Uphando lubonisa ukuba ukuthomalalisa izilwa-buhlungu ezibangelwa kugonyo kunokukhusela izilwanyana kusulelo lwe-HIV.
Ukuphuhlisa iHIV ekhuselekileyo nesebenzayo (Human Immunodeficiency Virus) lokugonya, nangona ukuya kwi-30 izilingo zeklinikhi eziqhubekayo, ngumngeni ojongene noluntu lophando amashumi eminyaka. Le yimeko ngaphandle kokwenza inkqubela entle kukuqonda ukuba intsholongwane kagawulayo idibana njani namajoni omzimba. Omnye wemingeni engundoqo kule ndawo kukukwazi HIV ukuphindaphinda ngokukhawuleza kunye nokwakheka kwemfuzo okutshintshwe kancinane ngalo lonke ixesha. Ukungathathi hlangothi maqhinga eziveliswa ngokuchasene ne-HIV zibonwa zingonelanga ukucima ngokupheleleyo HIV usulelo ngenxa yokuba abanakuze banikeze ukhuseleko kwiintlobo ezahlukeneyo ze HIV. Kodwa nalapho, izilwa-buhlungu ze-HIV ezibangelwa sisitofu zisaza kubaluleka ekukhuseleni koku usulelo.
Iingozi zosulelo lwe-HIV
Ngelishwa, eyona njongo iphambili ye-HIV intsholongwane sisixokelelwano sethu sokhuselo lomzimba esimele ukusikhusela kwasekuqaleni. Lo ngowona mceli mngeni mkhulu ekujonganeni ne HIV usulelo. Omnye umda kuphando kwi HIV isitofu sesokuba asinakuvavanywa elabhoratri kwimizekelo yezilwanyana njengeempuku kuba HIV yosulela abantu kuphela. Olunye uphando luqhutywe kwiprimate elingana ne-HIV ebizwa ngokuba yi-SIV kodwa le iseyimodeli engafezekanga.
Oosonzululwazi baphinde bazama ukwenza iimpuku ze-bi-paternal (iimpuku ezinootata ababini), kodwa ukusebenzisa i-DNA eyindoda kwaba ngumngeni omkhulu njengoko kwakubandakanya ukulungiswa kwe-haploid ESCs equlethe i-DNA yomzali oyindoda kwaye kwafuneka kucinywe imimandla esixhenxe yemfuzo. Ezi seli zaye zatofwa kunye nedlozi lenye impuku eyindoda kwiseli yeqanda lomfazi apho i-nucleus equlethe imathiriyeli yemfuzo yobufazi yasuswa. Iimbumba ezidalwe ngoku zine-DNA kuphela evela kwindoda eyathi yatshintshelwa ecaleni kwe-placenta kumama abambeleyo abaye bawathwala kude kube lixesha elipheleleyo. Nangona kunjalo, ayizange isebenze kakuhle kwiimpuku zexesha elipheleleyo ezili-12 (i-2.5 yepesenti yazo zonke) ezizalwe ngootata ababini njengoko zasinda kuphela iiyure ze-48.
Isitofu esitsha sokugonya i-HIV
Isitofu sokugonya sokulinga i-HIV esiyilwe ngabaphandi be-Scripps Institute USA sibonwa sisebenza kwiiprimates ezingengabo abantu - i-rhesus monkeys. Injongo yayikukukwazi ukwenza izilwa-buhlungu ezithomalalisa umzimba ezinokuthi zenziwe ngogonyo kwaye ezi zilwa-buhlungu zaziza 'kufundisa' amajoni omzimba ukulwa intsholongwane kaGawulayo ngokujolisa kwindawo esemngciphekweni kwintsholongwane. Isitshixo kwimpendulo eyomeleleyo ye-immune kunye naluphi na ugonyo kukukhetha i-antigen efanelekileyo (apha, HIV okanye inxalenye yayo) enokuvuselela amajoni omzimba ukuba enze impendulo efunekayo. Uphando lubonise ukuba izilwa-buhlungu ezilolo hlobo kufuneka zibophelele kwi-protein trimer yangaphandle yentsholongwane kwaye ukuba oku kuyenzeka izilwa-buhlungu zinokukhusela umzimba ngempumelelo ekuhlaselweni yintsholongwane. Owona mceli mngeni mkhulu apha kukuba izinto eziphilayo mazikwazi ukuzenzela ezi zilwa-buhlungu ngokwazo. Oku kunokufezekiswa kuphela xa amajoni omzimba evezwe kwiprotein trimer yangaphandle yentsholongwane, ngaloo ndlela ufumana uqeqesho ukuze akwazi ukuchonga into ekujoliswe kuyo kwaye avelise izilwa-buhlungu ezichanekileyo ezichasene nayo.
