茲卡病毒對微膠細胞之影響

Abstract

Zika virus (ZIKV) is a flavivirus and mostly causes mild symptoms in humans. The recent ZIKV outbreak in Brazil during 2015 to 2016 raised public concerns, since neurological malfunction such as Guillain-Barré syndrome and microcephaly were linked to ZIKV infection. Microglia, the resident immune cells in the central nervous system, was shown to be ZIKV’s target. In this thesis study, we aim to elucidate the roles of microglia in ZIKV infection by using human microglial cells (HMC3) and neuroblastoma cells (BE(2)-C). Results showed that HMC3 cells were more susceptible to ZIKV infection than BE(2)-C cells, and virus titer increased earlier than that from BE(2)-C cells. Also, ZIKV infection could activate microglia cells. In studies of interplay between the two cells, co-culture with HMC3 cells increased BE(2)-C cell growth, whereas the promotion of BE(2)-C cell growth was decreased when infected with ZIKV. Moreover, ZIKV can be transmitted to BE(2)-C cells through a cell-cell-contact manner when co-cultured with microglia cells, demonstrated by transwell assay and antibody neutralization assay. In addition, through mRNA screening, we suggested ZIKV infection activated the neuroinflammation signaling pathway in HMC3 cells and may lead the cells to a pro-inflammatory neurotoxic state (M1).