Amanqwanqwa amaninzi afunekayo ukukhusela, ukuphelisa intsholongwane
Imbali yokuphuhliswa kwegciwane lesandulela ngculaza iye yaphawulwa yimithwalo emininzi kunye nokudumala, nganye ibonakala "yimpumelelo" ebonisa imingeni engakumbi kunye neengxaki zokunqoba. Ngokuqhelekileyo kubonakala ukuba kwinqanaba elinye abaphenyathi bathatha, isithintelo esingalindelekanga sibabuyisela ngenye indlela kunye namanyathelo amabini.
Ngandlela-thile, uvavanyo olufanelekileyo, ngenxa yokuba asikaze sibone umviwa ogonywayo.
Ngakolunye uhlangothi, izazinzulu ziye zenza iminyango enkulu kwiminyaka yamuva, ifumana ingqiqo enkulu kwiintsholongwane eziyinkimbinkimbi yokusuleleka ngu-HIV kunye nokuphendula komzimba kweso sifo. Oku kuphazamisayo le nto eyenziwa ngabantu abathile ngoku bakholelwa kwisitofu sokugonya kunokwenzeka kwiminyaka eyi-15 ezayo (phakathi kwabo, i-Nobel Prize leureate kunye ne-HIV-bafumana uFrançoise Barré-Sinoussi ).
Ingaba isitofu esinjalo siya kuhlawuleka, ukhuselekile, kwaye kulula ukulawula nokusabalalisa kwiindawo zokuhlala emhlabeni jikelele. Kodwa into esiyaziyo ngokuqinisekileyo kukuba inani lezithintelo eziphambili liza kufuneka lixazululwe ukuba nawuphi na umviwa oza kuhamba ngaphaya kwendawo yesicatshulwa.
Iindlela ezi-3 ezenza iHIV iqinisekise ukunyangwa kweNtsholongwane
Ukusuka kwimbono ebaluleke kakhulu, iinzame zokuphuhlisa igciwane lesandulela ngculaza ziye zaphazamiseka ngokwahlukahlukana kwemfuyo ngokwayo. Umjikelo wokuphindaphinda we-HIV awukhawulezi nje (iiyure ezingaphezulu kweeyure ezingama-24) kodwa ulungelelaniso lweziphambeko eziqhelekileyo, ukukhupha iikopi ezithintekayo ezithintekayo kwiintlobo ezintsha njengoko intsholongwane idluliselwa kumntu kumntu.
Ukuphuhlisa isitofu esisodwa esisinako sokuphelisa ngaphezulu kwezi-60 eziphambili kwiintlobo kunye neengxowa-zityalo eziphindaphindiweyo-kunye nakwizinga lehlabathi-ziba nzima nakakhulu xa izitofu eziqhelekileyo zingakhusela kuphela inani elincinci leengxaki zentsholongwane.
Okwesibini, ukulwa ne-HIV kufuna impendulo enamandla kwi-immune system, kwaye kwakhona kwakhona apho iinkqubo zingaphumeleli.
Ngokwesiko, iindili zegazi ezimhlophe ezibizwa ngokuba yi- CD4 T-cell ziqala ukuphendula ngokubonisa iimpawu zebulali kwindawo yesifo. Okumangalisa kukuba, ezi yizona iiseli ezijoliswe kwiHIV kwi-HIV. Ngokwenza njalo, i-HIV ithintela amandla omzimba okuzikhusela njengokuba inani labantu base-CD4 lichithwe ngokufanelekileyo, okubangela ukugqitywa kokugqibela kwezikhuselo ezibizwa ngokuba yi- immune exhaustion .
Ekugqibeleni, ukupheliswa kweNTSHOLONGWANE KAGAWULAYO kuphazamiseka yintsholongwane 'yokukwazi ukufihla ekukhuselweni komzimba. Kungekudala emva kokusuleleka, nangona enye i-HIV ijikeleza ngokukhululekile egazini, i-subset ye-virus (ebizwa ngokuba yi- provirus ) ingene kwiindawo ezingcwele ezifihlakeleyo (ezibizwa ngokuba ziindawo zokugcina izilwanyana ). Xa sele ungaphakathi kweli seli, i-HIV ikhuselekile ekufumaneni. Esikhundleni sokutshatyalaliswa nokubulala iseli yesistim, i-HIV engavumelekanga ihlukana kunye nomninimzi kunye nezinto zayo zofuzo. Oku kuthetha ukuba nangona ukuba i-HIV ihamba ngokukhululeka, i-virus "efihlakeleyo" inokuthi ikwazi ukusebenza kwaye iqale ukusuleleka kwintsholongwane.
