Zika Virus Infection in Dexamethasone-immunosuppressed Mice Demonstrating Disseminated Infection with Multi-organ Involvement Including Orchitis Effectively Treated by Recombinant Type I Interferons

Chan, Jasper Fuk-Woo; Zhang, Anna Jinxia; Chan, Chris Chung-Sing; Yip, Cyril Chik-Yan; Mak, Winger Wing-Nga; Zhu, Houshun; Poon, Vincent Kwok-Man; Tee, Kah-Meng; Zhu, Zheng; Cai, Jian-Piao; Tsang, Jessica Oi-Ling; Chik, Kenn Ka-Heng; Yin, Feifei; Chan, Kwok-Hung; Kok, Kin-Hang; Jin, Dong-Yan; Au-Yeung, Rex Kwok-Him; Yuen, Kwok-Yung

were consistently more significant than those of their comparators, including the ZIKV-inoculated mice without dexamethasone immunosuppression (groups 3 and 4) and mock-infected mice without dexamethasone immunosuppression (groups 7 and 8) starting at 1 dpi (P b 0.05). Minimal histological changes and inflammatory infiltrates were seen in the tissues of the male and female mice with dexamethasone immunosuppression and ZIKV inoculation (groups 1 and 2). On the other hand, ZIKV-NS1 protein expression was detected by immunohistochemical staining in most tissues of these mice, but not in dexamethasone-immunosuppressed mice with mock infection (groups 5 and 6), suggesting that the viral protein expression was specific and not related to dexamethasone effects (Fig. 2) . The dexamethasone-immunosuppressed mice with ZIKV inoculation (groups 1 and 2) also had high mean viral loads in blood and most tissues at 5 dpi, especially in the testis/epididymis, ovary/uterus, prostate, spleen, and pancreas (Figs. 3A and B and S1A and B). These findings at 5 dpi were suggestive of disseminated but non-lethal ZIKV infection involving different organs with minimal inflammatory response due to dexamethasone immunosuppression.