HIV 1 Nef kaappaa T-imusolun immunologisen vasteen päävaihteen. säätelyn.

HIV 1 Nef indusoi trans-Golgi-verkostoon liittyneen Lck signaloinnin, mikä vaikuttaa immunologisen synapsin modulatiota firuksen replikaation eduksi. Samalla ihmisessä tauti pahenee. Viruksen Nef- tekijä saattaa epäkuntoon immunologisten synapsien järjestyneisyyden, mikä vallitsee T-imusolujen CD4+ ja antigeeniä esittävän(APC) B- lymfosyytin kesken, mikä koskeen TCR t-soluresetroin proksimaalista signalointia. Paradoksaalisesti Nef samlla lisää distaalista TCR- signalointia infektoituneissa T- CD4 + soluissa, minkä vaikutuksen katsotaan edistävän AIDS taudin patogeneesiä. ....... Blood. 2012 Jan 19;119(3):786-97. doi: 10.1182/blood-2011-08-373209. Epub 2011 Nov 28. HIV-1 Nef compensates for disorganization of the immunological synapse by inducing trans-Golgi network-associated Lck signaling. Pan X, Rudolph JM, Abraham L, Habermann A, Haller C, Krijnse-Locker J, Fackler OT. SourceDepartment of Infectious Diseases, Virology, University Hospital Heidelberg, Germany Abstract The Nef protein of HIV-1 facilitates viral replication and disease progression in vivo. Nef disturbs the organization of immunological synapses between infected CD4(+) T lymphocytes and antigen-presenting B-lymphocytes to interfere with TCR proximal signaling. Paradoxically, Nef enhances distal TCR signaling in infected CD4(+) T lymphocytes, an effect thought to be involved in its role in AIDS pathogenesis. ......´ Nef aiheuttaa -solurespetorin solunsisäistä aitioitumista ja täten muuntaa tämän TCR reseptorin vastetta antigeenistimulaatioon. ..... Using quantitative confocal microscopy and cell fractionation of Nef-expressing cells and HIV-1-infected primary human T lymphocytes, we found that Nef induces intracellular compartmentalization of TCR signaling to adjust TCR responses to antigenic stimulation...... Nef suuntaa poispäin plasmakalvosta toiselle reitille T-soluresptorin (TCR) signaloivan päävaihteen Lck kinaasiaktiivit altaat ja johtaa ne trans-Golgiverkostoon (TGN) . Täten estyy aktiivien Lck -tekijöiden rekrytointi immunologisiin synapseihin TCR:n jo puututtua asiaan ja niin signaalin alkuunpano plasmakalvossa rajoittuu. Nef reroutes kinase-active pools of the TCR signaling master switch Lck away from the plasma membrane (PM) to the trans-Golgi network (TGN), thereby preventing the recruitment of active Lck to the immunological synapse after TCR engagement and limiting signal initiation at the PM. ..... Mutta sensijaan Nef triggeröi trans-golgin verkostoon (TGN) liittyvän Ras- Erk- signaloinnin Lck:sta riippuvan aktivaation , mikä jää nyt edistämään T-imusolujen elossapysymistekijää IL- 2 ja näin lisäämään viruksen leviämistä ( immunologisesti epätarkoiksi tehdyissä) T- imusoluissa. ..... Instead, Nef triggers Lck-dependent activation of TGN-associated Ras-Erk signaling to promote the production of the T lymphocyte survival factor IL-2 and to enhance virus spread. ..... Jos saadaan aikaan Lck plasmamembraanikuljettajan Unc119 yliexpressio, palautuu Nef tekijän aiheuttamat väärentymät Lck- kulkeutumisissa ja T-solureseptorin signaloinnissa. Overexpression of the Lck PM transporter Unc119 restores Nef-induced subversions of Lck trafficking and TCR signaling...... Siis: HIV 1- viruksen N ef- tekijä kaappaa Lck-tekijän ( päävaihteen) sorteerauksen aktivoimalla selektiivisesti trans-golgin verkostoon(TGN) liittyvät puolet aitioituneen T- imusolureseptorin (TCR) signalointifunktiosta.Räätälöimällä kokoon T-imusolun antigeenistimulaatiolle antamia vasteita Nef optimoi miljöön HIV- 1 virukwsen replikoitumisen eduksi. .....Nef therefore hijacks Lck sorting to selectively activate TGN-associated arms of compartmentalized TCR signaling. By tailoring T-lymphocyte responses to antigenic stimulation, Nef optimizes the environment for HIV-1 replication.

Miten HIV muuntaa endoplasmisen verkoston ja Golgin laitteen funktion?

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