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DataSheet_1_Interspecies comparison of the early transcriptomic changes associated with hepatitis B virus exposure in human and macaque immune cell populations.docx

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posted on 2023-09-01, 04:24 authored by Armando Andres Roca Suarez, Séverine Planel, Xavier Grand, Céline Couturier, Trang Tran, Fabrice Porcheray, Jérémie Becker, Frédéric Reynier, Ana Delgado, Elodie Cascales, Loïc Peyrot, Andrea Tamellini, Adrien Saliou, Céline Elie, Chloé Baum, Bao Quoc Vuong, Barbara Testoni, Pierre Roques, Fabien Zoulim, Uzma Hasan, Isabelle Chemin
Background and aims

Hepatitis 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.

Methods

We 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.

Results

HBV 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.

Conclusion

Our 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.

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