Nucleocapsid protein accumulates in renal tubular epithelium of a post-COVID-19 patient.

Nucleocapsid protein accumulates in renal tubular epithelium of a post-COVID-19 patient.
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DOI:
10.1128/spectrum.03029-23
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发表时间:
2023-12-12
影响因子:
3.7
通讯作者:
--
中科院分区:
生物学1区
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在这项研究中,我们调查了是否可以(I)在致命冠状病毒病2019(新冠肺炎)患者的身体肾脏中检测到严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)病毒蛋白和病毒颗粒,以及(Ii)在抗击SARS-CoV-2感染几个月后在肾衰竭患者的肾活检中检测到SARS-CoV-2病毒蛋白和病毒颗粒。利用荧光显微镜,在SARS-CoV-2感染的Vero细胞上验证了针对病毒蛋白[核衣壳蛋白、膜蛋白(M)、非结构蛋白(NSP)3、4和13]和双链RNA(DsRNA)的抗体。在SARS-CoV-2产生细胞中,在充满脂质的电子荧光(白色)隔间中检测到双链RNA。在1例急性肾功能衰竭患者的肾脏中,检测到SARS-CoV-2核衣壳N蛋白在肾小管上皮细胞中积聚。相反,在这些区域没有检测到其他病毒蛋白(M、NSP3、4、13)和dsRNA,这表明这些患者的肾脏没有发生病毒复制。高分辨免疫电子显微镜显示N蛋白在高尔基体样结构中积聚,但细胞内没有病毒颗粒。患者肾脏高尔基体样结构中N蛋白的存在提示该蛋白在新冠肺炎术后肾脏并发症中可能具有不可预见的作用。尽管冠状病毒病2019年(新冠肺炎)大流行正在缓慢发展为一种常规传染病,但严重急性呼吸综合征冠状病毒2(SARS-CoV-2)病毒感染的长期影响仍未被很好地了解。其中一个问题是,许多新冠肺炎病例会出现急性肾损伤。尽管如此,SARS-CoV-2病毒是否进入并在肾脏组织中活跃复制,以及SARS-CoV-2病毒颗粒是否可以在感染期间或感染后在肾脏中检测到,仍存在激烈的争论。在这里,我们证明了在已经康复的新冠肺炎患者的肾小管上皮细胞中检测到核衣壳N蛋白。大量产生的N蛋白的存在而没有病毒复制的迹象,可能会导致肾脏疾病的复发,并对免疫系统产生持续的影响。
In this study, we investigated whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins and virus particles can be detected (i) in post-mortem kidney of fatal coronavirus disease 2019 (COVID-19) patients and (ii) in renal biopsy of patients suffering from kidney failure months after combating a SARS-CoV-2 infection. Using fluorescence microscopy, antibodies against viral proteins [nucleocapsid, membrane (M), non-structural proteins (nsp) 3, 4, and 13] and double-stranded RNA (dsRNA) were validated on SARS-CoV-2-infected Vero cells. dsRNA was detected in lipid-filled electron-lucent (white) compartments in SARS-CoV-2-producing cells. In the kidney of a patient with acute kidney failure, accumulation of SARS-CoV-2 nucleocapsid N protein was detected in tubular epithelium. In contrast, none of the other viral proteins (M, nsp3, 4, 13) nor dsRNA was detected in these regions, suggesting that no viral replication takes place in the kidney of these patients. High-resolution immunoelectron microscopy demonstrated N protein accumulation in Golgi-like structures but absence of intracellular virus particles. The presence of the N protein in Golgi-like structures in kidney of patients suggests that this protein may have an unforeseen role in post-COVID-19 renal complications. Even though the coronavirus disease 2019 (COVID-19) pandemic is slowly developing into a conventional infectious disease, the long-term effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infection are still not well understood. One of the problems is that many COVID-19 cases develop acute kidney injuries. Still, it is heavily debated whether SARS-CoV-2 virus enters and actively replicates in kidney tissue and if SARS-CoV-2 virus particles can be detected in kidney during or post-infection. Here, we demonstrated that nucleocapsid N protein was detected in kidney tubular epithelium of patients that already recovered form COVID-19. The presence of the abundantly produced N protein without signs of viral replication could have implications for the recurrence of kidney disease and have a continuing effect on the immune system.
DOI: 10.1016/j.kint.2021.01.004
发表时间: 2021-04
影响因子: 19.6
作者:
Bullock HA;Goldsmith CS;Miller SE
通讯作者: Miller SE
DOI: 10.1172/jci161944
发表时间: 2023-03-15
影响因子: 15.9
作者:
Bedard, Melissa;van der Niet, Sanne;Bernard, Elliott M.;Babunovic, Gregory;Cheng, Tan-Yun;Aylan, Beren;Grootemaat, Anita E.;Raman, Sahadevan;Botella, Laure;Ishikawa, Eri;O'Sullivan, Mary P.;Mayfield, Jacob A.;O'Leary, Seonadh;Buter, Jeffrey;Minnaard, Adriaan J.;Fortune, Sarah M.;Murphy, Leon O.;Ory, Daniel S.;Keane, Joseph;Yamasaki, Sho;Gutierrez, Maximiliano G.;van der Wel, Nicole;Moody, D. Branch
通讯作者: Moody, D. Branch
DOI: 10.1053/j.ajkd.2020.12.007
发表时间: 2021-04
期刊: American journal of kidney diseases : the official journal of the National Kidney Foundation
影响因子: --
作者:
Moledina DG;Simonov M;Yamamoto Y;Alausa J;Arora T;Biswas A;Cantley LG;Ghazi L;Greenberg JH;Hinchcliff M;Huang C;Mansour SG;Martin M;Peixoto A;Schulz W;Subair L;Testani JM;Ugwuowo U;Young P;Wilson FP
通讯作者: Wilson FP
DOI: 10.3390/v13061115
发表时间: 2021-06-10
期刊: Viruses
影响因子: --
作者:
Bai Z;Cao Y;Liu W;Li J
通讯作者: Li J
DOI: 10.1371/journal.ppat.1009127
发表时间: 2020-12
期刊: PLoS pathogens
影响因子: 6.7
作者:
Dias SSG;Soares VC;Ferreira AC;Sacramento CQ;Fintelman-Rodrigues N;Temerozo JR;Teixeira L;Nunes da Silva MA;Barreto E;Mattos M;de Freitas CS;Azevedo-Quintanilha IG;Manso PPA;Miranda MD;Siqueira MM;Hottz ED;Pão CRR;Bou-Habib DC;Barreto-Vieira DF;Bozza FA;Souza TML;Bozza PT
通讯作者: Bozza PT