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      Lassa Virus Targeting of Anterior Uvea and Endothelium of Cornea and Conjunctiva in Eye of Guinea Pig Model

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          Abstract

          Lassa virus (LASV), a hemorrhagic fever virus endemic to West Africa, causes conjunctivitis in patients with acute disease. To examine ocular manifestations of LASV, we histologically examined eyes from infected guinea pigs. In fatal disease, LASV immunostaining was most prominent in the anterior uvea, especially in the filtration angle, ciliary body, and iris and in and around vessels in the bulbar conjunctiva and peripheral cornea, where it co-localized with an endothelial marker (platelet endothelial cell adhesion molecule). Antigen was primarily associated with infiltration of T-lymphocytes around vessels in the anterior uvea and with new vessel formation at the peripheral cornea. In animals that exhibited clinical signs but survived infection, eyes had little to no inflammation and no LASV immunostaining 6 weeks after infection. Overall, in this model, LASV antigen was restricted to the anterior uvea and was associated with mild chronic inflammation in animals with severe disease but was not detected in survivors.

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          Anterior eye development and ocular mesenchyme: new insights from mouse models and human diseases.

          During development of the anterior eye segment, cells that originate from the surface epithelium or the neuroepithelium need to interact with mesenchymal cells, which predominantly originate from the neural crest. Failures of proper interaction result in a complex of developmental disorders such Peters' anomaly, Axenfeld-Rieger's syndrome or aniridia. Here we review the role of transcription factors that have been identified to be involved in the coordination of anterior eye development. Among these factors is PAX6, which is active in both epithelial and mesenchymal cells during ocular development, albeit at different doses and times. We propose that PAX6 is a key element that synchronizes the complex interaction of cell types of different origin, which are all needed for proper morphogenesis of the anterior eye. We discuss several molecular mechanisms that might explain the effects of haploinsufficiency of PAX6 and other transcription factors, and the broad variation of the resulting phenotypes. Copyright 2004 Wiley Periodicals, Inc.
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            Lassa virus infection of rhesus monkeys: pathogenesis and treatment with ribavirin.

            Rhesus monkeys were experimentally infected with Lassa virus to establish their suitability as a nonhuman primate model for the human disease and to test the protective efficacy of ribavirin, an antiviral drug. Six of 10 untreated control monkeys died after subcutaneous inoculation of 10(6.1) plaque-forming units of Lassa virus (strain Josiah). Infectivity titrations of tissue homogenates from the six dead monkeys indicated significant replication in all tissues tested except the central nervous system. This distribution of virus was confirmed by direct immunofluorescence examination of cryostat-sectioned tissues. Ribavirin was beneficial in the treatment of two groups of infected monkeys. Four monkeys first treated on the day of viral inoculation experienced only mild clinical disease; four monkeys first treated five days later experienced a more severe illness. None of the eight monkeys treated with ribavirin died. Viremia titers and elevations of levels of serum transaminases in treated monkeys were significantly lower than in controls. Ribavirin may be beneficial in the treatment of humans exposed to this life-threatening virus.
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              Identification and pathological characterization of persistent asymptomatic Ebola virus infection in rhesus monkeys

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                Author and article information

                Journal
                Emerg Infect Dis
                Emerging Infect. Dis
                EID
                Emerging Infectious Diseases
                Centers for Disease Control and Prevention
                1080-6040
                1080-6059
                May 2019
                : 25
                : 5
                : 865-874
                Affiliations
                [1]Centers for Disease Control and Prevention, Atlanta, Georgia, USA
                Author notes
                Address for correspondence: Jessica R. Spengler, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Mailstop H18-SB, Atlanta, GA 30329-4027, USA; email: JSpengler@ 123456cdc.gov
                Article
                18-1254
                10.3201/eid2505.181254
                6478213
                31002065
                c348a620-0bfe-442d-a606-6b745d78d98c
                History
                Categories
                Research
                Research
                Lassa Virus Targeting of Anterior Uvea and Endothelium of Cornea and Conjunctiva in Eye of Guinea Pig Model

                Infectious disease & Microbiology
                lassa fever,lassa virus,viral hemorrhagic fever,ocular,eye,anterior uvea,endothelial cells,guinea pig,viruses,zoonoses

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