eHb HCMH0rIIX JJHM<pOUHT3X, IlpHMepHO TH 0,/I.H0M Ha C1o46TIo6 HH T3KTHbIX l<JJCTOK, H IIpH aKTHBJJ.J.HH npOBHpyca Hl-1cpeKI.I.IIOHI-lblH npou,ecc npoTeKaeT JIHU!b n orpam111eI-1110MKrncJJe T4-KJJeTOK, HC COH3MepHM0M C r.ny601<HM yrHeTeI-IlleM HMMYI-IHOH CHCTeMbl. 113 9TOro CJIC)lyeT, MIT0 Hapymeunc <pyIIKUIIII T4-JIIlMq)OUIITOB HeJJb351 O0'b51Clll!Tb T0JlbK0 ,Jl!UJ!b K3H0IHJLieCIU!Mll npwrnttaMn, c K0T0ph1M11 BHpycoJ1orn BCTpcoia10Tc5I npll JJ.pyrnx rrnpycuh:X mHjJeKUHHX. Oln1npH1IHHbl CJIC,i1,y1011u1e.
1. B3aHMO,Ll.eikTBHe c KJieTKOI'i: BHll MOiKeT rrpHBOAHTb K IIHTOJIH3Y, o6pa30Bamno ClIHUHTH51 HJI!I 2Ke ¢opMHpOBaHII!O JiaTeHTHOiI 1rncfJeK11,HH. MmKeT 6bITb H cMernaHHbIH 3<p<peKT, COlJeTaIOill,HH pa3Hble THIIhl IIHTOnanilJCCKOli aKTHBHOCTH (11,ll· TOJUI3 H CIIMDJiaCT006pa3osa1rne). THrr B3aHMo.11e11cTBHH o6yc JIOBJieH B OCHOB!!OM reHeT!!'IeCKIIMH oco6eHHOCT51MH B036y.1111· Te.Tm. B 06pa3y10m111IC5! Cl!Hll,IITHH BKJTIOlJaIOTC5!HC3apa)KCH Hbie ,'Il!MqJOL{HTbl, rrpn 3TOM K.l!eTKH B COCTaBe ClIHUHTII5! coxpamIIOT JKH3Hecrroco6HOCTb He 60J1ee 2 -3 cyT.
2. 3natlllTCJ[bHO yBeJ1lflJlfBaeTC5! Ilj)OHHUaCMOCTb IU!a3Ma TlI1IeCKOH MeM6paHbl npH rrpOiIYKIJ,HH T4-JIHMqlOUIITaMH 60JJb moro KOJJHlJeCTBa BIIJ)YCHb!X '13CTHU; KaK ll3BCCTJIO, c\KTl!Ba UH5! llJ)OBHpyca TIJ)HB0.1IHT K HCBU,Ll.cl!IH M TeMTiaM c6opKH lI IIOlJKOBamrn BHpycm,!X 113CTHIJ,.
3.BeJIOK CJIII5!HH5! gp4l no•my1ornHXC51 II speJiblX mrpycm,rx '!aCTIIU Bbl3bIBaeT HapyrneHHe IIJ)OIIHIJ,3CMOCTII I!Jlc\3Mc\TH11C CKOH MeM6paHbl KJieTOK.
4.Be,10K gp120, JJefKO OTJiaMbIBa5!Cb OT llOBCJ)XHOCTH BH pycnou •rncTHJibI, cnoco6en cB5!3aTbC5! c peuernopoM CD4 nH TaKTHOro T4-JJIIMqJOIJ,HT3 If HapyrnHTb ero cfJYHKlUIIO. 3To npH
BO,UHT K: I) 6JJoKHposam110 |
B3aHMO.lleifcrnH5! MOJJeKyJJ CD4 |
c MoJJeKy.1aM11 MHC Knacca |
II; 2) .11eqieKTY B rrocJJe,ny10u1,1tx |
ClffHa.r1ax, B '!aCTHOCTl! 11apymeHHIO IIJ)O.llYKill!H JllIMqlOKHHOB, HCOOXO,UHMblX Jl,JJH perym1u1rn HMMymroro OTBeTa; 3) HHJJ..YK u1m J)5!)l3 tjJaKTOJ)OB, HCOJJaronp1rnnIO .1IeI1CTBy1011u1x Ha KJICT Ky; 4) YBCJIIP!eHII!O BHYTJ)HKJJCTO•IHOfO ypomrn HH03HT0,1Tp11-
q}OC(paTa H Ka.1bl1JHI; 5) |
ycHJICHHOli |
3KCI1peccm1 peuemopOB |
,UMI VIJI2 11 Jlp. [Kornfeld H. et al., |
1988]. |
5. B3a11Mo,ueiicTBHe |
gp120 c pe11,e1ITopoM 11yncTBHTCJJb· |
HOH KJ1eTKH MO)!{CT Ilb13B3Tb IIC•IC3l-lOBeHHepeuerrTopa CD4 C |
KJICTOlJHOii nonepXHOCTH JIHM(jJOUH'ra, llj)HBO)l5111lCC K 6,'IOKHpo BaHHIO B3aHMo.11eifcTBH5! penemopa CD4 c MHC KJJacca I I 11 YMCHblllCHHIO 3KCrrpeccmr reHa HJI2. I1ocTerreHHa5! IIOTCJ)H peuerrTOJ)OB rrpH ycTaHOBJlCIHIH XpOHH'!CCKOTT HHqJCKUHII CB5! :rnHa c 11apyrne1rneM TpaucnopTa II J10KaJrnsaIJ,HH penernopmi H, B03MO)KHO, C o6pa30BaHIICM BHYTJ)IH<,'ICT011H0f0 KOMil.1eKca MCiK,uy peue1nopoM H npe,urneCTBCHH!IKOM 6e.TTKOB env [Ste
venson M. et aI., 1987, 1988].
