Dengue virus 3 genotype I (GI) lineage 1 (L1) isolates elicit differential cytopathic effect with syncytium formation in human glioblastoma cells (U251)

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dc.creatorAdriana de Souza Andrade
dc.creatorSofia Oliveira Campos
dc.creatorJamile Dias
dc.creatorMarco Antônio Campos
dc.creatorErna Geessien Kroon
dc.date.accessioned2025-02-14T22:17:24Z
dc.date.accessioned2025-09-08T22:54:35Z
dc.date.available2025-02-14T22:17:24Z
dc.date.issued2023-09-03
dc.format.mimetypepdf
dc.identifier.doihttps://doi.org/10.1186/s12985-023-02168-y
dc.identifier.issn1743-422X
dc.identifier.urihttps://hdl.handle.net/1843/80109
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofVirology Journal
dc.rightsAcesso Aberto
dc.subjectVirologia
dc.subjectVírus da Dengue
dc.subjectArbovírus
dc.subject.otherDengue virus
dc.subject.otherSyncytium
dc.subject.otherFlaviviridae
dc.subject.otherHuman glioblastoma cells
dc.subject.otherCytopathic effect
dc.titleDengue virus 3 genotype I (GI) lineage 1 (L1) isolates elicit differential cytopathic effect with syncytium formation in human glioblastoma cells (U251)
dc.typeArtigo de periódico
local.citation.epage13
local.citation.spage1
local.citation.volume20
local.description.resumoBackground: Dengue virus (DENV) is a Flaviviridae member classified into four antigenically distinct serotypes (DENV 1, 2, 3, and 4) and further subdivided genotypes. DENV3 is subdivided into four or five genotypes, depending on the classification adopted. Despite their high genetic proximity, as revealed by phylogenetic complete polyprotein analysis, DENV3 MG-20 and DENV3 PV_BR showed different neurovirulence in mice models. Our group identified six amino acid mutations in protein E, including the E62K and E123Q, which may affect interactions of hydrophobic clusters on domain II, thus leading to the observed differences in the studied viruses. Methods Human glioblastoma cells (U251) derived from a malignant glioblastoma tumor by explant technique were infected by the DENV3 GIL1 isolates DENV3 MG-20 and DENV3 PV_BR and analyzed by plaque assays and titration, optical, immunofluorescence, and transmission electronic microscopy. Results: The two isolates showed different cytopathic effects (CPE) and fusogenic patterns, further confirmed by indirect immunofluorescence. Transmission electron microscopy revealed intense cytopathic effects in DENV3 MG-20 infected U251 cells, displaying endoplasmic reticulum hypertrophy and turgid vesicles with proteins and multiple viruses, distinct from DENV3 PV_BR infected cells. It is hypothesized that the different amino acids in the DENV3 MG-20 isolate are related to an increased membrane fusion ability in viral infection, thus facilitating immune system evasion and increased chances of central nervous system cell infection. Conclusion: These results emphasize the biological differences between the isolates, which could be a critical factor in host-virus interaction and severe dengue development. Our study presents comparative results of highly similar isolates with the potential to generate more subsidies for a deeper understanding of the DENV pathogenesis. The neurotropism of the isolate DENV3 MG-20 (belonging to the DENV3 GI L1 genotype) showing infection of nervous system cells (U251) could contribute to understanding neurological dengue disease.
local.identifier.orcidhttps://orcid.org/0000-0003-2394-8219
local.identifier.orcidhttps://orcid.org/0000-0001-9915-260X
local.identifier.orcidhttps://orcid.org/0000-0003-2721-3826
local.publisher.countryBrasil
local.publisher.departmentICB - DEPARTAMENTO DE MICROBIOLOGIA
local.publisher.initialsUFMG
local.url.externahttps://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02168-y#rightslink

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