{"id":53895,"date":"2020-04-15T02:35:09","date_gmt":"2020-04-15T01:35:09","guid":{"rendered":"https:\/\/fjala.info\/?p=53895"},"modified":"2020-04-15T09:10:01","modified_gmt":"2020-04-15T08:10:01","slug":"sars-cov-2-infekton-limfocitet-t-permes-shkrirjes-se-saj-membranore-te-ndermjetesuar-nga-proteina","status":"publish","type":"post","link":"https:\/\/jehonashqiptare.al\/fjala\/sars-cov-2-infekton-limfocitet-t-permes-shkrirjes-se-saj-membranore-te-ndermjetesuar-nga-proteina\/","title":{"rendered":"SARS-CoV-2 infekton limfocitet T, p\u00ebrmes shkrirjes s\u00eb saj membranore t\u00eb nd\u00ebrmjet\u00ebsuar nga proteina"},"content":{"rendered":"

Nature.com<\/a><\/strong>, 7 prill 2020<\/em> – P\u00ebrktheu Arben \u00c7okaj<\/strong><\/em><\/span><\/p>\n

Xinling Wang<\/a>, Wei Xu<\/a>,\u00a0Gaowei Hu<\/a>, Shuai Xia<\/a>, Zhiping Sun<\/a>, Zezhong Liu<\/a>, Youhua Xie<\/a>, Rong Zhang<\/a>, Shibo Jiang<\/a> &\u00a0Lu Lu<\/a><\/p>\n

Cellular & Molecular Immunology<\/i><\/a>\u00a0(2020<\/span>) Citoje k\u00ebt\u00eb artikull<\/a><\/p>\n

COVID-19, s\u00ebmundja e re e koronavirus e shkaktuar nga SARS-CoV-2 dhe q\u00eb shp\u00ebrtheu n\u00eb fund t\u00eb vitit 2019 n\u00eb Wuhan, Kin\u00eb1<\/sup> u b\u00eb nj\u00eb pandemi n\u00eb mbar\u00eb bot\u00ebn. SARS-CoV-2 i p\u00ebrket gjinis\u00eb t\u00eb betacoronavirus dhe ka identitet 79.5% ndaj SARS-CoV. SARS-CoV-2 p\u00ebrdor enzim\u00ebn konvertuese t\u00eb angiotenzin\u00ebs 2 (ACE-2) si receptorin e saj t\u00eb hyrjes te prit\u00ebsi2<\/sup>.<\/p>\n

Manifestimet klinike t\u00eb COVID-19 p\u00ebrfshijn\u00eb pneumoni, diarre, dispne (v\u00ebshtir\u00ebsi n\u00eb frym\u00ebmarrje) dhe d\u00ebshtim t\u00eb shum\u00ebfisht\u00eb t\u00eb organeve. \u00cbsht\u00eb interesante se, limfocitopenia, si nj\u00eb tregues diagnostik, \u00ebsht\u00eb e zakonshme n\u00eb pacient\u00ebt me COVID-19. Xiong et al<\/em>. gjeti nj\u00eb rregullim t\u00eb rrug\u00ebve t\u00eb apoptoz\u00ebs, autofagis\u00eb dhe p53 n\u00eb PBMC t\u00eb pacient\u00ebve me COVID-193<\/sup>. Disa studime raportuan se limfocitopenia mund t\u00eb jet\u00eb e lidhur me vdekshm\u00ebrin\u00eb, ve\u00e7an\u00ebrisht n\u00eb pacient\u00ebt me nivele t\u00eb ul\u00ebta t\u00eb limfociteve T4<\/sup>,5<\/sup> CD3+<\/sup>, CD4+<\/sup> dhe CD8+<\/sup>. Lymfocitopenia u gjet edhe n\u00eb rastet e sindrom\u00ebs s\u00eb frym\u00ebmarrjes n\u00eb Lindjen e Mesme (MERS). MERS-CoV mund t\u00eb infektoj\u00eb drejtp\u00ebrdrejt limfocitet T primare njer\u00ebzore dhe t\u00eb shkaktoj\u00eb apoptoz\u00eb t\u00eb qeliz\u00ebs T p\u00ebrmes rrug\u00ebve apoptoze ekstrinike dhe intrinsike, por nuk mund t\u00eb kopjohet te limfocitet T6<\/sup>. Sidoqoft\u00eb, \u00ebsht\u00eb e paqart\u00eb n\u00ebse SARS-CoV-2 mund t\u00eb infektoj\u00eb edhe qelizat T, duke rezultuar n\u00eb limfocitopeni.<\/p>\n

