ArticleEmerging microbes & infections2019
Exosomes mediate Zika virus transmission through SMPD3 neutral Sphingomyelinase in cortical neurons.
Article in Emerging microbes & infections, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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Who cites it
94 citing papers in PubMed, 121 citations in OpenAlex.
- Beyond spherical vesicles: morphological diversity of extracellular vesicles in health and disease.Annals of medicine · 2026Review
- Ligand‑Based Virtual Screening Discovery of Thienopyrimidinone Derivatives as Allosteric nSMase2 Modulators and Antivirals Against West Nile Virus.ChemMedChem · 2026Article
- Exosomes mediate intercellular transmission of Tembusu virus via the NS4A-Rab27a axis.Veterinary research · 2026Article
- The K247 ubiquitination site of the Newcastle disease virus M protein enhances viral budding to facilitate rapid exploitation of host cell sphingolipid metabolites.Poultry science · 2026Article
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- Zika virus: unraveling the complex interplay between viral pathogenesis and host immune defenses.Virology journal · 2026Review
- hTERT-immortalized mesenchymal stem cell-derived EV treatment reduces ZIKV-induced cortical neuronal death, infection, and exosome-mediated transmission.Microbiology spectrum · 2026Article
- Lipidomics reveals the pro-viral roles of ceramides during fish nodavirus infection.Journal of virology · 2026Article
- Arthropod exosomal glycine-rich protein as a potential vaccine candidate effectively reduces tick blood-feeding and pathogen transmission.The EMBO journal · 2026Article
- Persistent and Long-Term Infectivity of Dengue Virus in Mosquito Cells Revealed Reduced Replication in Vector Host and Human Endothelial Cells.Pathogens (Basel, Switzerland) · 2026Article
- Interactions between extracellular vesicles and viruses: lessons learned across species and kingdoms.FEMS microbiology reviews · 2026Review
- Zika virus infection induces ultrastructural alterations, mitochondrial dysfunction and oxidative stress in human trophoblast HTR-8/SVneo.Frontiers in cellular and infection microbiology · 2026Article
- Extracellular vesicles in viral disease management.Current research in microbial sciences · 2026Review
- Comparative analysis of placental transmission mechanisms for Dengue and Zika viruses: outcomes and future directions.Frontiers in immunology · 2026Review
- Zika Virus Infection Is More Highly Replicative and Transmissible by Extracellular Vesicles in Human than in Mouse Neuronal Cells.International journal of molecular sciences · 2025Article
- Lipids, Tetraspanins, and Exosomes: Cell Factors inViruses · 2025Review
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- Ultrastructural Insight into Rift Valley Fever Virus Pathogenesis in Different Human Cell Types.International journal of molecular sciences · 2025Article
- NCancer communications (London, England) · 2025Article
- Mosquito Exosomal Tetraspanin CD151 Facilitates Flaviviral Transmission and Interacts with ZIKV and DENV2 Viral Proteins.International journal of molecular sciences · 2025Article
34 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The harmful effects of ZIKA virus (ZIKV) infection are reflected by severe neurological manifestations such as microcephaly in neonates and other complications associated with Guillain-Barré syndrome in adults. The transmission dynamics of ZIKV in or between neurons, or within the developing brains of the foetuses are not fully understood. Using primary cultures of murine cortical neurons, we show that ZIKV uses exosomes as mediators of viral transmission between neurons. Cryo-electron microscopy showed heterogeneous population of neuronal exosomes with a size range of 30-200 nm. Increased production of exosomes from neuronal cells was noted upon ZIKV infection. Neuronal exosomes contained both ZIKV viral RNA and protein(s) that were highly infectious to naïve cells. RNaseA and neutralizing antibodies treatment studies suggest the presence of viral RNA/proteins inside exosomes. Exosomes derived from time- and dose-dependent incubations showed increasing viral loads suggesting higher packaging and delivery of ZIKV RNA and proteins. Furthermore, we noted that ZIKV induced both activity and gene expression of neutral Sphingomyelinase (nSMase)-2/SMPD3, an important molecule that regulates production and release of exosomes. Silencing of SMPD3 in neurons resulted in reduced viral burden and transmission through exosomes. Treatment with SMPD3 specific inhibitor GW4869, significantly reduced ZIKV loads in both cortical neurons and in exosomes derived from these neuronal cells. Taken together, our results suggest that ZIKV modulates SMPD3 activity in cortical neurons for its infection and transmission through exosomes perhaps leading to severe neuronal death that may result in neurological manifestations such as microcephaly in the developing embryonic brains.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.