Zika virus infects human osteoclasts and blocks differentiation and bone resorption

Mumtaz, Noreen; Koedam, Marijke; Leeuwen, Johannes P. T. M. van; Eerden, Bram C.J. van der; Rockx, Barry

doi:10.1080/22221751.2022.2086069

Cited by 6 publications

(5 citation statements)

References 64 publications

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“…One of the top three affected pathways in fetal and offspring bone marrow cells was “osteoclast differentiation” ( Table S1-B and D ). Interestingly, it has been recently shown that ZIKV infection can affect osteoclast and osteoblast functions [ 28 , 29 ]. In addition to commonly affected proteins in fetuses and offspring, we also identified proteins uniquely affected in ZIKV offspring that were related to hematopoiesis (13 proteins) and bone marrow cancer (3 proteins) ( Figure 4 ; references are in File S1 ).…”

Section: Resultsmentioning

confidence: 99%

Offspring affected with in utero Zika virus infection retain molecular footprints in the bone marrow and blood cells

Udenze

Trus

Lipsit

et al. 2023

Emerging Microbes & Infections

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Congenital virus infections, for example cytomegalovirus and rubella virus infections, commonly affect the central nervous and hematological systems in fetuses and offspring. However, interactions between emerging congenital Zika virus and hematological system—bone marrow and blood—in fetuses and offspring are mainly unknown. Our overall goal was to determine whether silent in utero Zika virus infection can cause functional and molecular footprints in the bone marrow and blood of fetuses and offspring. We specifically focused on silent fetal infection because delayed health complications in initially asymptomatic offspring were previously demonstrated in animal and human studies. Using a well-established porcine model for Zika virus infection and a set of cellular and molecular experimental tools, we showed that silent in utero infection causes multi-organ inflammation in fetuses and local inflammation in the fetal bone marrow. In utero infection also caused footprints in the offspring bone marrow and PBMCs. These findings should be considered in a broader clinical context because of growing concerns about health sequelae in cohorts of children affected with congenital Zika virus infection in the Americas. Understanding virus-induced molecular mechanisms of immune activation and inflammation in fetuses may provide targets for early in utero interventions. Also, identifying early biomarkers of in utero -acquired immunopathology in offspring may help to alleviate long-term sequelae.

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Section: Resultsmentioning

confidence: 99%

Offspring affected with in utero Zika virus infection retain molecular footprints in the bone marrow and blood cells

Udenze

Trus

Lipsit

et al. 2023

Emerging Microbes & Infections

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“…45 Kellie A. Jurado et al 46 show that an increased number of Foxp3+ regulatory T cells were found in ZIKV-infected compared to mock-infected IFNAR1 −/− mice, further illustrating the importance of adaptive immunity in the ZIKV response. A recent study by Noreen Mumtaz et al 47 show that ZIKV infection disrupts osteoclast differentiation and function, and speculated that ZIKV-associated microcephaly may be involved. Claudia P. Figueiredo et al 36 report that ZIKV replication and TNF-α upregulation in adult brain tissue may induce synaptic and memory dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic reveals the ferroptosis features of host response in a mouse model of Zika virus infection

Yan

Zheng

Jiang

et al. 2022

Journal of Medical Virology

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Zika virus (ZIKV) is a neurotropic flavivirus. The outbreak of ZIKV in 2016 created a global health emergency. However, the underlying pathogenic mechanisms remain elusive. We investigated the host response features of in vivo replication in a mouse model of ZIKV infection, by performing a series of transcriptomic and bioinformatic analyses of ZIKV and mock‐infected brain tissue. Tissue damage, inflammatory cells infiltration and high viral replication were observed in the brain tissue of ZIKV infected mice. RNA‐Seq of the brain indicated the activation of ferroptosis pathways. Enrichment analysis of ferroptosis regulators revealed their involvement in pathways such as mineral absorption, fatty acid biosynthesis, fatty acid degradation, PPAR signaling pathway, peroxidase, and adipokinesine signalling pathway. We then identified 12 interacted hub ferroptosis regulators (CYBB, HMOX1, CP, SAT1, TF, SLC39A14, FTL, LPCAT3, FTH1, SLC3A2, TP53, and SLC40A1) that were related to the differential expression of CD8+ T cells, microglia and monocytes. CYBB, HMOX1, SALT, and SLAC40A1 were selected as potential biomarkers of ZIKV infection. Finally, we validated our results using RT‐qPCR and outside available datasets. For the first time, we proposed a possible mechanism of ferroptosis in brain tissue infected by ZIKV in mice and identified the four key ferroptosis regulators.

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“…In the case of HIV infection, bone resorption is promoted, with the extent influenced by the infection load 15,16 . On the other hand, Zika virus infection impedes bone remodeling in OC 17 . Research utilizing animal models suggests that SARS‐CoV‐2 affects bone metabolism both during acute infection and in the postrecovery phases 18–20 …”

Section: Introductionmentioning

confidence: 99%

“…15,16 On the other hand, Zika virus infection impedes bone remodeling in OC. 17 Research utilizing animal models suggests that SARS-CoV-2 affects bone metabolism both during acute infection and in the postrecovery phases. [18][19][20] This study examines the direct effects of SARS-CoV-2 on osteoclastogenesis, maturation, and resorption activity using osteoclast precursors from human peripheral blood mononuclear cells (PBMCs).…”

mentioning

confidence: 99%

The abortive SARS‐CoV‐2 infection of osteoclast precursors promotes their differentiation into osteoclasts

Sviercz,

Jarmoluk,

Godoy Coto

et al. 2024

Journal of Medical Virology

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The Coronavirus Disease 2019 (COVID‐19) pandemic has resulted in the loss of millions of lives, although a majority of those infected have managed to survive. Consequently, a set of outcomes, identified as long COVID, is now emerging. While the primary target of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is the respiratory system, the impact of COVID‐19 extends to various body parts, including the bone. This study aims to investigate the effects of acute SARS‐CoV‐2 infection on osteoclastogenesis, utilizing both ancestral and Omicron viral strains. Monocyte‐derived macrophages, which serve as precursors to osteoclasts, were exposed to both viral variants. However, the infection proved abortive, even though ACE2 receptor expression increased postinfection, with no significant impact on cellular viability and redox balance. Both SARS‐CoV‐2 strains heightened osteoclast formation in a dose‐dependent manner, as well as CD51/61 expression and bone resorptive ability. Notably, SARS‐CoV‐2 induced early pro‐inflammatory M1 macrophage polarization, shifting toward an M2‐like profile. Osteoclastogenesis‐related genes (RANK, NFATc1, DC‐STAMP, MMP9) were upregulated, and surprisingly, SARS‐CoV‐2 variants promoted RANKL‐independent osteoclast formation. This thorough investigation illuminates the intricate interplay between SARS‐CoV‐2 and osteoclast precursors, suggesting potential implications for bone homeostasis and opening new avenues for therapeutic exploration in COVID‐19.

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Zika virus infects human osteoclasts and blocks differentiation and bone resorption

Cited by 6 publications

References 64 publications

Offspring affected with in utero Zika virus infection retain molecular footprints in the bone marrow and blood cells

Offspring affected with in utero Zika virus infection retain molecular footprints in the bone marrow and blood cells

Transcriptomic reveals the ferroptosis features of host response in a mouse model of Zika virus infection

The abortive SARS‐CoV‐2 infection of osteoclast precursors promotes their differentiation into osteoclasts

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