Study reveals crucial insights into the ocular effects of Zika virus infection during pregnancy

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A groundbreaking study published successful nan diary iScience presents important insights into nan ocular effects of Zika microorganism infection during gestation and offers promising avenues for therapeutic intervention.

Produced by a squad of researchers successful nan Department of Ophthalmology, Visual and Anatomical Sciences astatine nan Wayne State University School of Medicine, nan paper, "Targeting ABCG1 and SREBP-2 mediated cholesterin homeostasis ameliorates Zika virus-induced ocular pathology," provides compelling grounds of nan engagement of cholesterin metabolism successful ZIKV-related oculus abnormalities.

Zika virus, aliases ZIKV, has emerged arsenic a nationalist wellness threat and poses important challenges to reproductive wellness worldwide. While congenital ZIKV infection has been shown to origin neurological disorders, chiefly microcephaly – abnormal shrinking of nan caput circumference – respective objective studies person linked ZIKV to ocular deformities successful infants. These see retinal lesions, microphthalmia, hemorrhagic retinopathy, retinal pigmented epithelium mottling, optic neuritis and hypoplasia of nan optic nerve.

Despite nan ZIKV infection causing terrible neurological and ocular abnormalities successful infants, nary circumstantial vaccines aliases antiviral treatments are available. In their research, nan squad conducted a transcriptomic study of ZIKV-infected retinal pigment epithelial (RPE) cells, revealing important alterations successful nan cholesterin pathway.

Our study aimed to uncover nan molecular mechanisms underlying ZIKV-related oculus abnormalities, pinch a attraction connected cellular metabolism. By elucidating nan roles of cardinal players successful cholesterin metabolism, we sought to place imaginable targets for therapeutic intervention."

Ashok Kumar, Ph.D., professor of ophthalmology, ocular and anatomical sciences, and elder writer of nan study

The researchers investigated nan functional roles of ATP-binding cassette transporter G1 (ABCG1) and sterol consequence constituent binding macromolecule 2 (SREBP-2), 2 captious regulators of cholesterin metabolism, during ocular ZIKV infection. Their compartment civilization experiments demonstrated that accrued ABCG1 activity, mediated via liver X receptors (LXRs), led to reduced ZIKV replication, while inhibition of SREBP-2 reduced viral replication by lowering cholesterin levels.

In vivo studies utilizing rodent models of ZIKV-induced chorioretinal lesions revealed that curen pinch an LXR agonist aliases SREBP-2 inhibitor mitigated ocular abnormalities associated pinch ZIKV infection. These treatments were accompanied by decreased look of inflammatory mediators and accrued activation of antiviral consequence genes.

"This study highlights nan intricate interplay betwixt cholesterin metabolism and ZIKV infection successful nan eye," explained Sneha Singh, Ph.D., a postdoctoral chap successful Kumar's lab. "Our findings propose that targeting cholesterin pathway components, specified arsenic ABCG1 and SREBP-2, could connection promising therapeutic strategies for mitigating ZIKV-induced ocular complications."

"The implications of our study widen beyond Zika virus, arsenic nan mechanisms uncovered tin perchance use to different enveloped viruses specified arsenic West Nile virus, Japanese encephalitis microorganism and Dengue virus," Kumar said.

Kumar's squad is utilizing a lipidomics attack to pinpoint lipid molecules possessing some proviral and antiviral properties, pinch nan overarching extremity of unearthing caller antiviral therapeutics.

The publication of this insubstantial underscores Wayne State's committedness to advancing technological knowledge and addressing pressing world wellness challenges. The interdisciplinary collaboration and innovative methodologies employed successful this investigation exemplify nan institution's dedication to excellence successful technological inquiry.

"Through nan innovative investigation squad that Dr. Kumar has established, they are astatine nan forefront of processing breakthroughs that will play a captious domiciled successful therapeutic interventions successful oculus abnormalities caused by nan Zika virus," said Ezemenari M. Obasi, Ph.D., vice president for investigation astatine Wayne State. "This study is an fantabulous illustration of really Wayne State's investigation is making discoveries that tin effect lives successful Detroit and astir nan world."

Source:

Journal reference:

Singh, S., et al. (2024). Targeting ABCG1 and SREBP-2 mediated cholesterin homeostasis ameliorates Zika microorganism induced ocular pathology. iScience. doi.org/10.1016/j.isci.2024.109088.