by A recent study published in the journal iScience sheds light on the ocular effects of Zika virus (ZIKV) infection during pregnancy and identifies potential therapeutic targets. Researchers from the Department of Ophthalmology, Visual and Anatomical Sciences at Wayne State University School of Medicine delve into the impact of ZIKV on the eyes and propose new avenues for intervention in their paper titled “Targeting ABCG1 and SREBP-2 mediated cholesterol homeostasis ameliorates Zika virus-induced ocular pathology.”
ZIKV has become a global public health concern, particularly posing risks to reproductive health. While previous research has linked congenital ZIKV infection to neurological disorders like microcephaly, there is emerging evidence of ZIKV’s association with eye abnormalities in infants. These ocular deformities include retinal lesions, microphthalmia, hemorrhagic retinopathy, retinal pigmented epithelium mottling, optic neuritis, and optic nerve hypoplasia.
Despite the severe impact of ZIKV on neurological and ocular health, there are currently no specific vaccines or antiviral treatments available. The study conducted by the team at Wayne State University investigates the role of cholesterol metabolism in ZIKV-induced eye abnormalities through a transcriptomic analysis of ZIKV-infected retinal pigment epithelial (RPE) cells, revealing significant variations in the cholesterol pathway.
Dr. Ashok Kumar, the senior author of the study, emphasized the importance of understanding the molecular mechanisms behind ZIKV-related eye abnormalities, focusing on cellular metabolism. By exploring the involvement of key regulators of cholesterol metabolism, ATP-binding cassette transporter G1 (ABCG1) and sterol response element binding protein 2 (SREBP-2), the researchers identified potential targets for therapeutic intervention.
Experiments on cell cultures demonstrated that increasing ABCG1 activity through liver X receptors (LXRs) reduced ZIKV replication, while inhibiting SREBP-2 lowered cholesterol levels and subsequently decreased viral replication. In vivo studies using mouse models with ZIKV-induced chorioretinal lesions showed promising outcomes when treated with an LXR agonist or SREBP-2 inhibitor, leading to improved ocular abnormalities and reduced inflammation.
Dr. Sneha Singh, a postdoctoral fellow in Dr. Kumar’s lab, highlighted the significance of targeting cholesterol pathway components like ABCG1 and SREBP-2 as potential therapeutic strategies for mitigating ZIKV-induced ocular complications. The implications of this study extend beyond ZIKV to other enveloped viruses, such as West Nile virus, Japanese encephalitis virus, and Dengue virus, indicating broader applicability of the findings.
Continuing their research, Dr. Kumar’s team is employing a lipidomics approach to identify lipid molecules with both proviral and antiviral properties, aiming to discover novel antiviral therapeutics. Dr. Ezemenari M. Obasi, the vice president for research at Wayne State, commended the team’s innovative efforts, emphasizing the impact of their discoveries on addressing eye abnormalities caused by ZIKV not only in Detroit but globally.
This study underscores the intricate relationship between cholesterol metabolism and ZIKV infection in the eyes, offering insights into potential therapeutic targets for addressing ZIKV-related ocular complications and potentially aiding in the development of treatments for various enveloped viruses.
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it.
