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We analyzed the role of the MEKV gene and the effects of the MEK inhibitor trametinib on the Asian ZIKV strain PE243 and the prototype African ZIKV strain MR766, focusing on genome replication, morphogenesis, and viral release in this research. At 12 and 18 hours postinfection, ZIKV infection stimulated ERK phosphorylation in Vero cells. Trametinib had sustained antiviral activity, inhibiting both ZIKV strains for at least four days, and electron microscopy revealed probable inhibition of ZIKV morphogenesis. ZIKV PE243 can complete one cycle in Vero cells in 14 hours; genome replication is found around 8 hpi, intracellular viral particles at 12 hpi, and extracellular progeny at 14 hpi; genome replication is estimated around 8 hpi, extracellular progeny, and extracellular progeny at 14 hpi. Thus, ZIKV stimulated ERK phosphorylation during viral propagation and release, which was linked to trametinib-inhibition of both the signaling pathway and viral replication.
Source link: https://europepmc.org/article/MED/36609616
During the 2015/16 Zika virus outbreak, ZIKV-associated neurological disorders were recorded in adults, including microcephaly, Guillain-Barre syndrome, myelitis, meningoencephalitis, and deadly encephalitis. However, the mechanisms behind ZIKV infection's neuropathogenesis are not fully understood. Genes involved in innate immune responses and cytokine-mediated signaling pathways were also highly upregulated 6 days after infection, according to RNA-seq analysis of the infected mouse brain, which also revealed that genes involved in innate immune responses and cytokine-mediated signaling pathways were significantly elevated 6 days after infection. We discovered that ZIKV infection promotes inflammatory cell death and raises IL-1u03b2 secretion by using human monocyte THP-1 cells. An increase in C5a produced by complement activation in the brains of ZIKV-infected mice was also reported. Our findings show that ZIKV infection of the brain in this animal model increases IL-1u03b2 expression in infiltrating macrophages and elicits IL-1u03b2-mediated inflammation, which may lead to neuroinflammation's destructive effects.
Source link: https://europepmc.org/article/PPR/PPR593459
Zika virus infects fetal neural progenitor cells, causing severe neurodevelopmental disorders in infants. Infected NPCs, the pathways involved in normal brain development are dysfunctional, but how ZIKV centrally reprograms pathways is unknown. Here we demonstrate that ZIKV infection disrupts subcellular partitioning of host transcripts essential for neurodevelopment in NPCs, and we can connect this process to the up-frameshift protein 1. Our findings connect UPF1 to the regulation of mRNA transport in NPCs, a process that was interrupted during ZIKV infection.
Source link: https://europepmc.org/article/MED/36603024
Monocytes are considered the first blood cell type to be infected by ZIKV and have been shown to be associated with ZIKV pathogenesis. The first ZIKV epidemic was recorded in Africa and Asia, but it is not well known if African- and Asian-lineages of ZIKV have differing effects on host immune response. According to the transcriptomic review, ZIKV Puerto Rico strain promotes a higher pro-inflammatory response through TLR2 signaling and NF-kB activation, which also leads to increased IL27-dependent antiviral activity than ZIKV N. . . . ia strain. In addition, human monocytes are more susceptible to ZIKV from Colombia than ZIKV from Dakar. Moreover, we show that with an EC50 =10. 23 ng/mL from Dakar, we show that IL27 therapy of monocytes resulted in reduced release of ZIKV particles in a dose-dependent manner, with a EC50 = 10. 23 ng/mL.
Source link: https://europepmc.org/article/MED/36610657
The lack of details about ZIKV interactions with host cells in the early stages of disease in the early stages of infection has hampered in the prevention of viral outbreaks and ZIKV disease treatment. This research establishes the dual roles of mTOR signaling during ZIKV disease and provides theoretical support for the development of potential anti-ZIKV drugs based on mTOR signaling molecules as well as deeper insight into the mechanism between ZIKV and host cells.
Source link: https://europepmc.org/article/MED/36546404
Zika virus is a neurotropic flavivirus. By conducting a series of transcriptomic and bioinformatic analyses of ZIKV and mock-infected brain tissue, we investigated the host response characteristics of in vivo replication in a mouse model of ZIKV infection in a mouse model of ZIKV infection. We later identified 12 interacted hub ferroptosis regulators that were related to the difference in the expression of CD8+ T cells, microglia, and monocytes. For the first time, we proposed a potential mechanism of ferroptosis in brain tissue infected by ZIKV in mice and outlined the four key ferroptosis regulators.
Source link: https://europepmc.org/article/MED/36477858
Although nearly 80% of ZIKV infections are asymptomatic and mild, several studies have established a correlation between ZIKV and common diseases such as Microcephaly and Guillain Barru00e9 Syndrome. This study aims to develop ZIKV models by investigating the transmission dynamics of ZIKV, both a vector-borne and sexually transmitted disease epidemic as well as estimating the risk of under-reporting. We find that focusing the sexual pathway alone has negligible effect on overall spread, but if the number of risky sexual activities increases, it could become significant. The findings may be helpful to public health agencies and governments in developing and implementing appropriate health programs and minimizing the Zika outbreaks' impact.
Source link: https://europepmc.org/article/MED/36584063
Zika virus is a Flaviviridae virus and a single strand RNA virus with a positive-sense single strand RNA virus. This review article summarizes the most recent findings on ZIKV transmission and diagnosis, as well as reviews nutraceuticals that can shield against the ZIKV virus. Further, we have reviewed recent developments related to the novel therapeutic nutrient molecules that have been shown to have activity against Zika virus infected cells. We also discuss the development of ZIKV-induced endoplasmic reticulum and apoptosis, as well as the protective role of palmitoleate against ZIKV-induced ER stress and apoptosis in the placental trophoblasts.
Source link: https://europepmc.org/article/MED/36615782
Background The United States Virgin Islands Department of Health conducted a second Zika health brigade in 2021 to provide recommended Zika-related pediatric health screenings, including vision, hearing, neurologic, and developmental screenings for children in the USVI. This was replicated after the first ZHB's success in 2018, which provided recommended Zika-related pediatric health screenings to 88 infants and children exposed to Zika virus during pregnancy. Results Thirty-three children born to mothers with laboratory evidence of ZIKV infection during pregnancy completed screenings at the 2021 ZHB, of which 15 children were referred to additional follow-up care. At the ZHB, three children in a jurisdiction with reduced access to healthcare professionals were screened for Zika-related pediatric health screenings. The ZHB scheme was a success in establishing links to health services that had not previously been available to participants.
Source link: https://europepmc.org/article/MED/36574736
Background Zika virus, fetal microcephaly, and Guillain-Barru00e9 syndrome among the population are all common causes of congenital infection, fetal microcephaly, and Guillain-Barru00e9 syndrome. WHO reported a cluster of microcephaly cases and other neurological disorders in Brazil in 2016 as a global public health emergency. Zika virus fever is not yet approved by any medical device, only palliative care. According to the literature, thiosemicarbazone, phthalimide, and thiazole are favored structures for numerous biological functions, including antiviral activity against various viruses. Objects This work focuses on this and aims to conduct an antiviral screening using previously synthesized compounds derived from thiosemicarbazone, phthalimide, and thiazole as new ZIKV's latest hits on ZIKV. Methods Following the synthesis and analysis, all compounds were tested for Cytotoxicity by MTT and Antiviral activity against ZIKV assays. At the CC20 dose, 63, 64, 65, and 73 had a higher inhibition than the normal 6MMPr. These findings revealed novel chemical entities with anti-ZikV activity.
Source link: https://europepmc.org/article/MED/36567284
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