P\u00ebr t\u00eb adresuar k\u00ebt\u00eb pyetje, ne vler\u00ebsuam ndjeshm\u00ebrin\u00eb e limfociteve T ndaj infeksionit SARS-CoV-2. P\u00ebr ta realizuar k\u00ebt\u00eb, SARS-CoV dhe SARS-CoV-2 t\u00eb pseudotipizuara u paketuan bazuar n\u00eb metodat e p\u00ebrshkruara m\u00eb par\u00eb.7<\/sup> Pseudoviruset mund t\u00eb infektonin qelizat lejuese (qelizat 293T \/ ACE2 dhe Huh7) duke shprehur receptorin ACE2, por nuk mund t\u00eb infektonin qelizat jo-pezmuese (qelizat HeLa) (Fig. 1a). Ne p\u00ebrdor\u00ebm pseudovirus me infektivitet t\u00eb barabart\u00eb me qelizat 293T \/ ACE2 (Fig. 1c) p\u00ebr t\u00eb infektuar dy linja qelizash limfocitare T, MT-2 dhe A3.01, me nj\u00eb nivel shum\u00eb t\u00eb ul\u00ebt, ose af\u00ebr nivelit t\u00eb shprehur t\u00eb mRNA t\u00eb hACE2 (Fig. 1b ). \u00c7udit\u00ebrisht, mbi disa p\u00ebrs\u00ebritje, ne pam\u00eb se linjat e qelizave T ishin duksh\u00ebm m\u00eb t\u00eb ndjeshme ndaj infeksionit SARS-CoV-2, kur u krahasuan me SARS-CoV (Fig. 1c).<\/p>\n

Me fjal\u00eb t\u00eb tjera, k\u00ebto rezultate na tregojn\u00eb se limfocitet T mund t\u00eb jen\u00eb m\u00eb lejuese ndaj infeksionit SARS-CoV-2 dhe m\u00eb pak lejues p\u00ebr infeksionin SARS-CoV, t\u00eb ngjashme me gjetjet n\u00eb nj\u00eb studim t\u00eb m\u00ebparsh\u00ebm.6<\/sup> Prandaj, \u00ebsht\u00eb e pranueshme, q\u00eb proteina S e SARS-CoV-2 mund t\u00eb nd\u00ebrmjet\u00ebsoj\u00eb infektivitetin e fuqish\u00ebm, madje edhe n\u00eb qelizat q\u00eb shprehin hACE2 t\u00eb ul\u00ebt, gj\u00eb q\u00eb, nga ana tjet\u00ebr, do t\u00eb shpjegoj\u00eb pse shkalla e transmetimit t\u00eb SARS-CoV-2 \u00ebsht\u00eb kaq e lart\u00eb. \u00cbsht\u00eb gjithashtu e mundur, q\u00eb receptor\u00ebt e tjer\u00eb t\u00eb nd\u00ebrmjet\u00ebsojn\u00eb hyrjen e SARS-CoV-2 n\u00eb qelizat T, si\u00e7 \u00ebsht\u00eb CD147, t\u00eb pranish\u00ebm n\u00eb sip\u00ebrfaqen e limfociteve T8<\/sup>, i cili koh\u00ebt e fundit u raportua se ishte nj\u00eb rrug\u00eb e re pushtuese p\u00ebr SARS-CoV-2.9<\/sup><\/p>\n

