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Parvovirus B19 targets hematopoietic stem cells to disrupt multilineage differentiation and drive pancytopenia

Cell Death & Differentiation (2026)Cite this article

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Abstract

Human parvovirus B19 (B19V) infection is a significant but underrecognized complication, commonly linked not only to aplastic anemia but also pancytopenia, especially in hematopoietic stem cell transplantation (HSCT) recipients. While B19V’s tropism for erythroid progenitor cells (EPCs) is well-documented, its restriction to EPCs fails to fully explain the pathogenesis of pancytopenia. In this study, we used PrimeFlow RNA assay, and single-cell full-length transcriptome sequencing (scFAST-seq) to show that B19V could infect hematopoietic stem cells (HSCs) and initiate viral transcription, resulting in increased apoptosis, impaired self-renewal and multilineage differentiation of HSCs, which may contribute directly to pancytopenia. Further analysis revealed that B19V could activate the JAK2/STAT5 signaling pathway in HSCs to promote viral persistence. Pharmacological inhibition with baricitinib markedly reduced the viral load and partially restored hematopoietic differentiation capacity in vitro. Taken together, our findings reveal B19V as a previously unrecognized HSC-tropic virus that disrupts function of HSCs and may drive pancytopenia. Targeting the JAK2/STAT5 signaling by baricitinib shows promising therapeutic potential for reversing virus-induced bone marrow failure. This work not only deepens our understanding of viral tropism and pathogenesis in the hematopoietic niche, but also opens up new possibilities for treating bone marrow damage after transplantation and in other hematological diseases.

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Fig. 1: B19V infection induces pancytopenia in HSCT and non-HSCT populations.
Fig. 2: B19V infection extends beyond EPCs.
Fig. 3: B19V transcription initiates in HSCs.
Fig. 4: B19V infection disrupts HSC function and survival.
Fig. 5: B19V-infected HSCs exhibit reduced differentiation potential.
Fig. 6: Baricitinib may be a potential strategy for B19V infection.

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Data availability

The raw sequence data reported in this paper have been deposited in the Genome Sequence Archive in National Genomics Data Center, China National Center for Bioinformation / Beijing Institute of Genomics, Chinese Academy of Sciences (GSA-Human: HRA009811 and HRA011660) that are publicly accessible at https://ngdc.cncb.ac.cn/gsa-human. For other original data regarding this manuscript, please contact the corresponding author at huangxiaojun@bjmu.edu.cn.

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Funding

This work was supported by the Beijing Research Ward Excellence Program (No. BRWEP2024W134080112), Noncommunicable Chronic Diseases-National Science and Technology Major Project (No. 2023ZD0502405), Beijing Nova Program (No. 20220484076), Major Program of the National Natural Science Foundation of China (No. 82293630), and Beijing Municipal Science & Technology Commission (No. Z211100002921071).

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Author notes

  1. These authors contributed equally: Xu-Ying Pei, Zhuo-Jun Liu.

Authors and Affiliations

  1. Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China

    Xu-Ying Pei, Zhuo-Jun Liu, Qiang Fu, Xiao-Su Zhao, Yan Wei, Yu-Qian Sun, Lan-Ping Xu, Yu Wang, Xiao-Hui Zhang, Xiang-Yu Zhao & Xiao-Jun Huang

  2. Peking-Tsinghua Center for Life Sciences, Beijing, China

    Hsiang-Ying Lee, Qi Hu & Xiao-Jun Huang

  3. School of Life Sciences, Peking University, Beijing, China

    Hsiang-Ying Lee & Qi Hu

  4. Institute of Systems Biomedicine, Department of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Peking University Health Science Center, Beijing, China

    Fu-Ping You

  5. Collaborative Innovation Center of Hematology, Beijing University, Beijing, China

    Xiang-Yu Zhao & Xiao-Jun Huang

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Contributions

XJH, XYP and XYZ conceived and designed the study. XYP and ZJL performed the experiments, analyzed data and wrote the manuscript. QF, HYL, QH, XSZ, Y.Wei, FPY, and YQS collected data and help for data analysis. LPX, Y.Wang, and XHZ participated in the drafting of the article. All authors gave final approval for the manuscript. We thank Professor Wuxiang Guan from Wuhan Institute of Virology, Chinese Academy of Science, for his assistance in the in vitro research on B19V.

Corresponding authors

Correspondence to Xiang-Yu Zhao or Xiao-Jun Huang.

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The study was approved by the ethics committee of Peking University People’s Hospital and was in accordance with the Declaration of Helsinki. Written informed consent was obtained from all participants.

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Pei, XY., Liu, ZJ., Fu, Q. et al. Parvovirus B19 targets hematopoietic stem cells to disrupt multilineage differentiation and drive pancytopenia. Cell Death Differ (2026). https://doi.org/10.1038/s41418-026-01671-3

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