Document Type

Article

Publication Date

9-15-2020

Department

Biological Sciences

School

Biological, Environmental, and Earth Sciences

Abstract

Zika virus (ZIKV) has been recently recognized as a causative agent of newborn microcephaly, as well as other neurological consequences. A less well recognized comorbidity of prenatal ZIKV infection is hearing loss, but cases of hearing impairment following adult ZIKV infection have also been recognized. Diminished hearing following prenatal ZIKV infection in a mouse model has been reported, but no cellular consequences were observed. We examined the effects of ZIKV infection on inner ear cellular integrity and expression levels of various proteins important for cochlear function in type I interferon receptor null (Ifnar1−/−) mice following infection at 5–6 weeks of age. We show that ZIKV antigens are present in cells within the cochlear epithelium, lateral wall, spiral limbus and spiral ganglion. Here we show that ZIKV infection alters cochlear expression of genes that signal cell damage (S100B), transport fluids (AQP1), are gaseous transmitters (eNOs) and modulate immune response (F4/80). Morphological analyses shows that not only are cochlear structures compromised by ZIKV infection, but damage also occurs in vestibular end organs. ZIKV produces a graded distribution of cellular damage in the cochlea, with greatest damage in the apex similar to that reported for cytomegalovirus (CMV) infection. The graded distribution of damage may indicate a differential susceptibility to ZIKV along the cochlear tonotopic axis. Collectively, these data are the first to show the molecular and morphological damage to the inner ear induced by ZIKV infection in adults and suggests multiple mechanisms contributing to the hearing loss reported in the human population.

Comments

© 2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/

Publication Title

Hearing Research

Volume

395

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