\"\"<\/a>Fig. 1<\/strong>
\nNga: SARS-CoV-2 infekton limfocitet T, p\u00ebrmes shkrirjes s\u00eb saj membranore t\u00eb nd\u00ebrmjet\u00ebsuar nga proteina.<\/em><\/span><\/p>\n

Ndjeshm\u00ebria e limfociteve T ndaj infeksionit SARS-CoV-2<\/strong>.
\na<\/strong>. infeksion i pseudotipizuar SARS-CoV-2 dhe SARS-CoV. 293T \/ ACE2 dhe Huh7 jan\u00eb qeliza lejuese, nd\u00ebrsa HeLa \u00ebsht\u00eb nj\u00eb linj\u00eb qelizore jopermeruese.
\nb<\/strong>. Shprehja e ACE2 mRNA n\u00eb qelizat T. Qelizat 293T \/ ACE2 t\u00eb p\u00ebrdorura si nj\u00eb kontroll.
\nc<\/strong>. Infeksioni i pseudotipizuar SARS-CoV-2 dhe SARS-CoV n\u00eb linjat qelizore limfoide T.
\nd<\/strong>. Pengimi i peptidit EK1 n\u00eb pseudotipet SARS-CoV-2 n\u00eb qelizat MT-2.
\ne<\/strong>. Shkrirja e S-qeliza-qeliza-nd\u00ebrmjet\u00ebsuar nga SARS-CoV-2 n\u00eb qelizat MT-2. Qelizat MT-2 u kokultur\u00ebn me qelizat 293T \/ SARS-CoV-2 \/ EGFP. Bashkimi qeliz\u00eb-qeliz\u00eb u fotografua n\u00ebn nj\u00eb mikroskop optik me fluoreshenc\u00eb ose drit\u00eb t\u00eb dukshme. Qelizat e shkrira tregohen me nj\u00eb shigjet\u00eb t\u00eb bardh\u00eb. Shiriti mee shkall\u00ebsh 800 \u03bcm.
\nf<\/strong>. Zbulimi i qelizave SARS-CoV-2 NP-pozitive me citometri t\u00eb rrjedh\u00ebs. Qelizat MT-2 u infektuan me SARS-CoV-2 n\u00eb 1TCID50 p\u00ebr qeliz\u00eb, p\u00ebrkat\u00ebsisht. Qelizat u fiksuan dhe u permeabilizuan n\u00eb 24 dhe 48 or\u00eb pas infeksionit dhe imunoloheshin p\u00ebr zbulimin e SARS-CoV-2 NP.
\ng<\/strong>. Infeksioni i qelizave MT-2 nga SARS-CoV-2 \u00ebsht\u00eb abortiv. Qelizat u inokuluan me SARS-CoV-2 n\u00eb 1TCID50 p\u00ebr qeliz\u00eb dhe u kultivuan n\u00eb 1, 6, 24 dhe 48 or\u00eb pas infeksionit.Lizat e qelizave (lart) dhe pluskues (m\u00eb posht\u00eb) u mblodh\u00ebn p\u00ebr t\u00eb zbuluar gjenin viral N me RT-qPCR. N\u00eb panele, shirita dhe shiritat e gabimit p\u00ebrfaq\u00ebsohen mjetet dhe devijimet standarde. Analizat statistikore jan\u00eb kryer duke p\u00ebrdorur testin t t\u00eb pa-bashkuar. *p < 0.05<\/em><\/p>\n