Imithintelo Yokunqoba
Kuye kwacaca kwiminyaka yamuva nje ukuba ukunqoba le miqobo kuyakufuna isicwangciso esicwangcisiweyo kunye nokuba akukho ndlela enye iya kufeza iinjongo ezifunekayo ekuphuhliseni isitofu sokugonya.
Iinqununu eziphambili zeli qhinga liza kufuneka lijongane nazo:
- iindlela zokunciphisa ubuninzi beengcinezelo ze-HIV
- iindlela zokunyusa iimpendulo ezifanelekileyo ezikhuselekileyo zokukhusela umzimba
- iindlela zokugcina ingqibelelo yamasosha omzimba
- iindlela zokucima kunye nokubulala iintsholongwane ezilindelekileyo
Inkqubela yenziwa kwiinkqubo ezininzi ezicetywayo, kunye namazinga ahlukeneyo okuphumelela kunye nempumelelo, kwaye inokuthi ichazwe ngokucacileyo ngolu hlobo lulandelayo:
Ukukhuthaza "Ukunciphisa Ngokubanzi" Ukuphendula Ngomzimba
Phakathi kwabantu abaphila ne-HIV, kukho i-subset yabantu ababizwa ngokuba ngabalawuli be-elite (ECs) ababonakala benokumelana nokunyuka kwe-HIV .
Kwiminyaka yakutshanje, izazinzulu ziye zaqala ukufumanisa ukutshintshwa kwezinto eziphilayo ezikholelwa ukuba zinikezela kule mpendulo yemvelo, yokukhusela. Phakathi kwazo i-subset yeeprotheyini ezikhethekileyo ezikhuselayo ezibizwa ngokuba zi- antibodies (okanye i-BBbs) .
Ama-antibodies avikela umzimba ngokubhekiselele kwi-agent echaphazela isifo (i-pathogen). Uninzi lwazo aluyikuthintela i-antibodies, ebonisa ukuba babulala enye okanye iindidi ezininzi ze-pathogen. Ngokwahlukileyo, i-BBbs inamandla okubulala i-wide range of HIV-variants-up to 90% kwezinye iimeko-ngaloo ndlela iyanciphisa amandla okusuleleka kwintsholongwane.
Kuza kube namhlanje, izazinzulu azikwazanga ukuchonga iindlela ezifanelekileyo zokubangela impendulo ye-BNAb kumanqanaba apho ingaqwalaselwa njengendlela yokukhusela, kwaye ukuba impendulo enjalo ingathatha inyanga okanye nokuba iminyaka ikhule. Imiba enzima ngakumbi yinto esingazi ngayo ukuba ukuvuselelwa kwale bBB kungase kube yingozi -kuba ingaba isenzo ngokumelene neeseli zomzimba kwaye ilahlekise nayiphi na inzuzo yonyango inokuvuna.
Xa kuthethwa oko, kugxininiso oluninzi lubekwe kwi-inoculation ngqo ye-BNAbs kubantu abanokusuleleka koGawulayo. Enye ye-BNAb, eyaziwa njenge-3BNC117, ayibonakali nje ukuvimba ukusulelwa kwintsholongwane elitsha kodwa ukususa iiseli ezinegciwane le-HIV ngokunjalo. Indlela enjalo ingenza olunye usuku luvumeleke enye indlela okanye indlela yokongezelela unyango kubantu abasele benentsholongwane.
Ukugcina okanye ukubuyisela ukuthembeka kwe-Immune
Nangona izazinzulu zakwazi ukwenza ngokukodwa ukuveliswa kwe-bnAbs, kunokufuna impendulo enamandla yomzimba. Oku kubhekwa ngumngeni omkhulu njengoko i-HIV ngokwayo ibangela ukunyanzelwa kwe-immune ngokubulala ngokuzenzekelayo "i-CD" T-cell "
Ukongezelela, amandla omzimba wokulwa ne-HIV kunye nokuthiwa "umbulali" i-CD8 T-cell ihamba ngokuthe ngcembe ngexesha elide njengoko umzimba uphantsi kwinto eyaziwa ngokuba yintlungu yomzimba . Ngexesha lokusuleleka kwintsholongwane engapheliyo, isimiso somzimba sokuzivikela sisisoloko silawulwa ngokwawo ukuqinisekisa ukuba ayikugqithisekanga (kubangele isifo esisisigxina) okanye singagxininiswanga (ukuvumela ukuba amagciwane aqhubeke angapheliyo).
