Zika virus infection of retinal cells and the developing mouse eye induces host responses that contrasts to the brain and dengue virus infection
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Published:2023-04
Issue:2
Volume:29
Page:187-202
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ISSN:1355-0284
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Container-title:Journal of NeuroVirology
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language:en
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Short-container-title:J. Neurovirol.
Author:
Cowell E., Kris L. P., Bracho-Granado G., Jaber H., Smith J. R., Carr J. M.ORCID
Abstract
AbstractZika virus (ZIKV) infection causes ocular and neurological pathologies with ZIKV-induction of developmental abnormalities following in utero infection a major concern. The study here has compared ZIKV and the related dengue virus (DENV) infection in the eye and brain. In vitro, both ZIKV and DENV could infect cell lines representing the retinal pigmented epithelium, endothelial cells, and Mueller cells, with distinct innate responses in each cell type. In a 1-day old mouse challenge model, both ZIKV and DENV infected the brain and eye by day 6 post-infection (pi). ZIKV was present at comparable levels in both tissues, with RNA increasing with time post-infection. DENV infected the brain, but RNA was detected in the eye of less than half of the mice challenged. NanoString analysis demonstrated comparable host responses in the brain for both viruses, including induction of mRNA for myosin light chain-2 (Mly2), and numerous antiviral and inflammatory genes. Notably, mRNA for multiple complement proteins were induced, but C2 and C4a were uniquely induced by ZIKV but not DENV. Consistent with the viral infection in the eye, DENV induced few responses while ZIKV induced substantial inflammatory and antiviral responses. Compared to the brain, ZIKV in the eye did not induce mRNAs such as C3, downregulated Retnla, and upregulated CSF-1. Morphologically, the ZIKV-infected retina demonstrated reduced formation of specific retinal layers. Thus, although ZIKV and DENV can both infect the eye and brain, there are distinct differences in host cell and tissue inflammatory responses that may be relevant to ZIKV replication and disease.
Funder
National Health and Medical Research Council Channel 7 Children's Research Foundation Flinders University
Publisher
Springer Science and Business Media LLC
Subject
Virology,Cellular and Molecular Neuroscience,Neurology (clinical),Neurology
Reference57 articles.
1. Agrawal R, Gunasekeran DV, Agarwal A, Carreño E, Aggarwal K, Gupta B, Raje D, Murthy SI, Westcott M, Chee SP, McCluskey P, Ling HS, Teoh S, Cimino L, Biswas J, Narain S, Agarwal M, Mahendradas P, Khairallah M, Jones N, Tugal-Tutkun I, Babu K, Basu S, Lee R, Al-Dhibi H, Bodaghi B, Invernizzi A, Goldstein DA, Herbort CP, Barisani-Asenbauer T, González-López JJ, Androudi S, Bansal R, Moharana B, Mahajan S, Esposti S, Tasiopoulou A, Nadarajah S, Agarwal M, Abraham S, Vala R, Lord J, Singh R, Sharma A, Sharma K, Zierhut M, Kon OM, Kempen J, Cunningham ET, Rousselot A, Nguyen QD, Pavesio C, Gupta V (2018) The collaborative ocular tuberculosis study (COTS)-1: a multinational description of the spectrum of choroidal involvement in 245 patients with tubercular uveitis. Ocul Immunol Inflamm: 1–11 2. Al-Shujairi WH, Clarke JN, Davies LT, Alsharifi M, Pitson SM, Carr JM (2017) Intracranial injection of dengue virus induces interferon stimulated genes and CD8+ T Cell infiltration by sphingosine kinase 1 independent pathways. PLoS ONE 12:e0169814 3. Amorim JFS, Azevedo AS, Costa SM, Trindade GF, Basílio-de-Oliveira CA, Gonçalves AJS, Salomão NG, Rabelo K, Amaral R, Geraldo LHM, Lima FRS, Mohana-Borges R, Paes MV, Alves AMB (2019) Dengue infection in mice inoculated by the intracerebral route: neuropathological effects and identification of target cells for virus replication. Sci Rep 9:17926 4. Bharadwaj AS, Appukuttan B, Wilmarth PA, Pan Y, Stempel AJ, Chipps TJ, Benedetti EE, Zamora DO, Choi D, David LL, Smith JR (2013) Role of the retinal vascular endothelial cell in ocular disease. Prog Retin Eye Res 32:102–180 5. Bronte V, Serafini P, Mazzoni A, Segal DM, Zanovello P (2003) L-arginine metabolism in myeloid cells controls T-lymphocyte functions. Trends Immunol 24:302–306
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