\n

P\u00ebr t\u00eb vler\u00ebsuar n\u00ebse SARS-CoV-2 hyn n\u00eb limfocitet T, p\u00ebrmes endocitoz\u00ebs pa nd\u00ebrmjet\u00ebsues, ne kemi p\u00ebrdorur peptidin EK1, i cili ka treguar se frenon protein\u00ebn spike t\u00eb SARS-CoV-2 (S), me nd\u00ebrmjet\u00ebsim qeliz-qeliz\u00eb dhe infeksion pseudovirus7<\/sup>,10<\/sup>. N\u00eb m\u00ebnyr\u00eb t\u00eb ve\u00e7ant\u00eb, ajo pengon infeksionin e nd\u00ebrmjet\u00ebsuar nga receptori duke bashk\u00ebvepruar me HR1 p\u00ebr t\u00eb bllokuar formimin e tuf\u00ebs me gjasht\u00eb helika (6-HB), duke penguar m\u00eb tej bashkimin midis membranave virale dhe qelizave t\u00eb synuara. Ne zbuluam se peptidi EK1 kishte aktivitet t\u00eb r\u00ebnd\u00ebsish\u00ebm frenues ndaj pseudoviruseve SARS-CoV-2 n\u00eb qelizat MT-2 (Fig. 1d), duke sugjeruar q\u00eb hyrja e virusit varet nga shkrirja e nd\u00ebrmjet\u00ebsuar nga receptori. Sidoqoft\u00eb, vet\u00ebm nj\u00eb p\u00ebrqendrim i lart\u00eb (40 \u03bcM) i EK1 kishte aktivitet frenues n\u00eb qelizat MT-2. Nd\u00ebrkoh\u00eb, vlera IC50 e EK1 ishte 2.38 \u03bcM n\u00eb qelizat 293T \/ ACE-210<\/sup>.<\/p>\n

K\u00ebto rezultate sugjerojn\u00eb q\u00eb SARS-CoV-2 gjithashtu mund t\u00eb hyj\u00eb n\u00eb limfocitet T p\u00ebrmes rrug\u00ebs endocitoze t\u00eb nd\u00ebrmjet\u00ebsuar nga receptori. P\u00ebr ta sqaruar k\u00ebt\u00eb, ne kemi kryer nj\u00eb analiz\u00eb t\u00eb bashkimit qeliz\u00eb-qeliz\u00eb t\u00eb nd\u00ebrmjet\u00ebsuar nga SARS-CoV-S sipas studimeve t\u00eb m\u00ebparshme7<\/sup>,10<\/sup>. Pas 48 h t\u00eb kultur\u00ebs, qelizat 293T shprehin protein\u00ebn SARS-CoV-2 S t\u00eb shkrir\u00eb me qelizat MT-2. Krahasuar me qelizat e pashfryt\u00ebzuara, qelizat e bashkuara grumbullohen s\u00eb bashku dhe shfaqen si nj\u00eb mas\u00eb e madhe e gjelb\u00ebr e zbeht\u00eb fluoreshente. N\u00eb t\u00eb kund\u00ebrt, asnj\u00eb qeliz\u00eb e shkrir\u00eb nuk u gjet n\u00eb koktur\u00ebn SARS-CoV (Fig. 1e). Prandaj, mund t\u00eb konkludohet se SARS-CoV-2 mund t\u00eb infektoj\u00eb qelizat T, p\u00ebrmes shkrirjes s\u00eb membran\u00ebs s\u00eb nd\u00ebrmjet\u00ebsuar nga proteina S.<\/p>\n

P\u00ebr ta p\u00ebrcaktuar m\u00eb tej ndjeshm\u00ebrin\u00eb e qelizave MT-2 ndaj virusit t\u00eb gjall\u00eb, ne kemi p\u00ebrdorur SARS-CoV-2 p\u00ebr t\u00eb infektuar qelizat MT-2 dhe zbuluam nukleoprotein\u00ebn SARS-CoV-2 (NP) n\u00eb qeliza, si\u00e7 \u00ebsht\u00eb raportuar m\u00eb par\u00eb.6<\/sup> N\u00eb m\u00ebnyr\u00eb t\u00eb ve\u00e7ant\u00eb, disa qeliza MT-2 u infektuan me SARS-CoV-2 (Fig. 1f). N\u00eb m\u00ebnyr\u00eb sasiore, p\u00ebrqindja e qelizave t\u00eb SARS-CoV-2 NP-pozitive MT-2 ishte 23.11% m\u00eb e lart\u00eb se ajo e qelizave t\u00eb pa infektuara n\u00eb 24 or\u00eb pas infeksionit, q\u00eb \u00ebsht\u00eb rreth 4.6-fish i pjes\u00ebs n\u00eb 1 or\u00eb (Fig. 1f). Ky rezultat do t\u00eb thot\u00eb q\u00eb virusi dep\u00ebrtoi n\u00eb qelizat MT-2 n\u00eb 24 or\u00eb dhe i infektoi ato.<\/p>\n