Ingakumbi ngexesha lokusuleleka kwexesha elide le-HIV, ukusetyenziswa kwangaphantsi kunokubangela ukuba i-CD4 iiseli zisuswe ngokukhawuleza kwaye umzimba ungakwazi ukufumanisa i-pathogen (imeko efana neyogulane nomhlaza). Xa kwenzeka oko, isistim somzimba sokuzivikela sisichaza "sibeka iibhuleki" kwimpendulo efanelekileyo, okwenza kube ngaphantsi kunako ukukwazi ukuzimela.
Izazinzulu kwiYunivesithi yase-Emory sele iqalile ukuhlola ukusetyenziswa kwamagciwane anqamlekileyo okuthiwa i- ipilimumab , enokukwazi "ukukhulula iibhuleki" kunye nokuvuselela ukuveliswa kweeseli ze-CD8.
Enye yezinto ezifunyenwe ngokuphangaleleyo zophando, okwangoku kwizilingo zokubamba, zibandakanya ukusetyenziswa kwabasebenzi abakhubazekile "igobolondo" yegciwane lesifo se-herpes esibizwa ngokuba yi-CMV apho kufakwe ingqungquthela engabangela izifo ze-SIV (i-primate version ye-HIV) . Xa izifundo zifakwe kwi-CMV, i-body yaphendula "ukuhleka" kwentsholongwane ngokukhawuleza ukuvelisa i-CD8 T-cell cell ukulwa noko bakukholelwayo ukuba bakholelwa ukuba yi-SIV.
Yintoni eyenza imodeli ye-CMV ngokunyanzelisayo ukuba i-virus ye-herpes ayigxothwanga emzimbeni, njengengcinezelo ebandayo, kodwa igcina iphinda iphinde icacise. Ingaba oku kunika ukukhuseleka kwexesha elide akukafuneka kuqinisekiswe, kodwa kunika ubungqina obunyanzelisayo.
Ukucoca nokubulala i-HIV yangokugqibela
Enye yemingcipheko enkulu ekuphuhliseni i-HIV yokugonya yijubane apho intsholongwane iyakwazi ukumisela iindawo zokugcina ukukhusela i-immune. Kukholelwa ukuba oku kuya kwenzeka ngokukhawuleza nje ngeeyure ezine xa kuthengiswa ngesondo ngomlomo-ngokukhawuleza kusuka kwindawo yesifo kwi-lymph nodes-ukuya kutsho kweentsuku ezine kwezinye iintlobo zesistim sokulala okanye ngokwesini .
Okwangoku, asinakuqinisekiswa ngokupheleleyo nangona indlela eninzi okanye enkulu ngayo le mijelo ingabikho okanye iyakwazi ukuvelisa isaphulelo se-viral (oko kukuthi, ukubuyela kwintsholongwane) kulabo bakholwa ukuba banokusulelwa isifo.
Ezinye zeengqungquthela zophando namhlanje zibandakanya icebo elibizwa ngokuba yi- "kick-kill" iqhinga ngokusebenzisa ama-agent avuselelayo "anokukhaba" i-HIV engavaliyo ekufihliweyo, ngaloo ndlela avumela i-arhente yesibini okanye isicwangciso "sokubulala" intsholongwane entsha.
Ngaloo nto, izazinzulu ziye zaphumelela ngokusebenzisa iziyobisi ezibizwa ngokuba yi-HDAC inhibitors, eziye zenziwa ngokuqhelekileyo ekuphatheni izifo zesifo sokuxhamla kunye nesimo sengqondo. Nangona uphando luboniswe ukuba izidakamizwa ezintsha ze-HDAC ziyakwazi "ukuvusa" intsholongwane engapheliyo, akukho namnye akwazi ukucima iindawo zokuhlala okanye ukunciphisa ubukhulu bawo. Amathemba athatyathwa ngokusetyenziswa okuhlangeneyo kwe-HDAC kunye nezinye i- adjethi zamachiza eziveli (zibandakanya i- PEP005 , esetyenziselwa ukuphatha uhlobo lomhlaza womhlaza wesikhumba).
Ingxaki eninzi, nangona kunjalo, kukuba i-HDAC inhibitors inokubangela ubuthi kunye nokunciphisa iimpendulo zomzimba. Ngenxa yoko, izazinzulu zikhangele eklasini yezilwanyana, ezibizwa ngokuba yi-TLA agonists, ezibonakala zikwazi ukuvuselela iimpendulo zokuzivikela komzimba kunokuba "zithintele" intsholongwane ngaphandle kokufihla. Izifundo zokuqala ze-primate ziye zithembisa, kungekhona nje ukunciphisa ukulinganiswa kweendawo zokugcina ezikhoyo kodwa ukunyuka okukhulu kwi-CD8 "yokubulala" isebenzi yeseli.
> Imithombo:
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