Zika virus infection leads to mitochondrial failure, oxidative stress and DNA damage in human iPSC-derived astrocytes

Ledur, Pítia Flores; Karmirian, Karina; Pedrosa, Carolina da S. G.; Souza, Letícia R. Q.; Assis-de-Lemos, Gabriela; Martins, Thiago Martino; Ferreira, Jéssica de Cassia Cavalheiro Gomes; Reis, Gabriel Ferreira de Azevedo; Silva, Eduardo Santos; Silva, Débora; Salerno, José Alexandre; Ornelas, Isis M.; Devalle, Sylvie; Costa, Rosa Maria Esteves Moreira da; Goto‐Silva, Livia; Higa, Luiza M.; Melo, Adriana; Tanuri, Amílcar; Chimelli, Leila; Murata, Marcos Massao; Garcez, Patrícia P.; Filippi-Chiela, Eduardo Cremonese; Galina, Antônio; Borges, Helena L.; Rehen, Stevens K.

doi:10.1038/s41598-020-57914-x

Cited by 101 publications

(109 citation statements)

References 82 publications

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“…Once the integrity of BBB, which is composed of specialized microvascular endothelial cells, is crossed, the virus is able to reach and infect its target cells, and thus, presentation of rare clinical events may be observed [107]. Indeed, a number of studies have shown the prominent role of astrocytes in ZIKV infection [108][109][110][111][112], which may play a role in ZIKV infection in the brain.…”

Section: Discussionmentioning

confidence: 99%

Flavivirus Infection Associated with Cerebrovascular Events

Estofolete

Milhim

Zini

et al. 2020

Viruses

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Arthropod-borne viruses (arboviruses) of the genus Flavivirus are distributed globally and cause significant human disease and mortality annually. Flavivirus infections present a spectrum of clinical manifestations, ranging from asymptomatic to severe manifestations, including hemorrhage, encephalitis and death. Herein, we describe 3 case reports of cerebrovascular involvement in patients infected by dengue and Zika viruses in Sao Jose do Rio Preto, São Paulo State, Brazil, a hyperendemic area for arbovirus circulation, including dengue, yellow fever, chikungunya and Saint Louis encephalitis viruses. Our findings highlight the potential threat that unusual clinical manifestations may pose to arbovirus disease management and recovery.

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Section: Discussionmentioning

confidence: 99%

Flavivirus Infection Associated with Cerebrovascular Events

Estofolete

Milhim

Zini

et al. 2020

Viruses

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“…This dysregulation has been previously observed during placental transcriptome profiling 29 and may be related to an overall cellular energy imbalance induced by ZIKV infection. 54 In summary, we conclude that ZIKV differs from other flaviviruses in downregulating IGF2 gene expression, although further studies are necessary to investigate the mechanisms involved. We also showed that mutations in the ZIKV genome may result in differences in the biology of the viruses and, consequently, the host response.…”

Section: Discussionmentioning

confidence: 72%

Downregulation of IGF2 expression in third trimester placental tissues from Zika virus infected women in Brazil

Suzukawa

Zanluca

Jorge³

et al. 2020

Journal of Infection

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Objectives: Screening for genes differentially expressed in placental tissues, aiming to identify transcriptional signatures that may be involved in ZIKV congenital pathogenesis. Methods: Transcriptome data from placental tissues of pregnant women naturally infected with Zika virus during the third trimester were compared to those from women who tested negative for Zika infection. The findings were validated using both a cell culture model and an immunohistochemistry/morphological analysis of naturally infected placental tissues. Results: Transcriptome analysis revealed that Zika virus infection induces downregulation of insulin-like growth factor II (IGF2) gene, an essential factor for fetal development. The Caco-2 cell culture model that constitutively expresses IGF2 was used for the transcriptome validation. Asiatic and African Zika virus strains infection caused downregulated IGF2 gene expression in Caco-2 cells, whereas other flaviviruses, such as dengue serotype 1, West Nile and wild-type yellow fever viruses, had no effect on this gene expression. Immunohistochemical assays on decidual tissues corroborated our transcriptome analysis, showing that IGF2 is reduced in the decidua of Zika virus-infected women. Conclusions: Our results draw attention to IGF2 modulation in uterine tissues, and this finding is expected to support future studies on strategies to ameliorate the harmful effects of Zika virus infection during pregnancy.

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“…Accordingly, it has been speculated that blood pressure elevation might result in development of hypertension [23]. Furthermore, it is known that DNA undergoes oxidative damage from oxidant stress [24,25], while others have shown that tetradecanoyl phorbol (TPA), a carcinogen formed by DNA damage, induces activation of breast cancer cells [26][27][28]. Therefore, it is likely that an increased concentration of active oxygen might impair mammary gland cells, leading to onset of mammary gland disease.…”

Section: Discussionmentioning

confidence: 99%

Analysis of metabolic syndrome factors to determine contributions to pathogenesis of mammary gland disease in Japanese women– Case-control study based on health screening results

Iida¹,

Sumida²,

Yoshikawa³

et al. 2020

Preprint

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Background: Recently, the relationship between obesity and breast cancer has been clarified, and findings obtained in a study that used body mass index (BMI) suggested that its presence might increase the risk for development of that disease. However, the association between metabolic syndrome caused by obesity and development of mammary gland disease has not been elucidated in a longitudinal manner. In the present case-control study, that association was examined.Methods: Two hundred sixty-five women who underwent breast cancer screening with mammography and measurements of metabolic syndrome factors, including waist circumference, blood glucose, and triglycerides, HDL-cholesterol levels, and systolic and diastolic blood pressure, twice within a 2-year period at the Disease Prevention Promotion and Research Center of the Dai-ikai Medical Corporation were enrolled. To determine the presence of mammary gland disease, 2 expert physicians interpreted radiogram findings, with category 3 or higher shown by mammography considered to indicate an abnormality.Results and Discussion: Waist circumference at the initial measurement was shown to be significantly associated (odds ratio=1.036, p=0.045) as a risk factor for onset of mammary gland disease. During the 2-year examination period, changes in systolic blood pressure (odds ratio=1.020, p=0.085) and diastolic pressure (odds ratio=1.040, p=0.065) showed a marginally significant association. As for protective factors, HDL-cholesterol level (odds ratio=0.982, p=0.064) at the initial examination was confirmed to have a marginally significant relationship. We concluded that waist circumference and 2-year changes in systolic and diastolic blood pressure are risk factors for mammary gland disease, while HDL-cholesterol level is a protective factor.

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Zika virus infection leads to mitochondrial failure, oxidative stress and DNA damage in human iPSC-derived astrocytes

Cited by 101 publications

References 82 publications

Flavivirus Infection Associated with Cerebrovascular Events

Flavivirus Infection Associated with Cerebrovascular Events

Downregulation of IGF2 expression in third trimester placental tissues from Zika virus infected women in Brazil

Analysis of metabolic syndrome factors to determine contributions to pathogenesis of mammary gland disease in Japanese women– Case-control study based on health screening results

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