Duke pasur parasysh q\u00eb MERS-CoV mund t\u00eb infektoj\u00eb n\u00eb m\u00ebnyr\u00eb efikase, por jo t\u00eb p\u00ebrs\u00ebritur, n\u00eb limfocitet T,6<\/sup> ne zbuluam m\u00eb tej numrin e kopjeve t\u00eb gjenomit viral n\u00eb pika t\u00eb ndryshme kohore pas infeksionit p\u00ebr t\u00eb eksploruar karakteristikat e p\u00ebrs\u00ebritjes s\u00eb SARS-CoV-2 n\u00eb qelizat MT-2. Ngjash\u00ebm me MERS-CoV, SARS-CoV-2 nuk arriti t\u00eb p\u00ebrs\u00ebritet n\u00eb qelizat MT-2 (Fig. 1g). Numri i kopjeve t\u00eb gjenomit viral n\u00eb 6 or\u00eb ishte duksh\u00ebm m\u00eb i lart\u00eb se sa pikat e tjera kohore n\u00eb lizatin qelizor, por gjithnj\u00eb mbeti i q\u00ebndruesh\u00ebm n\u00eb t\u00eb gjitha pikat e koh\u00ebs n\u00eb supernatant\u00eb. K\u00ebto rezultate sugjerojn\u00eb q\u00eb SARS-CoV-2 mund t\u00eb hyj\u00eb n\u00eb qelizat MT-2 n\u00eb infeksionin pas 6 or\u00ebsh, por nuk p\u00ebrs\u00ebritet, dhe m\u00eb pas degradohet ARN-ja virale. N\u00eb supernatant\u00eb, kopjet virale t\u00eb zbuluara mund t\u00eb jen\u00eb sfondi i virioneve t\u00eb mbetura, t\u00eb ngjashme me rezultatet e studimit t\u00eb m\u00ebparsh\u00ebm MERS-CoV (Fig. 1g).6<\/sup><\/p>\n

Bazuar n\u00eb rezultatet e pseudovirusit dhe infeksionit t\u00eb virusit t\u00eb gjall\u00eb, k\u00ebtu kemi v\u00ebrtetuar se (1) SARS-CoV-2 mund t\u00eb infektoj\u00eb qelizat T, (2) qelizat T t\u00eb infektuara nga SARS-CoV-2 p\u00ebrmes qelizave T t\u00eb infektuara nga receptori, S, me nd\u00ebrmjet\u00ebsim t\u00eb proteinave, dhe (3) infeksioni mund t\u00eb pengohet nga peptidi EK1. Sidoqoft\u00eb, kemi v\u00ebrejtur nj\u00eb nivel shum\u00eb t\u00eb ul\u00ebt t\u00eb shprehjes s\u00eb hACE2 n\u00eb qelizat T; Prandaj, ne propozuam m\u00eb tej, q\u00eb nj\u00eb receptor i ri t\u00eb nd\u00ebrmjet\u00ebsonte hyrjen SARS-CoV-2 n\u00eb qelizat T. Ngjash\u00ebm me MERS-CoV, infeksioni i SARS-CoV-2 i qelizave T \u00ebsht\u00eb abortiv. Nj\u00eb studim i fundit raportoi se leximet virale mezi shfaqen n\u00eb mostrat PBMC nga pacient\u00ebt COVID-19 p\u00ebrmes sekuencave transkriptome t\u00eb ARN-ve. K\u00ebshtu, \u00ebsht\u00eb konstatuar se SARS-CoV-2 nuk mund t\u00eb infektoj\u00eb PBMC. Sidoqoft\u00eb, karakteristikat transkriptomike t\u00eb PBMC, u zbuluan dhe u analizuan nga tre pacient\u00eb. Dy lexime SARS-CoV-2 u zbuluan n\u00eb PBMC t\u00eb nj\u00eb pacienti, dhe zero lexime n\u00eb nj\u00eb tjet\u00ebr.3<\/sup><\/p>\n

