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

2016; Elsevier BV; Volume: 14; Linguagem: Inglês

10.1016/j.ebiom.2016.11.017

2352-3964

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

Virology and Viral Diseases

BackgroundDisseminated or fatal Zika virus (ZIKV) infections were reported in immunosuppressed patients. Existing interferon-signaling/receptor-deficient mouse models may not be suitable for evaluating treatment effects of recombinant interferons.MethodsWe developed a novel mouse model for ZIKV infection by immunosuppressing BALB/c mice with dexamethasone.ResultsDexamethasone-immunosuppressed male mice (6–8 weeks) developed disseminated infection as evidenced by the detection of ZIKV-NS1 protein expression and high viral loads in multiple organs. They had ≥10% weight loss and high clinical scores soon after dexamethasone withdrawal (10 dpi), which warranted euthanasia at 12 dpi. Viral loads in blood and most tissues at 5 dpi were significantly higher than those at 12 dpi (P < 0.05). Histological examination revealed prominent inflammatory infiltrates in multiple organs, and CD45+ and CD8+ inflammatory cells were seen in the testis. These findings suggested that clinical deterioration occurred during viral clearance by host immune response. Type I interferon treatments improved clinical outcome of mice (100% vs 0% survival).ConclusionsBesides virus dissemination, inflammation of various tissues, especially orchitis, may be potential complications of ZIKV infection with significant implications on disease transmission and male fertility. Interferon treatment should be considered in patients at high risks for ZIKV-associated complications when the potential benefits outweigh the side effects of treatment.