Zika virus leads to olfactory disorders in mice by targeting olfactory ensheathing cells.

Autor:	Zhou J; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China., Guan MY; Department of Respiratory Medicine, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 10010, China., Li RT; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China., Qi YN; State Key Laboratory of Proteomics, National Center for Protein Science (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China., Yang G; State Key Laboratory of Proteomics, National Center for Protein Science (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China., Deng YQ; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China., Li XF; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China., Li L; Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China., Yang X; State Key Laboratory of Proteomics, National Center for Protein Science (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China., Liu JF; Department of Otorhinolaryngology, China-Japan Friendship Hospital, Beijing 100029, China., Qin CF; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China; Research Unit of Discovery and Tracing of Natural Focus Diseases, Chinese Academy of Medical Sciences, Beijing, China. Electronic address: qincf@bmi.ac.cn.
Jazyk:	angličtina
Zdroj:	EBioMedicine [EBioMedicine] 2023 Mar; Vol. 89, pp. 104457. Date of Electronic Publication: 2023 Feb 03.
DOI:	10.1016/j.ebiom.2023.104457
Abstrakt:	Background: Zika virus (ZIKV) is an emerging arbovirus of the genus flavivirus that is associated with congenital Zika syndrome (CZS) in newborns. A wide range of clinical symptoms including intellectual disability, speech delay, coordination or movement problems, and hearing and vision loss, have been well documented in children with CZS. However, whether ZIKV can invade the olfactory system and lead to post-viral olfactory dysfunction (PVOD) remains unknown. Methods: We investigated the susceptibility and biological responses of the olfactory system to ZIKV infection using mouse models and human olfactory organoids derived from patient olfactory mucosa. Findings: We demonstrate that neonatal mice infected with ZIKV suffer from transient olfactory dysfunction when they reach to puberty. Moreover, ZIKV mainly targets olfactory ensheathing cells (OECs) and exhibits broad cellular tropism colocalizing with small populations of mature/immature olfactory sensory neurons (mOSNs/iOSNs), sustentacular cells and horizontal basal cells in the olfactory mucosa (OM) of immunodeficient AG6 mice. ZIKV infection induces strong antiviral immune responses in both the olfactory mucosa and olfactory bulb tissues, resulting in the upregulation of proinflammatory cytokines/chemokines and genes related to the antiviral response. Histopathology and transcriptomic analysis showed typical tissue damage in the olfactory system. Finally, by using an air-liquid culture system, we showed that ZIKV mainly targets sustentacular cells and OECs and support robust ZIKV replication. Interpretation: Our results demonstrate that olfactory system represents as significant target for ZIKV infection, and that PVOD may be neglected in CZS patients. Funding: Stated in the acknowledgment. Competing Interests: Declaration of interests The authors declare that they have no conflict of interests. (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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