Ky rezultat mund t’i atribuohet replikimit joproduktiv t\u00eb SARS-CoV-2 n\u00eb limfocitet T, me gjenom t\u00eb vog\u00ebl viral n\u00eb PBMCs ndoshta degraduese n\u00eb most\u00ebr, procesi i mbledhjes dhe nxjerrjes s\u00eb ARN-s\u00eb. K\u00ebshtu q\u00eb, pyetjet e infeksionit SARS-CoV-2 dhe replikimit n\u00eb qelizat T primare dhe n\u00ebse infeksioni shkakton apoptoz\u00eb n\u00eb qelizat T ende kan\u00eb nevoj\u00eb p\u00ebr hulumtime t\u00eb m\u00ebtejshme, duke evokuar potencialisht ide t\u00eb reja n\u00eb lidhje me mekanizmat patogjen\u00eb dhe nd\u00ebrhyrjet terapeutike.<\/p>\n

\n

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\nXia, S. et al. Inhibicioni i infeksionit SARS-CoV-2 (m\u00eb par\u00eb 2019-nCoV) nga nj\u00eb frenues shum\u00eb i fuqish\u00ebm i bashkimit pan-koronavirus, duke synuar protein\u00ebn e tij pikante, q\u00eb p\u00ebrmban nj\u00eb kapacitet t\u00eb lart\u00eb, p\u00ebr t\u00eb nd\u00ebrmjet\u00ebsuar shkrirjen e membran\u00ebs. Res Res. https:\/\/doi.org\/10.1038\/s41422-020-0305-x<\/a> (2020).<\/p>\n","protected":false},"excerpt":{"rendered":"

Nature.com, 7 prill 2020 – P\u00ebrktheu Arben \u00c7okaj Xinling Wang, Wei Xu,\u00a0Gaowei Hu, Shuai Xia, Zhiping Sun, Zezhong Liu, Youhua Xie, Rong Zhang, Shibo Jiang &\u00a0Lu Lu Cellular & Molecular Immunology\u00a0(2020) Citoje k\u00ebt\u00eb artikull COVID-19, s\u00ebmundja e re e koronavirus e shkaktuar nga SARS-CoV-2 dhe q\u00eb shp\u00ebrtheu n\u00eb fund t\u00eb vitit 2019 n\u00eb Wuhan, Kin\u00eb1 […]<\/p>\n","protected":false},"author":1,"featured_media":53849,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[2,173],"tags":[],"class_list":["post-53895","post","type-post","status-publish","format-standard","has-post-thumbnail","category-artikuj","category-covid-19"],"yoast_head":"\nSARS-CoV-2 infekton limfocitet T, p\u00ebrmes shkrirjes s\u00eb saj membranore t\u00eb nd\u00ebrmjet\u00ebsuar nga proteina - FJALA e LIR\u00cb<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/jehonashqiptare.al\/fjala\/sars-cov-2-infekton-limfocitet-t-permes-shkrirjes-se-saj-membranore-te-ndermjetesuar-nga-proteina\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"SARS-CoV-2 infekton limfocitet T, p\u00ebrmes shkrirjes s\u00eb saj membranore t\u00eb nd\u00ebrmjet\u00ebsuar nga proteina - 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