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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.
- Source :
-
EBioMedicine [EBioMedicine] 2016 Dec; Vol. 14, pp. 112-122. Date of Electronic Publication: 2016 Nov 12. - Publication Year :
- 2016
-
Abstract
- Background: Disseminated 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.<br />Methods: We developed a novel mouse model for ZIKV infection by immunosuppressing BALB/c mice with dexamethasone.<br />Results: Dexamethasone-immunosuppressed male mice (6-8weeks) 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 (10dpi), which warranted euthanasia at 12dpi. Viral loads in blood and most tissues at 5dpi were significantly higher than those at 12dpi (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).<br />Conclusions: Besides 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.<br /> (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Brain immunology
Brain metabolism
Brain pathology
Dexamethasone adverse effects
Disease Models, Animal
Female
Kidney immunology
Kidney metabolism
Kidney pathology
Male
Mice
Orchitis drug therapy
Viral Load
Zika Virus Infection drug therapy
Zika Virus Infection pathology
Antiviral Agents pharmacology
Immunocompromised Host
Interferon Type I pharmacology
Orchitis virology
Zika Virus drug effects
Zika Virus immunology
Zika Virus Infection immunology
Zika Virus Infection virology
Subjects
Details
- Language :
- English
- ISSN :
- 2352-3964
- Volume :
- 14
- Database :
- MEDLINE
- Journal :
- EBioMedicine
- Publication Type :
- Academic Journal
- Accession number :
- 27884655
- Full Text :
- https://doi.org/10.1016/j.ebiom.2016.11.017