Rubella Virus Strain-Associated Differences in the Induction of Oxidative Stress Are Independent of Their Interferon Activation

Zobel, Sarah; Lorenz, Mechthild; Frascaroli, Giada; Böhnke, Janik; Bilz, Nicole C.; Stanifer, Megan L.; Boulant, Steeve; Bergs, Sandra; Liebert, Uwe G.; Claus, Claudia

doi:10.3390/v10100540

Cited by 11 publications

(19 citation statements)

References 52 publications

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“…Those kinds of reactions are also activated by viral infections [5]. Virus-induced oxidative stress plays an important role in the regulation of the host immune system and the specific oxidant-sensitive pathway is one of the effective strategies against viral infections [6][7][8].…”

Section: Methodsmentioning

confidence: 99%

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Hydrogen peroxide and viral infections: A literature review with research hypothesis definition in relation to the current covid-19 pandemic

Caruso

Prete

Lazzarino³

2020

Medical Hypotheses

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We reviewed the literature concerning the innate response from nasal and oral epithelial cells and their reaction to hydrogen peroxide (H 2 O 2 ). Hydrogen peroxide is produced physiologically by oral bacteria and plays a significant role in the balance of oral microecology since it is an important antimicrobial agent. In the epithelial cells, the enzyme superoxide dismutase catalyzes a reaction leading from hydrogen peroxide to the ion superoxide. The induced oxidative stress stimulates a local innate response via activation of the toll-like receptors and the NF-κB. Those kinds of reactions are also activated by viral infections. Virus-induced oxidative stress plays an important role in the regulation of the host immune system and the specific oxidant-sensitive pathway is one of the effective strategies against viral infections. Therefore, nose/mouth/throat washing with hydrogen peroxide may enhance those local innate responses to viral infections and help protect against the current coronavirus pandemic. We strongly encourage the rapid development of randomized controlled trials in both SARS-CoV-2 positive and negative subjects to test the preliminary findings from the in-vitro and in-vivo observational studies that we identified.

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Section: Methodsmentioning

confidence: 99%

“…Many viruses have been found to be sensitive to hydrogen peroxide, including swine flu, rubella, rabies, and others [7,[9][10][11][12][13][14][15][16][17][18][19][20][21].…”

Section: Methodsmentioning

confidence: 99%

Hydrogen peroxide and viral infections: A literature review with research hypothesis definition in relation to the current covid-19 pandemic

Caruso

Prete

Lazzarino³

2020

Medical Hypotheses

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“…In contrast to HCMV and ZIKV, RV displays only a low level of variation within its low-passaged clinical isolates. While differences in the adaptation of cellular metabolism and the requirement for glutamine were detected [56], a comparable level of innate immune activation was identified [22]. Moreover, the number of circulating RV strains has decreased in the last decade.…”

Section: Implications Of Genetic Variations Of Teratogenic Virusesmentioning

confidence: 98%

“…Infection after the last menstrual period and before conception does not lead to congenital defects, whereas the first 11 weeks postconception are critical [11,12]. During viremia, lymphocytes or macrophages can either be infected and support virus replication or harbor the virus [15,21,22], which, as a hypothesis, could enable viral transfer to the hemochorial placenta. While first-trimester trophoblast cells were reported to be resistant to RV infection [23], explants of chorionic villi from human placentas and primary CTBs were susceptible [24].…”

Section: All Congenital Viral Infections Face An Efficient Barrier: Tmentioning

confidence: 99%

Pluripotent Stem Cell-Based Models: A Peephole into Virus Infections during Early Pregnancy

