June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
ZIKA VIRUS-INDUCED AUTOPHAGY PROMOTES VIRAL REPLICATION IN THE OCULAR TISSUE AND INHIBITION OF AUTOPHAGY RESTRICTS ITS TRANSMISSION
Author Affiliations & Notes
  • Faraz Ahmad
    Department of Ophthalmology, Mason Eye Institute, University of Missouri School of Medicine, Columbia, Missouri, United States
  • Pawan Kumar Singh
    Department of Ophthalmology, Mason Eye Institute, University of Missouri School of Medicine, Columbia, Missouri, United States
  • Footnotes
    Commercial Relationships   Faraz Ahmad None; Pawan Kumar Singh None
  • Footnotes
    Support  NEI/NIH R01:EY032495
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 150. doi:
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      Faraz Ahmad, Pawan Kumar Singh; ZIKA VIRUS-INDUCED AUTOPHAGY PROMOTES VIRAL REPLICATION IN THE OCULAR TISSUE AND INHIBITION OF AUTOPHAGY RESTRICTS ITS TRANSMISSION. Invest. Ophthalmol. Vis. Sci. 2023;64(8):150.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Zika virus (ZIKV) is a reemerging threat that recently affected >1.6 million people in >33 countries including the USA. ZIKV caused microcephaly and ocular abnormalities including congenital glaucoma in infants born to ZIKV-infected moms. However, the pathobiology of ZIKV-induced ocular complications in general and congenital glaucoma in particular, remain unclear. In this study, we investigated the role of autophagy in ZIKV transmission and ocular complications.

Methods : The primary human TM cells (HTMC) and GTM3 cell line were challenged with ZIKV-PRVAB59 strain in the presence and absence of autophagy inhibitors [Bafilomycin, hydroxychloroquine (HCQ)]. Autophagy markers (LC3-II and SQSTM1/p62) were evaluated using western blotting and immunofluorescence staining. For in vivo studies, B6 WT and IFNAR1-/- mice were challenged with ZIKV with or without HCQ treatment. Intraocular pressure (IOP) was recorded, and fundus imaging were performed to evaluate disease pathology.

Results : ZIKV permissively infected HTMC and GTM3 cells and induced autophagy. ZIKV also induced autophagy in mouse ocular tissue and elevated IOP. Autophagy inhibition dramatically reduced ZIKV replication and associated inflammatory response in HTMC. An FDA-approved drug, HCQ administration ameliorated ZIKV-induced ocular pathology in mice.

Conclusions : Our study for the first time demonstrated that ZIKV induces autophagy in ocular tissue for their survival, and autophagy inhibition restricts viral burden. These results suggest that modulation of autophagy could be a potential therapeutic avenue for controlling ZIKV-induced ocular complications.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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