HIV infection drives interferon signaling within intestinal SARS-CoV-2 target cells.
HIV infection drives interferon signaling within intestinal SARS-CoV-2 target cells.
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DOI：
10.1172/jci.insight.148920
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发表时间：
2021-08-23
期刊：
影响因子：
8
通讯作者：
Kløverpris HN
中科院分区：
文献类型：
--
作者：
Fardoos R;Asowata OE;Herbert N;Nyquist SK;Zungu Y;Singh A;Ngoepe A;Mbano IM;Mthabela N;Ramjit D;Karim F;Kuhn W;Madela FG;Manzini VT;Anderson F;Berger B;Pers TH;Shalek AK;Leslie A;Kløverpris HN
SARS-CoV-2感染人类胃肠道（GI）的上皮细胞并引起相关症状。HIV感染会损害肠道内稳态，并与COVID-19致死风险增加有关。为了研究这些观察结果之间的潜在联系，我们分析了慢性HIV感染个体和未感染对照的淋巴和粘膜人体组织的单细胞转录谱和SARS-CoV-2进入受体表达。吸收性肠上皮细胞显示SARS-CoV-2受体ACE 2、TMPRSS 2和TMPRSS 4的最高共表达，其中ACE 2表达与典型干扰素应答和抗病毒基因相关。慢性治疗的HIV感染与肠道肠上皮细胞中明确的抗病毒应答相关，并且出乎意料地与ACE 2和TMPRSS 2靶细胞的大幅减少相关。然而，来自SARS-CoV-2感染个体的肠道组织在大肠和小肠（包括HIV共感染个体）中均显示出丰富的SARS-CoV-2核衣壳蛋白。因此，HIV感染者胃肠道中抗病毒应答基因的上调和ACE 2和TMPRSS 2的下调并不能阻止SARS-CoV-2在该区域的感染。这些HIV相关肠粘膜变化对SARS-CoV-2感染动力学、疾病严重程度和疫苗应答的影响尚不清楚，需要进一步研究。
SARS-CoV-2 infects epithelial cells of the human gastrointestinal (GI) tract and causes related symptoms. HIV infection impairs gut homeostasis and is associated with an increased risk of COVID-19 fatality. To investigate the potential link between these observations, we analyzed single-cell transcriptional profiles and SARS-CoV-2 entry receptor expression across lymphoid and mucosal human tissue from chronically HIV-infected individuals and uninfected controls. Absorptive gut enterocytes displayed the highest coexpression of SARS-CoV-2 receptors ACE2, TMPRSS2, and TMPRSS4, of which ACE2 expression was associated with canonical interferon response and antiviral genes. Chronic treated HIV infection was associated with a clear antiviral response in gut enterocytes and, unexpectedly, with a substantial reduction of ACE2 and TMPRSS2 target cells. Gut tissue from SARS-CoV-2–infected individuals, however, showed abundant SARS-CoV-2 nucleocapsid protein in both the large and small intestine, including an HIV-coinfected individual. Thus, upregulation of antiviral response genes and downregulation of ACE2 and TMPRSS2 in the GI tract of HIV-infected individuals does not prevent SARS-CoV-2 infection in this compartment. The impact of these HIV-associated intestinal mucosal changes on SARS-CoV-2 infection dynamics, disease severity, and vaccine responses remains unclear and requires further investigation.
