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

Our mouse model is also useful for studying ZIKV's tissue tropism and potential complications of severe ZIKV infection. In addition to the reported findings of detectable virus particles and/or RNA in the brain, spinal cord, kidney, spleen, liver, testis, ovary, heart, lung, muscle, and blood of types I/II interferon-signaling-/receptor-deficient mice with ZIKV infection, our study identified intestine, pancreas, and salivary gland as other possible tissues and anatomical sites for virus infection (Dick, 1952; Lazear et al., 2016; Dowall et al., 2016; Aliota et al., 2016; Rossi et al., 2016) . This tissue tropism of ZIKV in our mouse model concurs with the in-vitro observation that ZIKV efficiently replicates in diverse cell types of neuronal, testicular, prostatic, renal, intestinal, hepatic, and placental origin (Chan et al., 2016b; Brault et al., 2016; Hughes et al., 2016) . Such degree of virus dissemination and multiorgan involvement is also compatible with the clinical findings in patients with severe and/or fatal ZIKV infection, in whom viral particles and/or RNA were detected in multiple organs at post-mortem examination (Pan American Health Organization/World Health Oganization (PAHO/WHO), 2015; Sarmiento-Ospina et al., 2016; Arzuza-Ortega et al., 2016) . While inflammatory neurological complications, such as Guillain-Barré syndrome, meningoencephalitis, and myelitis, have been recently reported in patients with ZIKV infection, inflammatory disorders of the other non-neuronal tissues were not well recognized (Cao-Lormeau et al., 2016; Carteaux et al., 2016; Mecharles et al., 2016) . Our findings showed that inflammation could be observed in multiple organs including the testis, kidney, spleen, liver, intestine, pancreas, lung, and salivary gland outside the nervous system.