Zika virus infects human osteoclasts and blocks differentiation and bone resorption

Noreen Mumtaz; Marijke Koedam; Johannes P T M van Leeuwen; Marion P G Koopmans; Bram C J van der Eerden; Barry Rockx

doi:10.1080/22221751.2022.2086069

Zika virus infects human osteoclasts and blocks differentiation and bone resorption

Noreen Mumtaz, Marijke Koedam, Johannes P T M van Leeuwen, Marion P G Koopmans, Bram C J van der Eerden, Barry Rockx^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Bone-related complications are commonly reported following arbovirus infection. These arboviruses are known to disturb bone-remodeling and induce inflammatory bone loss via increased activity of bone resorbing osteoclasts (OCs). We previously showed that Zika virus (ZIKV) could disturb the function of bone forming osteoblasts, but the susceptibility of OCs to ZIKV infection is not known. Here, we investigated the effect of ZIKV infection on osteoclastogenesis and report that infection of pre- and early OCs with ZIKV significantly reduced the osteoclast formation and bone resorption. Interestingly, infection of pre-OCs with a low dose ZIKV infection in the presence of flavivirus cross-reacting antibodies recapitulated the phenotype observed with a high viral dose, suggesting a role for antibody-dependent enhancement in ZIKV-associated bone pathology. In conclusion, we have characterized a primary in vitro model to study the role of osteoclastogenesis in ZIKV pathogenesis, which will help to identify possible new targets for developing therapeutic and preventive measures.

Original language	English
Pages (from-to)	1621-1634
Number of pages	14
Journal	Emerging Microbes & Infections
Volume	11
Issue number	1
DOIs	https://doi.org/10.1080/22221751.2022.2086069
Publication status	Published - Dec 2022

Bibliographical note

Funding Information:
This work was supported in part by ZonMW under grant number 522003001 (project: ZikaRisk “Risk of Zika virus introductions for the Netherlands”) and by the European Union’s Horizon 2020 Research and Innovation Programme under grant number 734548 (project: ZIKAlliance).

Publisher Copyright:
© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd.

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Cite this

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title = "Zika virus infects human osteoclasts and blocks differentiation and bone resorption",

abstract = "Bone-related complications are commonly reported following arbovirus infection. These arboviruses are known to disturb bone-remodeling and induce inflammatory bone loss via increased activity of bone resorbing osteoclasts (OCs). We previously showed that Zika virus (ZIKV) could disturb the function of bone forming osteoblasts, but the susceptibility of OCs to ZIKV infection is not known. Here, we investigated the effect of ZIKV infection on osteoclastogenesis and report that infection of pre- and early OCs with ZIKV significantly reduced the osteoclast formation and bone resorption. Interestingly, infection of pre-OCs with a low dose ZIKV infection in the presence of flavivirus cross-reacting antibodies recapitulated the phenotype observed with a high viral dose, suggesting a role for antibody-dependent enhancement in ZIKV-associated bone pathology. In conclusion, we have characterized a primary in vitro model to study the role of osteoclastogenesis in ZIKV pathogenesis, which will help to identify possible new targets for developing therapeutic and preventive measures. ",

author = "Noreen Mumtaz and Marijke Koedam and {van Leeuwen}, {Johannes P T M} and Koopmans, {Marion P G} and {van der Eerden}, {Bram C J} and Barry Rockx",

note = "Funding Information: This work was supported in part by ZonMW under grant number 522003001 (project: ZikaRisk “Risk of Zika virus introductions for the Netherlands”) and by the European Union{\textquoteright}s Horizon 2020 Research and Innovation Programme under grant number 734548 (project: ZIKAlliance). Publisher Copyright: {\textcopyright} 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd.",

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doi = "10.1080/22221751.2022.2086069",

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AU - Koedam, Marijke

AU - van Leeuwen, Johannes P T M

AU - Koopmans, Marion P G

AU - van der Eerden, Bram C J

AU - Rockx, Barry

N1 - Funding Information: This work was supported in part by ZonMW under grant number 522003001 (project: ZikaRisk “Risk of Zika virus introductions for the Netherlands”) and by the European Union’s Horizon 2020 Research and Innovation Programme under grant number 734548 (project: ZIKAlliance). Publisher Copyright: © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd.

PY - 2022/12

Y1 - 2022/12

N2 - Bone-related complications are commonly reported following arbovirus infection. These arboviruses are known to disturb bone-remodeling and induce inflammatory bone loss via increased activity of bone resorbing osteoclasts (OCs). We previously showed that Zika virus (ZIKV) could disturb the function of bone forming osteoblasts, but the susceptibility of OCs to ZIKV infection is not known. Here, we investigated the effect of ZIKV infection on osteoclastogenesis and report that infection of pre- and early OCs with ZIKV significantly reduced the osteoclast formation and bone resorption. Interestingly, infection of pre-OCs with a low dose ZIKV infection in the presence of flavivirus cross-reacting antibodies recapitulated the phenotype observed with a high viral dose, suggesting a role for antibody-dependent enhancement in ZIKV-associated bone pathology. In conclusion, we have characterized a primary in vitro model to study the role of osteoclastogenesis in ZIKV pathogenesis, which will help to identify possible new targets for developing therapeutic and preventive measures.

AB - Bone-related complications are commonly reported following arbovirus infection. These arboviruses are known to disturb bone-remodeling and induce inflammatory bone loss via increased activity of bone resorbing osteoclasts (OCs). We previously showed that Zika virus (ZIKV) could disturb the function of bone forming osteoblasts, but the susceptibility of OCs to ZIKV infection is not known. Here, we investigated the effect of ZIKV infection on osteoclastogenesis and report that infection of pre- and early OCs with ZIKV significantly reduced the osteoclast formation and bone resorption. Interestingly, infection of pre-OCs with a low dose ZIKV infection in the presence of flavivirus cross-reacting antibodies recapitulated the phenotype observed with a high viral dose, suggesting a role for antibody-dependent enhancement in ZIKV-associated bone pathology. In conclusion, we have characterized a primary in vitro model to study the role of osteoclastogenesis in ZIKV pathogenesis, which will help to identify possible new targets for developing therapeutic and preventive measures.

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Zika virus infects human osteoclasts and blocks differentiation and bone resorption

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