Correlation between apoptosis and in situ immune response in fatal cases of microcephaly caused by Zika Virus

• Autor(a) principal: Sousa, Jorge Rodrigues de
• Data de Publicação: 2018
• Outros Autores: Azevedo, Raimunda do Socorro da Silva, Martins Filho, Arnaldo Jorge, Araújo, Marialva Tereza Ferreira de, Cruz, Ermelinda do Rosário Moutinho da, Vasconcelos, Barbara Cristina Baldez, Cruz, Ana Cecília Ribeiro, Oliveira, Consuelo Silva de, Martins, Lívia Caricio, Vasconcelos, Beatriz Helena Baldez, Casseb, Lívia Medeiros Neves, Chiang, Jannifer Oliveira, Quaresma, Juarez Antônio Simões, Vasconcelos, Pedro Fernando da Costa
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Digital do Instituto Evandro Chagas (Patuá)
• DOI: 10.1016/j.ajpath.2018.07.009
• Texto Completo: http://patua.iec.gov.br//handle/iec/3519
• topic: Zika virus / patogenicidade; Infecção pelo Zika virus / patologia; Microcefalia / mortalidade; Infecções por Flavivirus; Apoptose / genética; Córtex Cerebral / lesões

Zika virus (ZIKV) is a single-stranded positive-sense RNA flavivirus that possesses a genome approximately 10.7 Kb in length. Although pro-inflammatory and anti-inflammatory cytokines and apoptotic markers belonging to the extrinsic and intrinsic pathways are suggested to be involved in fatal cases of ZIKV-induced microcephaly, their exact roles and associations are unclear. To address this, brain tissue samples were collected from 10 individuals, five of whom were diagnosed as ZIKV positive with microcephaly and a further five were flavivirus-negative controls that died because of other causes. Examination of material from the fatal cases of microcephaly revealed lesions in the cerebral cortex, edema, vascular proliferation, neuronal necrosis, gliosis, neuronophagy, calcifications, apoptosis, and neuron loss. The expression of various apoptosis markers in the neural parenchyma, including FasL, FAS, BAX, BCL2, and caspase 3 differed between ZIKV-positive cases and controls. Further investigation of type 1 and 2 helper T-cell cytokines confirmed a greater anti-inflammatory response in fatal ZIKV-associated microcephaly cases. Finally, an analysis of the linear correlation between tumor necrosis factor-α, IL-1β, IL-4, IL-10, transforming growth factor-β, and IL-33 expression and various apoptotic markers suggested that the immune response may be associated with the apoptotic phenomenon observed in ZIKV-induced microcephaly.