Interspecies comparison of the early transcriptomic changes associated with hepatitis B virus exposure in human and macaque immune cell populations

Frontiers in Cellular and Infection Microbiology

Cellular and Infection Microbiology

Andrea Tamellini¹  Adrien Saliou¹  Jérémie Becker¹  Frédéric Reynier¹  Fabrice Porcheray¹  Chloé Baum¹  Séverine Planel¹  Céline Couturier¹  Trang Tran¹  Elodie Cascales¹  Loïc Peyrot¹  Céline Elie¹  Ana Delgado¹  Pierre Roques²  Bao Quoc Vuong³  Uzma Hasan⁴  Barbara Testoni⁵  Xavier Grand⁵  Isabelle Chemin⁵  Armando Andres Roca Suarez⁵  Fabien Zoulim⁶ 

[1] BIOASTER, Institut de Recherche Technologique, Lyon, France;CEA, Institut François Jacob, Fontenay-aux-Roses, France;Inserm, U1184, Fontenay-aux-Roses and Université Paris-Saclay, Orsay, France;Institut Pasteur de Guinée, Conakry, Guinea;Department of Biology, The City College of New York, New York, NY, United States;The Graduate Center, The City University of New York, New York, NY, United States;INSERM U1052, CNRS UMR-5286, Cancer Research Center of Lyon (CRCL), Lyon, France;INSERM U1111, Centre International de Recherche en Infectiologie (CIRI), Lyon, France;INSERM U1052, CNRS UMR-5286, Cancer Research Center of Lyon (CRCL), Lyon, France;University of Lyon, Université Claude-Bernard (UCBL), Lyon, France;Hepatology Institute of Lyon, Lyon, France;INSERM U1052, CNRS UMR-5286, Cancer Research Center of Lyon (CRCL), Lyon, France;University of Lyon, Université Claude-Bernard (UCBL), Lyon, France;Hepatology Institute of Lyon, Lyon, France;Department of Hepatology, Croix Rousse Hospital, Hospices Civils de Lyon, Lyon, France;

关键词: HBV;    PBMC;    transcriptomics;    immune response;    macaque;   

DOI  :  10.3389/fcimb.2023.1248782

 received in 2023-06-27, accepted in 2023-08-15,  发布年份 2023

来源: Frontiers

【 摘 要 】

Background and aimsHepatitis B virus (HBV) infection affects 300 million individuals worldwide, representing a major factor for the development of hepatic complications. Although existing antivirals are effective in suppressing replication, eradication of HBV is not achieved. Therefore, a multi-faceted approach involving antivirals and immunomodulatory agents is required. Non-human primates are widely used in pre-clinical studies due to their close evolutionary relationship to humans. Nonetheless, it is fundamental to identify the differences in immune response between humans and these models. Thus, we performed a transcriptomic characterization and interspecies comparison of the early immune responses to HBV in human and cynomolgus macaques.MethodsWe characterized early transcriptomic changes in human and cynomolgus B cells, T cells, myeloid and plasmacytoid dendritic cells (pDC) exposed to HBV ex vivo for 2 hours. Differentially-expressed genes were further compared to the profiles of HBV-infected patients using publicly-available single-cell data.ResultsHBV induced a wide variety of transcriptional changes in all cell types, with common genes between species representing only a small proportion. In particular, interferon gamma signaling was repressed in human pDCs. At the gene level, interferon gamma inducible protein 16 (IFI16) was upregulated in macaque pDCs, while downregulated in humans. Moreover, IFI16 expression in pDCs from chronic HBV-infected patients anti-paralleled serum HBsAg levels.ConclusionOur characterization of early transcriptomic changes induced by HBV in humans and cynomolgus macaques represents a useful resource for the identification of shared and divergent host responses, as well as potential immune targets against HBV.

【 授权许可】

Unknown   
Copyright © 2023 Roca Suarez, Planel, Grand, Couturier, Tran, Porcheray, Becker, Reynier, Delgado, Cascales, Peyrot, Tamellini, Saliou, Elie, Baum, Vuong, Testoni, Roques, Zoulim, Hasan and Chemin