Published in Research

Therapeutic may resolve Zika virus-related ocular infections

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4 min read

Findings from a recent study published in iScience identified two targets in the cholesterol pathway that contribute to Zika virus (ZIKV)-induced ocular pathology during pregnancy that could be used to develop antiviral therapies.

Give me some background on ZIKV.

ZIKV is a mosquito-borne viral infection that gained international attention during a large outbreak in Brazil from 2015-2016, wherein the World Health Organization (WHO) declared it a public health emergency.

Note: There are currently no approved antiviral therapies or vaccines for ZIKV.

Bring in ZIKV-induced ocular complications.

One of the most concerning aspects of ZIKV is its association with congenital ZKV syndrome—when babies are born to infected mothers during pregnancy.

This syndrome can lead to severe neurological and ocular abnormalities, such as:

  • Microcephaly
  • Brain damage
  • Retinal lesions
  • Hemorrhagic retinopathy
  • Optic neuritis
  • Hypoplasia of the optic nerve

Now talk about the study.

A research team from the Wayne State University School of Medicine conducted in vitro and in vivo transcriptomic analyses of ZIKV-infected retinal pigment epithelium (RPE) cells.

Remind me what transcriptomics is.

Transcriptomics is the study of the transcriptome, which is the full range of messenger RNA (mRNA) molecules expressed under specific circumstances or in a specific cell.

As RNA sequences mirror the DNA sequence that they were transcribed from, transcriptomic analyses allow researchers to determine when and where each gene is switched on or off in the cells and tissues of an organism.

Why study RPE cells?

Systemic viral infections cause vision impairment by disrupting the blood-retina barrier (BRB), leading to the infiltration of immune cells and intraocular inflammation.

Consequently, RPE cells forming the outer BRB are the primary target of blood-borne viral pathogens.

Findings?

Investigators discovered that ZIKV-induced ocular pathology is caused by significant alterations in the cholesterol pathway.

These alterations are primarily caused by two molecules involved in cholesterol metabolism:

  • ATP-binding cassette transporter G1 (ABCG1)
  • Sterol response element binding protein 2 (SREBP-2)

What is the impact of ABCG1 and SREBP-2 on ZIKV?

The researchers found that increased ABCG1 activity—mediated by liver X receptors (LXRs)—led to reduced ZIKV replication.

Meanwhile, inhibition of SREBP-2 decreased viral replication by lowering cholesterol levels.

Take home.

This study highlights the dynamic relationship between cholesterol metabolism and ZIKV infection in the eye.

Per the study authors, the findings suggest that targeting cholesterol metabolism components—such as ABCG1’s antiviral effect and SREBP-2’s proviral effects—in ocular ZIKV could lead to the development of antiviral therapies.

Next steps?

The mechanisms that cause ZIKV-induced ocular pathology uncovered by the research team could potentially be applied to other enveloped viruses, such as West Nile virus, Japanese encephalitis virus, and Dengue virus.

Additionally, this same research team is currently using lipidomics to identify lipid molecules that contain both proviral and antiviral properties to discover other novel antiviral therapeutics.

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