Absence of Interferon-inducible protein 10 increases enterovirus 71 lethality in mice

• Main Authors: Chia-ChunTsai, 蔡佳純
• Other Authors: Shun-hua Chen
• Format: Others
• Language: en_US
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/69629714555849917838

碩士 === 國立成功大學 === 微生物及免疫學研究所 === 98 === Enterovirus 71 (EV71) has induced fatal encephalitis in hundreds of thousands of young children in the Asia-Pacific region in the past decade. The levels of several chemokines in the plasma and cerebrospinal fluid of infected patients with brain stem encephalitis are elevated. Among these chemokines, the level of interferon-gamma-inducible protein (IP)-10 is shown to positively correlate with the disease severity. The role of IP-10 in EV71 infection is still unknown. Therefore, we used a mouse infection model to address this issue. Results revealed that IP-10 protein was induced in the brain and serum of infected mice with levels positively correlated with tissue viral loads and death rates. To investigate the role of IP-10 in EV71 infection, we compared the survival rates of wild-type mice and IP-10-deficient (IP-10-/-) mice after infection. The survival rate of wild-type mice was significantly higher than that of IP-10-/- mice by 45 %. In addition, we harvested the organs of infected mice to determine viral loads. The mean viral titers in most organs of IP-10-/- mice were higher than those of wild-type mice, with significant differences found in the central nervous system. To study the interaction between IP-10 and EV71, we treated IP-10 and control medium in infected mouse neuronal cells to detect the difference of viral titers. Our result showed that IP-10 did not have direct antiviral effect in vitro. IP-10 is a potent chemoattractant for activated T cells and NK cells, so we quantified these cells in infected tissues by flow cytometry. The mean numbers of CD4+ T cells, CD8+ T cells, and B cells in the spleens and brains of wild-type mice were higher than those of IP-10-/- mice with significant differences found in the spleens. Additionally, the levels of another two chemokines, monokine induced by gamma interferon (Mig) and monocyte chemotactic protein-1 (MCP-1) which are increased in EV71-infected patients with brain stem encephalitis, were reduced in IP-10-/- mice compared to wild-type mice. Collectively, our results show that the absence of IP-10 increases the lethality of EV71-infected mice with reduced leukocyte influx and elevated viral loads in tissues.