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Mechanistic insights into bone remodelling dysregulation by human viral pathogens

Nature Microbiology volume 9, pages 322–335 (2024)Cite this article

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Abstract

Bone-related diseases (osteopathologies) associated with human virus infections have increased around the globe. Recent findings have highlighted the intricate interplay between viral infection, the host immune system and the bone remodelling process. Viral infections can disrupt bone homeostasis, contributing to conditions such as arthritis and soft tissue calcifications. Osteopathologies can occur after arbovirus infections such as chikungunya virus, dengue virus and Zika virus, as well as respiratory viruses, such as severe acute respiratory syndrome coronavirus 2 and enteroviruses such as Coxsackievirus B. Here we explore how human viruses dysregulate bone homeostasis, detailing viral factors, molecular mechanisms, host immune response changes and bone remodelling that ultimately result in osteopathologies. We highlight model systems and technologies to advance mechanistic understanding of viral-mediated bone alterations. Finally, we propose potential prophylactic and therapeutic strategies, introduce ‘osteovirology’ as a research field highlighting the underestimated roles of viruses in bone-related diseases, and discuss research avenues for further investigation.

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Fig. 1: The cross-talk of bone remodelling.
Fig. 2: Pathogenic bone loss and calcifications.
Fig. 3: Inflammatory bone loss induced by arthritogenic alphaviruses.
Fig. 4: Mechanisms of ectopic calcification induced by ZIKV.

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Acknowledgements

W.C. was supported by grants R00DE028573 and R01DE033391 from the National Institute of Dental and Craniofacial Research.

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Author notes

  1. These authors contributed equally: Suan-Sin Foo, Weiqiang Chen.

Authors and Affiliations

  1. Infection Biology Program, Global Center for Pathogen Research and Human Health, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA

    Camila C. S. Caetano, Tamiris Azamor, Nikki M. Meyer, Chineme Onwubueke, Suan-Sin Foo & Weiqiang Chen

  2. Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, USA

    Chineme Onwubueke, Suan-Sin Foo & Weiqiang Chen

  3. Department of Rheumatic and Immunologic Diseases, Cleveland Clinic, Cleveland, OH, USA

    Cassandra M. Calabrese, Leonard H. Calabrese & M. Elaine Husni

  4. Department of Orthopedic Surgery, Cleveland Clinic, Cleveland, OH, USA

    Anabelle Visperas & Nicolas S. Piuzzi

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Contributions

W.C. and S.-S.F. contributed to the conceptualization of the manuscript. C.C.S.C., T.A., N.M.M., S.-S.F. and W.C. contributed to writing and revision of the manuscript. C.O., C.M.C., L.H.C., A.V., N.S.P. and M.E.H. contributed with additional text, ideas, edits and approval of the final manuscript.

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Correspondence to Suan-Sin Foo or Weiqiang Chen.

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Caetano, C.C.S., Azamor, T., Meyer, N.M. et al. Mechanistic insights into bone remodelling dysregulation by human viral pathogens. Nat Microbiol 9, 322–335 (2024). https://doi.org/10.1038/s41564-023-01586-6

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