Single-cell RNA sequencing reveals intrahepatic signature related to pathobiology of duck hepatitis A virus type 3 (DHAV-3) infection

DHAV-3 is one of the main causative agents of duck viral hepatitis (DVH), an acute and highly lethal infectious disease in duck industry. However, the understanding of the pathogenesis of this virus in ducklings is limited. To dissect the molecular characteristics associated with pathobiology of duc...

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Main Authors: Yunsheng Zhang, Dingbang Ding, Shaofei Li, Qiong Pan, Jinlong Ru, Haonan Zhao, Guang Yao, Jie Wei, Shuaiqin Wang, Shuisheng Hou, Xia Wang
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Poultry Science
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Online Access:http://www.sciencedirect.com/science/article/pii/S0032579125000355
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author Yunsheng Zhang
Dingbang Ding
Shaofei Li
Qiong Pan
Jinlong Ru
Haonan Zhao
Guang Yao
Jie Wei
Shuaiqin Wang
Shuisheng Hou
Xia Wang
author_facet Yunsheng Zhang
Dingbang Ding
Shaofei Li
Qiong Pan
Jinlong Ru
Haonan Zhao
Guang Yao
Jie Wei
Shuaiqin Wang
Shuisheng Hou
Xia Wang
author_sort Yunsheng Zhang
collection DOAJ
description DHAV-3 is one of the main causative agents of duck viral hepatitis (DVH), an acute and highly lethal infectious disease in duck industry. However, the understanding of the pathogenesis of this virus in ducklings is limited. To dissect the molecular characteristics associated with pathobiology of ducklings to DHAV-3, we applied single-cell RNA-sequencing approach to profile the transcriptome of 1.4 million cells from 14 livers of DHAV-3 susceptible (S) and resistant (R) ducklings during viral infection and 4 uninfected healthy controls. We found that infected S ducks exhibited the activation of type I and II interferon pathways with elevated expression of interferon-stimulated genes (ISGs) compared to infected R ducks and healthy controls. DHAV-3 promoted proinflammatory phenotype and inhibited the cell apoptosis pathway of Kupffer cells of S ducks. Furthermore, we observed the elevated expression of host factor PLAC8 in S ducks and validated its ability to facilitate the infection of DHAV-3. We identified significant dysregulation of various genes in complement and coagulation cascades in hepatocytes2 exclusive to S ducks, together with over-secretion of ANGPTL4 from endothelial cells in S ducks which is confirmed to promote cellular migration, suggesting etiology of coagulopathic complications in ducks with severe DVH. Collectively, this study provides a rich resource for understanding the inflammatory immune signatures and cell communications underlying the pathogenesis of DHAV-3 infection, which may accelerate the development of better diagnostic methods and strategies for controlling this disease.
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spelling doaj-art-dfe3763b0e434b55be3a393f385583832025-01-13T04:18:17ZengElsevierPoultry Science0032-57912025-02-011042104798Single-cell RNA sequencing reveals intrahepatic signature related to pathobiology of duck hepatitis A virus type 3 (DHAV-3) infectionYunsheng Zhang0Dingbang Ding1Shaofei Li2Qiong Pan3Jinlong Ru4Haonan Zhao5Guang Yao6Jie Wei7Shuaiqin Wang8Shuisheng Hou9Xia Wang10Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, PR ChinaCollege of Animal Science and Technology, Northwest A&F University, Yangling 712100 Shaanxi, PR ChinaCollege of Animal Science and Technology, Northwest A&F University, Yangling 712100 Shaanxi, PR ChinaDepartment of Molecular and Cellular Biology, University of Arizona, Tucson 85721 AZ, United StatesCollege of Animal Science and Technology, Northwest A&F University, Yangling 712100 Shaanxi, PR ChinaCollege of Animal Science and Technology, Northwest A&F University, Yangling 712100 Shaanxi, PR ChinaDepartment of Molecular and Cellular Biology, University of Arizona, Tucson 85721 AZ, United StatesInstitute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, PR ChinaInstitute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, PR ChinaInstitute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, PR China; Corresponding authors.College of Animal Science and Technology, Northwest A&F University, Yangling 712100 Shaanxi, PR China; Corresponding authors.DHAV-3 is one of the main causative agents of duck viral hepatitis (DVH), an acute and highly lethal infectious disease in duck industry. However, the understanding of the pathogenesis of this virus in ducklings is limited. To dissect the molecular characteristics associated with pathobiology of ducklings to DHAV-3, we applied single-cell RNA-sequencing approach to profile the transcriptome of 1.4 million cells from 14 livers of DHAV-3 susceptible (S) and resistant (R) ducklings during viral infection and 4 uninfected healthy controls. We found that infected S ducks exhibited the activation of type I and II interferon pathways with elevated expression of interferon-stimulated genes (ISGs) compared to infected R ducks and healthy controls. DHAV-3 promoted proinflammatory phenotype and inhibited the cell apoptosis pathway of Kupffer cells of S ducks. Furthermore, we observed the elevated expression of host factor PLAC8 in S ducks and validated its ability to facilitate the infection of DHAV-3. We identified significant dysregulation of various genes in complement and coagulation cascades in hepatocytes2 exclusive to S ducks, together with over-secretion of ANGPTL4 from endothelial cells in S ducks which is confirmed to promote cellular migration, suggesting etiology of coagulopathic complications in ducks with severe DVH. Collectively, this study provides a rich resource for understanding the inflammatory immune signatures and cell communications underlying the pathogenesis of DHAV-3 infection, which may accelerate the development of better diagnostic methods and strategies for controlling this disease.http://www.sciencedirect.com/science/article/pii/S0032579125000355scRNA-seqduckDHAV-3PLAC8Coagulation
spellingShingle Yunsheng Zhang
Dingbang Ding
Shaofei Li
Qiong Pan
Jinlong Ru
Haonan Zhao
Guang Yao
Jie Wei
Shuaiqin Wang
Shuisheng Hou
Xia Wang
Single-cell RNA sequencing reveals intrahepatic signature related to pathobiology of duck hepatitis A virus type 3 (DHAV-3) infection
Poultry Science
scRNA-seq
duck
DHAV-3
PLAC8
Coagulation
title Single-cell RNA sequencing reveals intrahepatic signature related to pathobiology of duck hepatitis A virus type 3 (DHAV-3) infection
title_full Single-cell RNA sequencing reveals intrahepatic signature related to pathobiology of duck hepatitis A virus type 3 (DHAV-3) infection
title_fullStr Single-cell RNA sequencing reveals intrahepatic signature related to pathobiology of duck hepatitis A virus type 3 (DHAV-3) infection
title_full_unstemmed Single-cell RNA sequencing reveals intrahepatic signature related to pathobiology of duck hepatitis A virus type 3 (DHAV-3) infection
title_short Single-cell RNA sequencing reveals intrahepatic signature related to pathobiology of duck hepatitis A virus type 3 (DHAV-3) infection
title_sort single cell rna sequencing reveals intrahepatic signature related to pathobiology of duck hepatitis a virus type 3 dhav 3 infection
topic scRNA-seq
duck
DHAV-3
PLAC8
Coagulation
url http://www.sciencedirect.com/science/article/pii/S0032579125000355
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