6. BHll-nrnJ1eK1urn BhI3bmaeT uapymemie CTpyKTYJ)bI JIH m1.1IOB KJJCTOlJHblX MeM6paH H IIO)l_aB.1Clll1C CIIHTC3a cpoccpoJrn lIH,UOB [Lynn w. et al., 1988].
7. CBH3hIBam1e cB060.111-1b1xMo.1eKyJ1 gp120 c penenTopoM CD4 Hesapa,meHIIblX Jl!IM(jJOIJJ1TOB npenpamaeT HX B MUlliCHII
;urn .1IeiieTBHH Ul!TOTOKCl!lieCKIIX |
KS!CTOK. |
13 3aKU3 N2 1293 |
193 |
8. Jlmv1cpoUHTbl, Ha TI0BCpXH0CTH KOT0pb!X 3KCTI0HMp0BaHbl BnpycHblC 0CJJKH gag, env, nef H vif, CTaHOB51TC51 MHlllCHbIO ,[l,.151' Uf!TOTOKCJ11ICCKHX K.IIeTOK. TipH 3TOM cpy11KUMOHHpy10T pas JJH'!HblC THflbl UHTOT0KCHlJeCIU1X KJICTOK. J1HMqJOUHTbl, .9KC npCCCIIpyIOillJ!e 6eJIKH Gag, 51BJ15110TC51 MHlllCH51MH ,l1.J151 UHT0·
TOKcw1ecK11x .rmMcfJOUHTOB CD3+, CD8+, 3KcnpeccHpyrouuie 6eJ1Kn Env- ;urn K.rreTOK K II NK [Riviere Y. et al., 1989].
9. Y IIH(pllUIIPOBa1rn1,1x BHY: 06pa3y10TC51 ayToaHTIITCJia npoTHB co6CTBCHHOro aHTHre1rn - OCHOBHoro KOMTIJJCKCa rH CTOC0BMCCTHMOCTll (MHC) KolaCCa II.
B npouecce HHcpeKUIIH tJHCJJ0 T4-JIHMcpo1unoB yMen1>rna eTc51 IIOCTCTICHHO, H Bbl3blB3CT Y.L\HBJJCIIHC, TI0'IeMY HX K0JilfllC· CTBO He KOMIIeHcHpyeTC5I. B03MO)l{HO .9T0 o6b51CH51eTC51 sapa )l{CHHeM KJieTOK·TipenrnecTBCHIIHKOB H CTB0.HOBb!X KJICT0K, 1IT0 TIJ)HBO}l,HT K 0TCYTCTBI!IO TIJ)O/lYKILHH 3pem:,1x JIHMq)Oil,HT0B.