Claus

Jung

Hübschen

2020

Cells

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The rubella virus (RV) was the first virus shown to be teratogenic in humans. The wealth of data on the clinical symptoms associated with congenital rubella syndrome is in stark contrast to an incomplete understanding of the forces leading to the teratogenic alterations in humans. This applies not only to RV, but also to congenital viral infections in general and includes (1) the mode of vertical transmission, even at early gestation, (2) the possible involvement of inflammation as a consequence of an activated innate immune response, and (3) the underlying molecular and cellular alterations. With the progress made in the development of pluripotent stem cell-based models including organoids and embryoids, it is now possible to assess congenital virus infections on a mechanistic level. Moreover, antiviral treatment options can be validated, and newly emerging viruses with a potential impact on human embryonal development, such as that recently reflected by the Zika virus (ZIKV), can be characterized. Here, we discuss human cytomegalovirus (HCMV) and ZIKV in comparison to RV as viruses with well-known congenital pathologies and highlight their analysis on current models for the early phase of human development. This includes the implications of their genetic variability and, as such, virus strain-specific properties for their use as archetype models for congenital virus infections. In this review, we will discuss the use of induced pluripotent stem cells (iPSC) and derived organoid systems for the study of congenital virus infections with a focus on their prominent aetiologies, HCMV, ZIKV, and RV. Their assessment on these models will provide valuable information on how human development is impaired by virus infections; it will also add new insights into the normal progression of human development through the analysis of developmental pathways in the context of virus-induced alterations. These are exciting perspectives for both developmental biology and congenital virology.

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“…It is especially noteworthy, that RV can replicate in both human MΦ types ( 11 ) thus allowing a direct comparison of virus infection-associated changes in the two subsets.…”

Section: Introductionmentioning

confidence: 99%

The Impact of Rubella Virus Infection on a Secondary Inflammatory Response in Polarized Human Macrophages

et al. 2021

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Macrophages (MΦ) are known to exhibit distinct responses to viral and bacterial infection, but how they react when exposed to the pathogens in succession is less well understood. Accordingly, we determined the effect of a rubella virus (RV)-induced infection followed by an LPS-induced challenge on cytokine production, signal transduction and metabolic pathways in human GM (M1-like)- and M (M2-like)-MΦ. We found that infection of both subsets with RV resulted in a low TNF-α and a high interferon (IFN, type I and type III) release whereby M-MΦ produced far more IFNs than GM-MΦ. Thus, TNF-α production in contrast to IFN production is not a dominant feature of RV infection in these cells. Upon addition of LPS to RV-infected MΦ compared to the addition of LPS to the uninfected cells the TNF-α response only slightly increased, whereas the IFN-response of both subtypes was greatly enhanced. The subset specific cytokine expression pattern remained unchanged under these assay conditions. The priming effect of RV was also observed when replacing RV by IFN-β one putative priming stimulus induced by RV. Small amounts of IFN-β were sufficient for phosphorylation of Stat1 and to induce IFN-production in response to LPS. Analysis of signal transduction pathways activated by successive exposure of MΦ to RV and LPS revealed an increased phosphorylation of NFκB (M-MΦ), but different to uninfected MΦ a reduced phosphorylation of ERK1/2 (both subtypes). Furthermore, metabolic pathways were affected; the LPS-induced increase in glycolysis was dampened in both subtypes after RV infection. In conclusion, we show that RV infection and exogenously added IFN-β can prime MΦ to produce high amounts of IFNs in response to LPS and that changes in glycolysis and signal transduction are associated with the priming effect. These findings will help to understand to what extent MΦ defense to viral infection is modulated by a following exposure to a bacterial infection.

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Rubella Virus Strain-Associated Differences in the Induction of Oxidative Stress Are Independent of Their Interferon Activation

Cited by 11 publications

References 52 publications

Hydrogen peroxide and viral infections: A literature review with research hypothesis definition in relation to the current covid-19 pandemic

Hydrogen peroxide and viral infections: A literature review with research hypothesis definition in relation to the current covid-19 pandemic

Pluripotent Stem Cell-Based Models: A Peephole into Virus Infections during Early Pregnancy

The Impact of Rubella Virus Infection on a Secondary Inflammatory Response in Polarized Human Macrophages

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