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Role of tear exosomes in the spread of herpes simplex virus type 1 in recurrent herpes simplex keratitis

Eye volume 37, pages 3180–3185 (2023)Cite this article

Subjects

Abstract

Background

Herpes simplex keratitis (HSK) is the most common but serious infectious keratitis with high recurrence. It is predominantly caused by herpes simplex virus type 1 (HSV-1). The spread mechanism of HSV-1 in HSK is not entirely clear. Multiple publications indicate that exosomes participate in the intercellular communication process during viral infections. However, there is rare evidence that HSV-1 spreads in HSK by exosomal pathway. This study aims to investigate the relationship between the spread of HSV-1 and tear exosomes in recurrent HSK.

Methods

Tear fluids collected from total 59 participants were included in this study. Tear exosomes were isolated by ultracentrifugation, then identified by silver staining and western blot. The size was determined by dynamic light scattering (DLS). The viral biomarkers were identified by western blot. The cellular uptake of exosomes was studied using labelled exosomes.

Results

Tear exosomes were indeed enriched in tear fluids. Collected exosomes own normal diameters consistent with related reports. The exosomal biomarkers existed in tear exosomes. Labelled exosomes were successfully taken up by human corneal epithelial cells (HCEC) in large numbers in a short time. After cellular uptake, HSK biomarkers were detectable by western blot in infected cells.

Conclusions

Tear exosomes should be the latent sites of HSV-1 in recurrent HSK and might be involved in the spread of HSV-1. Besides, this study verifies HSV-1 genes can be indeed transferred between cells by exosomal pathway, providing new inspiration for the clinical intervention and treatment as well as the drug discovery of recurrent HSK.

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Fig. 1: Identification of exosome biomarkers in precipitate and supernatant isolated from tear fluids.
Fig. 2: Hydrodynamic particle size of tear exosomes.
Fig. 3: Identification of tear exosome biomarkers for classical HSK.
Fig. 4: Confocal laser scanning micrograph of HCEC co-incubated with tear exosomes.
Fig. 5: Identification of HSK biomarkers in infected cells.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was financially supported by the Science & Technology Program of Wenzhou (Y20190169, Y2020204), Department of Health of Zhejiang Province (2022KY216).

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Authors and Affiliations

  1. National Engineering Research Center of Ophthalmology and Optometry, School of Biomedical Engineering, School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China

    Huiying Huang, Sihao Liu, Xia Zhao, Peiyi Zhao, Qingqing Jia, Huixiang Ma & Quankui Lin

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  1. Huiying Huang
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  2. Sihao Liu
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Contributions

HH contributed to experiments design and performance, data analysis and interpretation, and the original draft writing; SL and XZ contributed to sample collection; PZ and QJ contributed to sample preparation; HM contributed to participant recruitments and sample collection; QL contributed to resources, supervision, writing reviewing and editing.

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Correspondence to Huixiang Ma or Quankui Lin.

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Huang, H., Liu, S., Zhao, X. et al. Role of tear exosomes in the spread of herpes simplex virus type 1 in recurrent herpes simplex keratitis. Eye 37, 3180–3185 (2023). https://doi.org/10.1038/s41433-023-02473-4

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