Identification and characterization of permissive cells to dengue virus infection in human hematopoietic stem and progenitor cells

Alan Y. Hsu; Tzu Chuan Ho; Mei Ling Lai; Sia Seng Tan; Tsai Yun Chen; Meed Lee; Yu Wen Chien; Ya Ping Chen; Guey Chuen Perng

doi:10.1111/trf.15416

Identification and characterization of permissive cells to dengue virus infection in human hematopoietic stem and progenitor cells

Alan Y. Hsu, Tzu Chuan Ho, Mei Ling Lai, Sia Seng Tan, Tsai Yun Chen, Meed Lee, Yu Wen Chien, Ya Ping Chen, Guey Chuen Perng

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6 Citations (Scopus)

Abstract

BACKGROUND: Dengue virus (DENV) is a significant threat to public health in tropical and subtropical regions, where the frequency of human migration is increasing. Transmission of DENV from donors to recipients after hematopoietic stem cell transplantation has been steadily described. However, the underlying mechanisms remain unclear. STUDY DESIGN AND METHODS: Freshly isolated bone marrow (BM) was subjected to DENV infection, followed by multicolor fluorescence-activated cell sorting (FACS) analysis. Virus in supernatants was collected and analyzed by plaque assay. RESULTS: DENV-1 to DENV-4 could effectively infect freshly obtained BM and produced infectious virus. DENV infection did not change the quantitative population of hematopoietic stem and progenitor cells (HSPCs), megakaryocytic progenitor cells (MkPs) and megakaryocytes. Additionally, DENV antigen, nonstructural protein 1, was enriched in HSPCs and MkPs of DENV infected marrow cells. CD34+, CD133+, or CD61+ cells sorted out from BM were not only the major contributing targets facilitating the DENV infection directly but also facilitated the spread of DENV into other cells when cocultured. CONCLUSION: Results suggest that DENV can efficiently infect HSPCs, which might jeopardize the recipients if DENV-infected cells were subsequently used. We therefore raise the need for DENV screening for both the donors and recipients of hematopoietic stem cell transplantation, especially for donors exposed to endemic areas, to mitigate DENV infection in immunocompromised recipients.

Original language	English
Pages (from-to)	2938-2951
Number of pages	14
Journal	Transfusion
Volume	59
Issue number	9
DOIs	https://doi.org/10.1111/trf.15416
Publication status	Published - 2019 Sept 1

All Science Journal Classification (ASJC) codes

Immunology and Allergy
Immunology
Hematology

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10.1111/trf.15416

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@article{ee6d7c171464464590207a228288861f,

title = "Identification and characterization of permissive cells to dengue virus infection in human hematopoietic stem and progenitor cells",

abstract = "BACKGROUND: Dengue virus (DENV) is a significant threat to public health in tropical and subtropical regions, where the frequency of human migration is increasing. Transmission of DENV from donors to recipients after hematopoietic stem cell transplantation has been steadily described. However, the underlying mechanisms remain unclear. STUDY DESIGN AND METHODS: Freshly isolated bone marrow (BM) was subjected to DENV infection, followed by multicolor fluorescence-activated cell sorting (FACS) analysis. Virus in supernatants was collected and analyzed by plaque assay. RESULTS: DENV-1 to DENV-4 could effectively infect freshly obtained BM and produced infectious virus. DENV infection did not change the quantitative population of hematopoietic stem and progenitor cells (HSPCs), megakaryocytic progenitor cells (MkPs) and megakaryocytes. Additionally, DENV antigen, nonstructural protein 1, was enriched in HSPCs and MkPs of DENV infected marrow cells. CD34+, CD133+, or CD61+ cells sorted out from BM were not only the major contributing targets facilitating the DENV infection directly but also facilitated the spread of DENV into other cells when cocultured. CONCLUSION: Results suggest that DENV can efficiently infect HSPCs, which might jeopardize the recipients if DENV-infected cells were subsequently used. We therefore raise the need for DENV screening for both the donors and recipients of hematopoietic stem cell transplantation, especially for donors exposed to endemic areas, to mitigate DENV infection in immunocompromised recipients.",

author = "Hsu, {Alan Y.} and Ho, {Tzu Chuan} and Lai, {Mei Ling} and Tan, {Sia Seng} and Chen, {Tsai Yun} and Meed Lee and Chien, {Yu Wen} and Chen, {Ya Ping} and Perng, {Guey Chuen}",

note = "Funding Information: The authors acknowledge Mr. Dun Yao Hu, Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, for his technical assistance in DENV infection in BM. AYH and TCH designed and performed the most experiments and analysis; SST handled the patient specimens and performed the plaque assays; ML performed the experiment of hematopoietic progenitor and megakaryocytic cell expansion and differentiation from BM; MLL performed FACS analysis; TYC assisted human BM collection and IRB approval; YWC provided technical assistance in sample preparations; YPC assisted the collection of PBMCs and BM, IRB approval, and data analysis; AYH, YPC, and GCP wrote the manuscript; GCP designed the overall study. Funding Information: This research was supported, in part, by the Ministry of Education, Taiwan, R.O.C., The Aim for the Top University Project to the National Cheng Kung University (GCP), Ministry of Health and Welfare (MOHW104-CDC-C-114-114901) (GCP), and National Science Council Grant (NSC 102-2320-B-006–049 and MOST 103 - 2320 - B - 006 - 030 - MY3) (GCP). Publisher Copyright: {\textcopyright} 2019 AABB",

year = "2019",

month = sep,

day = "1",

doi = "10.1111/trf.15416",

language = "English",

volume = "59",

pages = "2938--2951",

journal = "Transfusion",

issn = "0041-1132",

publisher = "Wiley-Blackwell",

number = "9",

}

TY - JOUR

T1 - Identification and characterization of permissive cells to dengue virus infection in human hematopoietic stem and progenitor cells

AU - Hsu, Alan Y.