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影响因子：
82.9
作者：
Muus, Christoph;Luecken, Malte D.;Eraslan, Gokcen;Sikkema, Lisa;Waghray, Avinash;Heimberg, Graham;Kobayashi, Yoshihiko;Vaishnav, Eeshit Dhaval;Subramanian, Ayshwarya;Smillie, Christopher;Jagadeesh, Karthik A.;Duong, Elizabeth Thu;Fiskin, Evgenij;Triglia, Elena Torlai;Ansari, Meshal;Cai, Peiwen;Lin, Brian;Buchanan, Justin;Chen, Sijia;Shu, Jian;Haber, Adam L.;Chung, Hattie;Montoro, Daniel T.;Adams, Taylor;Aliee, Hananeh;Allon, Samuel J.;Andrusivova, Zaneta;Angelidis, Ilias;Ashenberg, Orr;Bassler, Kevin;Becavin, Christophe;Benhar, Inbal;Bergenstrahle, Joseph;Bergenstrahle, Ludvig;Bolt, Liam;Braun, Emelie;Bui, Linh T.;Callori, Steven;Chaffin, Mark;Chichelnitskiy, Evgeny;Chiou, Joshua;Conlon, Thomas M.;Cuoco, Michael S.;Cuomo, Anna S. E.;Deprez, Marie;Duclos, Grant;Fine, Denise;Fischer, David S.;Ghazanfar, Shila;Gillich, Astrid;Giotti, Bruno;Gould, Joshua;Guo, Minzhe;Gutierrez, Austin J.;Habermann, Arun C.;Harvey, Tyler;He, Peng;Hou, Xiaomeng;Hu, Lijuan;Hu, Yan;Jaiswal, Alok;Ji, Lu;Jiang, Peiyong;Kapellos, Theodoros S.;Kuo, Christin S.;Larsson, Ludvig;Leney-Greene, Michael A.;Lim, Kyungtae;Litvinukova, Monika;Ludwig, Leif S.;Lukassen, Soeren;Luo, Wendy;Maatz, Henrike;Madissoon, Elo;Mamanova, Lira;Manakongtreecheep, Kasidet;Leroy, Sylvie;Mayr, Christoph H.;Mbano, Ian M.;McAdams, Alexi M.;Nabhan, Ahmad N.;Nyquist, Sarah K.;Penland, Lolita;Poirion, Olivier B.;Poli, Sergio;Qi, CanCan;Queen, Rachel;Reichart, Daniel;Rosas, Ivan;Schupp, Jonas C.;Shea, Conor, V;Shi, Xingyi;Sinha, Rahul;Sit, Rene, V;Slowikowski, Kamil;Slyper, Michal;Smith, Neal P.;Sountoulidis, Alex;Strunz, Maximilian;Sullivan, Travis B.;Sun, Dawei;Talavera-Lopez, Carlos;Tan, Peng;Tantivit, Jessica;Travaglini, Kyle J.;Tucker, Nathan R.;Vernon, Katherine A.;Wadsworth, Marc H.;Waldman, Julia;Wang, Xiuting;Xu, Ke;Yan, Wenjun;Zhao, William;Ziegler, Carly G. K.
通讯作者：
Ziegler, Carly G. K.
ACE2将氨基酸营养不良与微生物生态学和肠炎联系起来。
影响因子：
64.8
作者：
Hashimoto T;Perlot T;Rehman A;Trichereau J;Ishiguro H;Paolino M;Sigl V;Hanada T;Hanada R;Lipinski S;Wild B;Camargo SM;Singer D;Richter A;Kuba K;Fukamizu A;Schreiber S;Clevers H;Verrey F;Rosenstiel P;Penninger JM
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Penninger JM
影响因子：
64.8
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Gaebler C;Wang Z;Lorenzi JCC;Muecksch F;Finkin S;Tokuyama M;Cho A;Jankovic M;Schaefer-Babajew D;Oliveira TY;Cipolla M;Viant C;Barnes CO;Bram Y;Breton G;Hägglöf T;Mendoza P;Hurley A;Turroja M;Gordon K;Millard KG;Ramos V;Schmidt F;Weisblum Y;Jha D;Tankelevich M;Martinez-Delgado G;Yee J;Patel R;Dizon J;Unson-O'Brien C;Shimeliovich I;Robbiani DF;Zhao Z;Gazumyan A;Schwartz RE;Hatziioannou T;Bjorkman PJ;Mehandru S;Bieniasz PD;Caskey M;Nussenzweig MC
通讯作者：
Nussenzweig MC
影响因子：
4.6
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通讯作者：
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64.8
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通讯作者：
Mucida, Daniel