Iprotein trimer yabonwa ingazinzanga kakhulu xa ibekwe yodwa kwaye abaphandi abakwazanga ukuyibeka yodwa ngaphandle kokuphuka. Ngo-2013, oosonzululwazi bakwazile ukwenza injineli ngempumelelo yemfuzo itrima ezinzileyo ebizwa ngokuba yi-SOSIP eyayikhangeleka ifana kakhulu ne-HIV imvulophu trimer yeprotein. Kuphononongo lwangoku izazinzulu zisebenzise oku ukuyila umfuniselo HIV Isitofu sokugonya esinokuqulatha isilinganisi se-SOSIP esizinzileyo kwaye besifuna ukujonga ukuba oku kungavusa amajoni omzimba ukuba avelise izilwa-buhlungu ezifunekayo ukukhusela kusulelo lwe-HIV.
Isitofu sokugonya esiyiliweyo savavanywa kumaqela amabini eeprimate rhesus macaques engeyoyabantu. Kuphononongo lwangaphambili, iinkawu zibonwe ukuba ziphuhlisa amanqanaba asezantsi okanye aphezulu e-antibody emva kogonyo. Kuphononongo lwangoku, ezintandathu kwezi nkawu zakhethwa kwaye ezongezelelweyo ezilishumi elinesibini iiprimates ezingagonywanga zasetyenziswa njengolawulo. Iinkawu zazisesichengeni sohlobo lwentsholongwane ebizwa ngokuba yi-SHIV (inguqulelo eyenziwe ngokwemfuza ye-SIMian ye-HIV equlethe i-trimer efanayo nentsholongwane yomntu). Olu luhlobo lwentsholongwane olukwaziyo ukumelana nentsholongwane ebizwa ngokuba yintsholongwane ye-Tier 2 kuba kunzima ukuyiphelisa kwaye oko kungumngeni ngendlela efanayo neyentsholongwane yomntu kwaye olu hlobo luchaphazela abantu abaninzi.
Isitofu sokugonya esitsha senza ukuba iinkawu zenze izilwa-buhlungu ezingathinteliyo ngokuchasene nolu hlobo lwentsholongwane kwaye zisebenze kakuhle kwiinkawu ezazigonyelwe ngaphambili kunye namanqanaba aphezulu amajoni akhusela isilwanyana ngokuchasene nosulelo. Nangona kunjalo, isiphumo sibonisa ngokucacileyo ukuba impumelelo ifunyenwe kwiinkawu ezinamazinga aphezulu e-antibody athetha ukuba oku kuya kuba yinqobo yemiqathango. Kwakhona, ezi zilwanyana bezigonyiwe ngaphambili, amanqanaba azo e-antibody aqala ukuncipha kwiiveki okanye kwiinyanga ezilandela ugonyo. Kwaqokelelwa uqikelelo lokuba angakanani na amanqanaba e-antibody ayakudingeka ukugcina usulelo.
Olu phononongo lupapashwe kwi-Immunity lubonelela ngoqikelelo lokuqala lokuba angakanani na amanqanaba e-antibodies anokuthi afuneke ukukhusela umntu HIV. Kuyathakazelisa ukuqaphela ukuba kuphela imveliso ye-neutralize antibodies yi-immune system yabonwa njengento ebalulekileyo. Injongo iya kuba kukugcina amanqanaba aphezulu e-antibody. Kusekho ikhefu phambi kokuba esi sitofu sokugonya siye kulingo lwezonyango lwabantu. Ababhali baqinisekile ukuba oku kukuqonda okuphambili okuphunyeziweyo kwintsimi ye HIV isitofu sokugonya phantse emva kwamashumi amathathu eminyaka. Isicwangciso esinjalo sinokusetyenziswa kwezinye iintlobo ze HIV njengokuba.
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{Unokufunda iphepha lokuqala lophando ngokunqakraza ikhonkco le-DOI elinikwe ngezantsi kuluhlu lwemithombo ecatshulweyo (s)}
Umthombo (s)
UPauthner MG et al. 2018. UKhuseleko oluBanjelwe kuGonyo olusuka kwi-Homologous Tier 2 SHIV Challenge kwiNqanaba eziNgezoBuntu luxhomekeke kwiSerum-Neutralizing Antibody Titers. Ku khuselwa.
https://doi.org/10.1016/j.immuni.2018.11.011
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