BH4 OKa3bIBaeT l]JITOII3TH1ICCK0e .n.eiicTBHe B OCH0BH0M Ha T4-JJHM(pOUHTbl, HO He Ha MOHOil,HThl II MaKpoqrnrn, XOT51 3T!I KJICTKH T3K)l{e HMClOT !Ia CBOeii IIOBepXHOCTH peuernop CD4 H BvfI-l M0)Ke·r npnKpenJI51TbC51 K HIIM II sapa}KaTh HX. O,nHaKO
.9KCrrpeccll5I MOJieKyJI CD4 B 3THX KJlCTKax 3Hcl'IHTCJlbHO MCHb· we, 'ICM B T4-JUIMqJOU11T3X. MoHOil,HThl, 6yJLylJH 0TH0CHTC.TlbHO ycToi'FlllBblMH K 11,11Tona1w1ecK0My JJ,eikTBHIO BHY:, 51BJI5110TC51 0CHOBHb!M pe3epByapoM BHpyca B opraHH3Me; BHpyc M0)l{CT Ee TOJ!bKO nepe2K.HB3Tb B 3THX KJICTKax, 110 H TpaHCI10pTHp0B3TbC51 B pa3Hhle TKclHH H opraHhl. TeM He MCHee ¢YHKil,HH M0HOJWT0B H MaKpocparos TaK:IB.e nopa2K.eHa npn Cfll1,U: Ha- 6.110;:i:aiorrn ,ueq)eKTbI XCMOTaKCHCa H (paro11,1ITapuoil: CTIOCO0· H0CTH 3THX KJJeT0K.
BeJlymeecR 1m1poKHM qJpOHTOM 11acTy1rne1rne Ha CfIH,U H nocry11aI01IH151 o6nmpH851 Hll(p0pMaUH5I He paCKpbWH Tclilll 3TOll cynepm1<j)eKUHH H TI0J)0.l(HJIH HOBI,le BOIIp0Cbl H H0Bble napa,u0KCI,I, KOTOpbie Tpe6y10T nepecM0Tpa YCT051BIIIHXC51 npe,ll, CT8BJICHHI1 0 B33HMOJJ,CilCTBlIH B036y,nHTeJI51 H opraHH3Ma. 3a ranoqHoe llOBe,'l,eHIIe m1pyca nocJiy)lrnJIO ,U3)1{C OCII0B3HHCM Bblp33HTb C0MHCHl!e, 51BJ151CTC51 m, OH HCTHHl!b!M B036yJ],HTe JleM CTIHJl [Duesberg P ., 1988]. ,Uei"1cTBHTe.11,Ho, npH BH4-1rncpeKUHH He Ha6JUOJJ,aeTC5I HH 0JJ:HH H3 3 nocTyJiaT0B P. Koxa: 1) s11pyc He Bbl51BJIKCTC51 B 60,rJhlllIIHCTBe c.rJyqaen HHlpeKUIIII; 2) Bnpyc M0)l{eT 6bITb Bbl,UCJICH JlHlllb nyTeM pe8KTHBclll,HII in vitro HCMH0f0IJIICJiel!Hb!X MITCIITH0 sapa:>Kell· HhlX JlHM(pOUilTOB cpe.nn MIWJJH0Ha He3apa)l{eHHbIX; 3) BHpyc He Bhl3h!B8eT KJllJIIIFiecKy10 cpopMy HHlpCKIJ.IIH npu 9KCI1CpH MCHTam,HOM sapa)l{CHHII IIIHMTl8H3e HJIH CJJyqafiHOM 3apa:i«:e HHH IJe.rroBeKa. K 1rncJiy napa,'l,.0KC0B. CB513aHHTiIX c no36y,;1H TeJ1eM, OTH0C5ITCH H xapaKTeJm1,1e JJ.mI CITH,U oco6eHHOCTH
11atotet-te3a: l) n otJJ!ILIHC OT KottneHJ..1JiaJlhHb1x HH<peK11,Hii. BH pyc DW3hlD8eT Gone3Hb nocne ycTaH0BJJeHHB aHTHBHpycaoro cocToRmrn; 2) 0Hpyccne11.11cj)111 1ccKHe awrnTeJra JJ.a)Ke B oqe11h Bb!C0K0M TllTpe, H3K311J1Rlla!0lll,HCC5l B CblB0p0TKe Kp0Bl-1 3apa
)KeHHbIX JIHU, He c11oco6I1bl HCHT!)8JJH30B3Th B11pyc; |
3) X0TH |
BHpyc B 11yBCTBl1TeJibHblX KJieTKax pa3MH0)KaeTC5l |
B |
Tel!eHHC |
2-3 )l.HeA, 6oJie3Hb HacrynaeT |
B cpe)l.HeM 11epe3 |
6-8 neT; |
4) rraToreue3 60JIC3HH o6wrno |
CBH3aH C rn6eJ1blO T-JUiMq)O |
[J.HT0B II B TO )Ke npeMB BHpyc nopa>KaeT rrpHMepH0 0AHY H3
105 T-K.'IeTOK, |
a 5 % |
JlllMcpOUllTOB pereHepttpyIOT B Te'ICHHC |
2 cyT. |
|
|
He MeHee |
38ft-l)l.0 |
1 !Hl>l II MOJICKy.1rnp111.,1e npoueCCbl, B03Hl1- |
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