Avaliação das alterações promovidas pela infecção pelo vírus da zika em culturas primárias de células da glia

• Ano de defesa: 2020
• Autor(a) principal: Priscila Grazieli Lopes
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; Brasil; ICB - DEPARTAMENTO DE BIOQUÍMICA E IMUNOLOGIA; Programa de Pós-Graduação em Neurociências; UFMG
• Palavras-chave em Português: ZIKV; glia; TNF-α; IL-1β; morte neuronal; Neurociências; Infecção por Zika virus; Neuroglia; Fator de Necrose Tumoral alfa; Interleucina-1beta
• Link de acesso: http://hdl.handle.net/1843/32819

Neuronal infection by Zika virus (ZIKV) has been the subject of extensive research in the past few years and many studies were focused on understanding its association with neurological syndromes such as microcephaly and Guillain Barré. Recent work from our research group (Olmo et al., 2017) has shown that ZIKV infection induced a form of non-autonomous neuronal cell death, in vitro, which can be regulated by increase of pro-inflammatory cytokines release and glutamate signaling. It is important to highlight that those results were generated in nearly pure neuronal cultures, in which very few or no astrocytes and microglia can be found. Due to the major role of glial cells in neurotransmitter metabolism and regulation of inflammatory processes in the brain, the present work was therefore aimed at the investigation of the effect of ZIKV infection in primary glial cell cultures as well as the contribution of infected glia cells in cytokine-promoted neuronal cell death. Different aspects of cellular responses were evaluated in primary cultures of glial cells infected with ZIKV for 24 and 48 hours, such as viral burden, microglia proliferation and gene-specific expression alterations. Our analyses were able to detect viral burden in 24- and 48-hours infected primary cultures demonstrating that ZIKV can successfully infect glial cells providing an in vitro model for ZIKV-induced neuro-toxicity studies. Increased expression of tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β) was observed in ZIKV-infected glial culture although no microglia proliferation seemed to be associated with it. Complementary analyses of neuronal survival and viability were also performed to verify the effect of a treatment with conditioned medium from ZIKV-infected glial cultures on primary neuronal cultures. Our results indicated that neurons treated for 24 hours with virus-inactivated conditioned medium from infected glial cells did not present significant increase in cell death when compared to uninfected controls. Strategies stablished in the present work provide an interesting model for the in vitro analyses of ZIKV-induced processes in the CNS and further studies will be carried out in order to investigate whether cellular factors released by ZIKV-infected glial cells can promote neuronal death in different conditions.