机构:[1]Organ Transplant Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.中山大学附属第一医院[2]Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China.[3]Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Sun Yat-Sen University, Guangzhou 510080, China.[4]Guangdong Provincial International Cooperation Based of Science and Technology (Organ Transplantation), Sun Yat-Sen University, Guangzhou 510080, China.[5]Department of Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510080, China.
BK polyomavirus (BKPyV) infection is the main factor affecting the prognosis of kidney transplant recipients, as no antiviral agent is yet available. A better understanding of the renal-cell-type tropism of BKPyV can serve to develop new treatment strategies. In this study, the single-cell transcriptomic analysis demonstrated that the ranking of BKPyV tropism for the kidney was proximal tubule cells (PT), collecting duct cells (CD), and glomerular endothelial cells (GEC) according to the signature of renal cell type and immune microenvironment. In normal kidneys, we found that BKPyV infection-related transcription factors P65 and CEBPB were PT-specific transcription factors, and PT showed higher glycolysis/gluconeogenesis activities than CD and GEC. Furthermore, in the BKPyV-infected kidneys, the percentage of late viral transcripts in PT was significantly higher than in CD and GEC. In addition, PT had the smallest cell-cell interactions with immune cells compared to CD and GEC in both normal and BKPyV-infected kidneys. Subsequently, we indirectly demonstrated the ranking of BKPyV tropism via the clinical observation of sequential biopsies. Together, our results provided in-depth insights into the renal cell-type tropism of BKPyV in vivo at single-cell resolution and proposed a novel antiviral target.
基金:
This work was supported by grants from the National Natural Science Foundation of China
(82270786, G.H.) and the Basic and Applied Basic Research Foundation of Guangdong Province
(2020A1515110075, X.C.).
第一作者机构:[1]Organ Transplant Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.[2]Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China.[3]Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Sun Yat-Sen University, Guangzhou 510080, China.[4]Guangdong Provincial International Cooperation Based of Science and Technology (Organ Transplantation), Sun Yat-Sen University, Guangzhou 510080, China.
共同第一作者:
通讯作者:
通讯机构:[1]Organ Transplant Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.[3]Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Sun Yat-Sen University, Guangzhou 510080, China.[4]Guangdong Provincial International Cooperation Based of Science and Technology (Organ Transplantation), Sun Yat-Sen University, Guangzhou 510080, China.
推荐引用方式(GB/T 7714):
Yang Feng,Chen Xutao,Zhang Hui,et al.Single-Cell Transcriptome Identifies the Renal Cell Type Tropism of Human BK Polyomavirus[J].INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES.2023,24(2):doi:10.3390/ijms24021330.
APA:
Yang Feng,Chen Xutao,Zhang Hui,Zhao Guo-Dong,Yang Huifei...&Huang Gang.(2023).Single-Cell Transcriptome Identifies the Renal Cell Type Tropism of Human BK Polyomavirus.INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,24,(2)
MLA:
Yang Feng,et al."Single-Cell Transcriptome Identifies the Renal Cell Type Tropism of Human BK Polyomavirus".INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 24..2(2023)