ZIKA virus infection causes persistent chorioretinal lesions

Manangeeswaran, Mohanraj; Kielczewski, Jennifer L.; Sen, H. Nida; Xu, Biying C.; Ireland, Derek. D. C.; McWilliams, Ian L.; Chan, Chi-Chao; Caspi, Rachel R.; Verthelyi, Daniela

doi:10.1038/s41426-018-0096-z

Title: ZIKA virus infection causes persistent chorioretinal lesions

Abstract

Zika-infected patients can have eye involvement ranging from mild conjunctivitis to severe chorioretinal lesions, however the possible long-term sequelae of infection and timeline to recovery remain unknown. Here we describe the partial recovery of chorioretinal lesions in an immunocompetent patient diagnosed with bilateral posterior uveitis associated with Zika infection and show that some lesions resolved with focal atrophy evident as pigmentary changes on funduscopy. To better understand the progression of the lesions and correlate the changes in fundus imaging with local viral load, immune responses, and retinal damage, we developed a symptomatic mouse model of ocular Zika virus infection. Imaging of the fundus revealed multiple hypopigmentary patches indicative of chorioretinal degeneration as well as thinning of the retina that mirror the lesions in patients. Microscopically, the virus primarily infected the optic nerve, retinal ganglion cells, and inner nuclear layer cells, showing thinning of the outer plexiform layer. During acute infection, the eyes showed retinal layer disorganization, retinitis, vitritis, and focal choroiditis, with mild cellular infiltration and increased expression of tumor necrosis factor, interferon-γ, granzyme B, and perforin. Focal areas of gliosis and retinal degeneration persisted 60 dpi. The model recapitulates features of ZIKA infections in patients and should help elucidatemore »« less

Authors:

Manangeeswaran, Mohanraj ^[1]; Kielczewski, Jennifer L. ^[2]; Sen, H. Nida ^[2]; Xu, Biying C. ^[2]; Ireland, Derek. D. C. ^[1]; McWilliams, Ian L. ^[1];

^[2]; Caspi, Rachel R. ^[2]; Verthelyi, Daniela ^[1]

Food and Drug Administration (FDA), Silver Spring, MD (United States). Center for Drug Evaluation and Research. Office of Biotechnology Products. Division of Biotechnology Review and Research-III
National Institutes of Health, Bethesda MD (United States). Lab. of Immunology

Publication Date:: Fri May 25 00:00:00 EDT 2018

Research Org.:: Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)

Sponsoring Org.:: USDOE Office of Science (SC)

OSTI Identifier:: 1624035

Grant/Contract Number:: SC0014664

Resource Type:: Accepted Manuscript

Journal Name:: Emerging Microbes & Infections

Additional Journal Information:: Journal Volume: 7; Journal Issue: 1; Journal ID: ISSN 2222-1751

Publisher:: Nature Publishing Group

Country of Publication:: United States

Language:: English

Subject:: 59 BASIC BIOLOGICAL SCIENCES; Immunology; Microbiology

Citation Formats


                    Manangeeswaran, Mohanraj, Kielczewski, Jennifer L., Sen, H. Nida, Xu, Biying C., Ireland, Derek. D. C., McWilliams, Ian L., Chan, Chi-Chao, Caspi, Rachel R., and Verthelyi, Daniela. ZIKA virus infection causes persistent chorioretinal lesions.  United States: N. p., 2018. 
Web.  doi:10.1038/s41426-018-0096-z.

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                    Manangeeswaran, Mohanraj, Kielczewski, Jennifer L., Sen, H. Nida, Xu, Biying C., Ireland, Derek. D. C., McWilliams, Ian L., Chan, Chi-Chao, Caspi, Rachel R., & Verthelyi, Daniela. ZIKA virus infection causes persistent chorioretinal lesions.  United States.  https://doi.org/10.1038/s41426-018-0096-z

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                    Manangeeswaran, Mohanraj, Kielczewski, Jennifer L., Sen, H. Nida, Xu, Biying C., Ireland, Derek. D. C., McWilliams, Ian L., Chan, Chi-Chao, Caspi, Rachel R., and Verthelyi, Daniela. Fri .  
"ZIKA virus infection causes persistent chorioretinal lesions".  United States.  https://doi.org/10.1038/s41426-018-0096-z.  https://www.osti.gov/servlets/purl/1624035.

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@article{osti_1624035,

  title        = {ZIKA virus infection causes persistent chorioretinal lesions},

  author       = {Manangeeswaran, Mohanraj and Kielczewski, Jennifer L. and Sen, H. Nida and Xu, Biying C. and Ireland, Derek. D. C. and McWilliams, Ian L. and Chan, Chi-Chao and Caspi, Rachel R. and Verthelyi, Daniela},

  abstractNote = {Zika-infected patients can have eye involvement ranging from mild conjunctivitis to severe chorioretinal lesions, however the possible long-term sequelae of infection and timeline to recovery remain unknown. Here we describe the partial recovery of chorioretinal lesions in an immunocompetent patient diagnosed with bilateral posterior uveitis associated with Zika infection and show that some lesions resolved with focal atrophy evident as pigmentary changes on funduscopy. To better understand the progression of the lesions and correlate the changes in fundus imaging with local viral load, immune responses, and retinal damage, we developed a symptomatic mouse model of ocular Zika virus infection. Imaging of the fundus revealed multiple hypopigmentary patches indicative of chorioretinal degeneration as well as thinning of the retina that mirror the lesions in patients. Microscopically, the virus primarily infected the optic nerve, retinal ganglion cells, and inner nuclear layer cells, showing thinning of the outer plexiform layer. During acute infection, the eyes showed retinal layer disorganization, retinitis, vitritis, and focal choroiditis, with mild cellular infiltration and increased expression of tumor necrosis factor, interferon-γ, granzyme B, and perforin. Focal areas of gliosis and retinal degeneration persisted 60 dpi. The model recapitulates features of ZIKA infections in patients and should help elucidate the mechanisms underlying the damage to the eyes and aid in the development of effective therapeutics.},

  doi          = {10.1038/s41426-018-0096-z},

  journal      = {Emerging Microbes & Infections},

  number       = 1,

  volume       = 7,

  place        = {United States},

  year         = {Fri May 25 00:00:00 EDT 2018},

  month        = {Fri May 25 00:00:00 EDT 2018}

}

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Figures / Tables:

Fig. 1: Posterior lesions in ZIKV-infected patient. a, b, c Fundus photos illustrate the evolution of outer retinal lesions with increasing pigmentation over time. d, e, f Fundus autofluorescence (FAF) images corresponding to outer retinal lesions show hyperautofluorescence at the initial presentation that becomes hypoautofluorescent by 5 months, indicating partialmore »

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