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. 2019 Dec 20;9:433. doi: 10.3389/fcimb.2019.00433

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Copyright © 2019 Tian, Shi, Xiao, Liu, She, Wu, An, Hao and Soomro.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Increased pro-inflammatory responses were examined in HEV infected animal brain tissues. HEV-RNA positive brain tissues collected on 14, 21, and 28 dpi were used for immunohistochemistry study of TNFα (rabbit polyclonal IgG), IL-1β (rabbit polyclonal IgG), and IBA1 (rabbit polyclonal IgG). Goat anti-rabbit IgG was chosen as secondary antibody. The positive signal was measured via the Motic Med 6.0 CMIAS Image Analysis System. (A,B) Positive signal of TNFα was diffusely observed in a large number of microglial cells, astrocytes and few pyramidal neurons in HEV infected animal brain tissues, and expression level was significantly induced compared with mock group (**p < 0.01). (C,D) The expression level of activated IL-1β was found in microglia, astrocytes, and few neuronal cytoplasms and was significantly increased in HEV infected brain sections compared with tissues from mock group (**p < 0.01). (E,F) Positive expression of IBA1 was detected in microglial cells with significantly elevated levels in brain tissues infected with HEV compared with mock group (**p < 0.01).