Dengue virus infects the mouse eye following systemic or intracranial infection and induces inflammatory responses

Zika virus infection of retinal cells and the developing mouse eye induces host responses that contrasts to the brain and dengue virus infection

“…It has been previously shown that DENV can infect RPE and exert functional changes (Carr et al 2017 ). Additionally, DENV RNA and inflammatory responses can be detected in the mouse eye following either a systemic or intracranial infection (Norbury et al 2020 ). Other studies have demonstrated that ZIKV can infect retinal cell types such as the retinal pigment epithelium (RPE), both primary RPE, the cell line ARPE-19, Muller cells and retinal endothelial cells in vitro (Singh et al 2017 ; Zhao et al 2017 ), and in a human fetal RPE cell line (Garcia et al 2020 ) or iPSC-derived RPE (Simonin et al 2019 ).…”

“…In contrast, DENV has been well described to cause a retinopathy, including retinal vascular disease in the posterior eye (Li et al 2017 ; Lim et al 2004 ; Teoh et al 2006 ). Our laboratory has demonstrated that DENV can infect cell types from the retina (Carr et al 2017 ), and DENV can infect the eye in animal models of adult disease (Norbury et al 2020 ). ZIKV has been demonstrated in the eye in models of in utero or post-natal mouse development (Li et al 2021 ; Zhao et al 2017 ), infection in adult mice when the IFN-response is lacking (Garcia et al 2020 ; Miner et al 2016 ; Singh et al 2019 ), and CZS can be studied in a number of animal models in the laboratory (Caine et al 2018 ; Narasimhan et al 2020 ).…”

“…In relation to infection of the brain, DENV can cause central nervous system disease, such as encephalitis in the adult, although rarely, (Li et al 2017 ) but ZIKV is a well-recognised cause of microcephaly following infection in utero (de Paula Freitas et al 2017 ; Musso and Gubler 2016 ; Musso et al 2019 ). In the laboratory, DENV can infect the brain of adult mice and replicate in microglia, neurons, oligodendrocytes, and endothelial cells (Amorim et al 2019 ; Velandia-Romero et al 2012 ) and can move from the brain to the eye (Norbury et al 2020 ), while ZIKV can infect the developing mouse brain (Noguchi et al 2020 ) and isolated or organoid cultured neuronal progenitor cells (NPC) (Qian et al 2017 ).…”

Viperin is anti-viral in vitro but is dispensable for restricting dengue virus replication or induction of innate and inflammatory responses in vivo

“…The ability of IFN to eliminate viral infection is mediated by the transcription of hundreds of ISGs such as viperin [31–33] as part of the early immune response against a range of viral infections [2, 3]. Data from our laboratory suggest a role of viperin in restricting DENV infection in vitro using primary human cells [11, 34], and that viperin is induced in MEFs [12, 25, 35] and in the brain and eye of mice in response to DENV infection [13]. Here, the role of viperin against DENV infection was investigated in a mouse model with a CRISPR/Cas-induced deletion in the Rsad gene encoding viperin [8], using MEFs in vitro and subcutaneous and intracranial DENV in vivo challenge systems in an immunocompetent background.…”

“…While viperin is induced in the mouse brain following DENV-2 intracranial (i.c.) infection [ 12 ] and in the mouse eye following systemic infection in interferon (IFN)-deficient mice [ 13 ], the antiviral role of viperin against DENV infection in vivo in immunocompetent animals is undefined. For other viral infections, in vivo viral challenge in the absence of viperin has resulted in varied outcomes; namely, enhanced CHIKV infection and CHIKV-induced footpad swelling [ 5 ], enhanced WNV mortality and infection in the brain [ 14 ], lack of an effect on IAV infection in the lung [ 15 ] and partial antiviral effect in transiently reducing viral load and spread during Langat virus (LGTV) infection in the brain [ 16 ].…”