AU - Ho, Tzu Chuan

AU - Lai, Mei Ling

AU - Tan, Sia Seng

AU - Chen, Tsai Yun

AU - Lee, Meed

AU - Chien, Yu Wen

AU - Chen, Ya Ping

AU - Perng, Guey Chuen

N1 - Funding Information: The authors acknowledge Mr. Dun Yao Hu, Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, for his technical assistance in DENV infection in BM. AYH and TCH designed and performed the most experiments and analysis; SST handled the patient specimens and performed the plaque assays; ML performed the experiment of hematopoietic progenitor and megakaryocytic cell expansion and differentiation from BM; MLL performed FACS analysis; TYC assisted human BM collection and IRB approval; YWC provided technical assistance in sample preparations; YPC assisted the collection of PBMCs and BM, IRB approval, and data analysis; AYH, YPC, and GCP wrote the manuscript; GCP designed the overall study. Funding Information: This research was supported, in part, by the Ministry of Education, Taiwan, R.O.C., The Aim for the Top University Project to the National Cheng Kung University (GCP), Ministry of Health and Welfare (MOHW104-CDC-C-114-114901) (GCP), and National Science Council Grant (NSC 102-2320-B-006–049 and MOST 103 - 2320 - B - 006 - 030 - MY3) (GCP). Publisher Copyright: © 2019 AABB

PY - 2019/9/1

Y1 - 2019/9/1

N2 - BACKGROUND: Dengue virus (DENV) is a significant threat to public health in tropical and subtropical regions, where the frequency of human migration is increasing. Transmission of DENV from donors to recipients after hematopoietic stem cell transplantation has been steadily described. However, the underlying mechanisms remain unclear. STUDY DESIGN AND METHODS: Freshly isolated bone marrow (BM) was subjected to DENV infection, followed by multicolor fluorescence-activated cell sorting (FACS) analysis. Virus in supernatants was collected and analyzed by plaque assay. RESULTS: DENV-1 to DENV-4 could effectively infect freshly obtained BM and produced infectious virus. DENV infection did not change the quantitative population of hematopoietic stem and progenitor cells (HSPCs), megakaryocytic progenitor cells (MkPs) and megakaryocytes. Additionally, DENV antigen, nonstructural protein 1, was enriched in HSPCs and MkPs of DENV infected marrow cells. CD34+, CD133+, or CD61+ cells sorted out from BM were not only the major contributing targets facilitating the DENV infection directly but also facilitated the spread of DENV into other cells when cocultured. CONCLUSION: Results suggest that DENV can efficiently infect HSPCs, which might jeopardize the recipients if DENV-infected cells were subsequently used. We therefore raise the need for DENV screening for both the donors and recipients of hematopoietic stem cell transplantation, especially for donors exposed to endemic areas, to mitigate DENV infection in immunocompromised recipients.

AB - BACKGROUND: Dengue virus (DENV) is a significant threat to public health in tropical and subtropical regions, where the frequency of human migration is increasing. Transmission of DENV from donors to recipients after hematopoietic stem cell transplantation has been steadily described. However, the underlying mechanisms remain unclear. STUDY DESIGN AND METHODS: Freshly isolated bone marrow (BM) was subjected to DENV infection, followed by multicolor fluorescence-activated cell sorting (FACS) analysis. Virus in supernatants was collected and analyzed by plaque assay. RESULTS: DENV-1 to DENV-4 could effectively infect freshly obtained BM and produced infectious virus. DENV infection did not change the quantitative population of hematopoietic stem and progenitor cells (HSPCs), megakaryocytic progenitor cells (MkPs) and megakaryocytes. Additionally, DENV antigen, nonstructural protein 1, was enriched in HSPCs and MkPs of DENV infected marrow cells. CD34+, CD133+, or CD61+ cells sorted out from BM were not only the major contributing targets facilitating the DENV infection directly but also facilitated the spread of DENV into other cells when cocultured. CONCLUSION: Results suggest that DENV can efficiently infect HSPCs, which might jeopardize the recipients if DENV-infected cells were subsequently used. We therefore raise the need for DENV screening for both the donors and recipients of hematopoietic stem cell transplantation, especially for donors exposed to endemic areas, to mitigate DENV infection in immunocompromised recipients.

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EP - 2951

JO - Transfusion

JF - Transfusion

IS - 9

ER -

Identification and characterization of permissive cells to dengue virus infection in human hematopoietic stem and progenitor cells

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