Human Osteoblast-like Cells Are Permissive for Zika Virus Replication

Colavita, Francesca; Musumeci, Giuseppina; Caglioti, Claudia

doi:10.3899/jrheum.170835

Cited by 7 publications

(4 citation statements)

References 11 publications

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“…ZIKV readily infects differentiating primary human osteoblasts and grows to high titers within 2 days post infection. These findings are in line with a recent report which confirms the susceptibility of a human osteoblast-like cell line (HOBIT) to ZIKV 11 , as well as observations from other arthritogenic arboviruses such as CHIKV 17 . However, in contrast to previous studies we did not observe CPE in ZIKV-infected primary osteoblasts.…”

Section: Discussionsupporting

confidence: 92%

“…ZIKV has been detected in synovial fluid of a patient with arthralgia 10 , and a recent study has shown the susceptibility of an osteoblast-like cell line for ZIKV infection 11 . Osteoblasts originate from mesenchymal stem cells (MSCs) and in a recent case of miscarriage associated with ZIKV infection, ZIKV displayed tropism for fetal MSC in the perichondrium 12 .…”

Section: Introductionmentioning

confidence: 99%

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Zika virus infection perturbs osteoblast function

Mumtaz

Koedam

Doel

et al. 2018

Sci Rep

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Zika virus (ZIKV) infection is typically characterized by a mild self-limiting disease presenting with fever, rash, myalgia and arthralgia and severe fetal complications during pregnancy such as microcephaly, subcortical calcifications and arthrogyropsis. Virus-induced arthralgia due to perturbed osteoblast function has been described for other arboviruses. In case of ZIKV infection, the role of osteoblasts in ZIKV pathogenesis and bone related pathology remains unknown. Here, we study the effect of ZIKV infection on osteoblast differentiation, maturation and function by quantifying activity and gene expression of key biomarkers, using human bone marrow-derived mesenchymal stromal cells (MSCs, osteoblast precursors). MSCs were induced to differentiate into osteoblasts and we found that osteoblasts were highly susceptible to ZIKV infection. While infection did not cause a cytopathic effect, a significant reduction of key osteogenic markers such as ALP, RUNX2, calcium contents and increased expression of IL6 in ZIKV-infected MSCs implicated a delay in osteoblast development and maturation, as compared to uninfected controls. In conclusion, we have developed and characterized a new in vitro model to study the role of bone development in ZIKV pathogenesis, which will help to identify possible new targets for developing therapeutic and preventive measures.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Zika virus infection perturbs osteoblast function

Mumtaz

Koedam

Doel

et al. 2018

Sci Rep

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“…Indeed, the viral nonstructural protein 2 (nsP2) has been shown to inhibit IFN stimulated JAK-STAT signaling [117], and the nonstructural protein 1 (nsP1) contrast viral restriction mediated by the IFN stimulated gene product BST-2/Tetherin [118]. Whether IFN-type-I overproduction may result in the exacerbation of clinical symptoms, as suggested in a case report [119], should be further investigated.…”

Section: Human Infectionmentioning

confidence: 99%

Tropism of the Chikungunya Virus

Matusali

Colavita

Bordi

et al. 2019

Viruses

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Chikungunya virus (CHIKV) is a re-emerging mosquito-borne virus that displays a large cell and organ tropism, and causes a broad range of clinical symptoms in humans. It is maintained in nature through both urban and sylvatic cycles, involving mosquito vectors and human or vertebrate animal hosts. Although CHIKV was first isolated in 1953, its pathogenesis was only more extensively studied after its re-emergence in 2004. The unexpected spread of CHIKV to novel tropical and non-tropical areas, in some instances driven by newly competent vectors, evidenced the vulnerability of new territories to this infectious agent and its associated diseases. The comprehension of the exact CHIKV target cells and organs, mechanisms of pathogenesis, and spectrum of both competitive vectors and animal hosts is pivotal for the design of effective therapeutic strategies, vector control measures, and eradication actions.

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“…Another cell lineage to which ZIKV has demonstrated tropism is osteoblast cells by disturbing their differentiation, maturation, and function. 3 The presence of ZIKV on synovial fluid correlates with the development of arthralgias in primary infection, 17 but the imbalance in bone homeostasis is due to impaired osteoblast function, which can induce bone-related disorders while the fetus is developing. 1 Arthrogryposis, one of the most limiting extracranial conditions, involves multiple joint contractures, and its association with CZS has been described with flexed wrists as the most common finding.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Multiorgan Involvement with Congenital Zika Syndrome

Cachay

Schwalb

Watanabe

et al. 2020

The American Journal of Tropical Medicine and Hygiene

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We report the case of an infant born with congenital Zika syndrome (CZS). During the largest Zika virus (ZIKV) outbreak in Peru, the mother presented with fever and rash that were confirmed to be due to ZIKV by real-time PCR. The infant was born with severe microcephaly. Imaging revealed corpus callosum dysgenesis, lissencephaly, ventriculomegaly, and calcifications. Mild hypertrophic cardiomyopathy with diastolic dysfunction was reported in the echocardiogram. Valgus deviation of the lower extremities and a left clubfoot were diagnosed at birth. The hip ultrasound showed incipient signs of Graf type II dysplasia. The findings confirm that CZS is a multiorgan phenotype in which microcephaly is merely the tip of the iceberg. A multidisciplinary approach is needed for the evaluation of these children.

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Human Osteoblast-like Cells Are Permissive for Zika Virus Replication

Cited by 7 publications

References 11 publications

Zika virus infection perturbs osteoblast function

Zika virus infection perturbs osteoblast function

Tropism of the Chikungunya Virus

Case Report: Multiorgan Involvement with Congenital Zika Syndrome

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