Plasma membranes host a plethora of proteins and glycans on their outer surface that are exploited by viruses to enter the cells. In this study, we have utilized this property to limit a viral infection using plasma membrane-derived vesicles. We show that plasma membrane-derived liposomes are prophylactically and therapeutically competent at preventing herpes simplex virus type-1 (HSV-1) infection. Plasma membrane liposomes derived from human corneal epithelial (HCE) cells, which are natural targets of HSV-1 infection, as well as Vero and Chinese hamster ovary (CHO) cells were used in this study. Our study clearly demonstrates that HCE and Vero-derived cellular liposomes, which express the viral entry-specific cell surface protein receptors, exhibit robust antiviral activity especially when compared to CHO-derived liposomes, which lack the relevant HSV-1 entry receptors. Further experimentation of the plasma membrane-derived liposomes with HSV type-2 (HSV-2) and pseudorabies virus yielded similar results, indicating strong potential for the employment of these liposomes to study viral entry mechanisms in a cell free-environment.

Herpes stromal keratitis (HSK) is a result of the inflammatory sequelae following primary and recurrent Herpes simplex virus type-1 (HSV-1) infections. This pathology is known to be mediated by immunopathogenic T cell responses against viral antigens, however most individuals infected with HSV-1 never exhibit signs of this immunopathology. Recent studies have identified the host restriction factor, optineurin (OPTN), as an inhibitor of viral spread in the central nervous system, protecting hosts from viral encephalopathy. In an HSV-1 corneal infection mouse model on OPTN knockout mice, we assess the contribution of OPTN to ameliorating the clinical manifestations of HSK. We identify that OPTN protects the host from loss of ocular and whisker sensitivity and opacification of the cornea. scRNA-seq of the trigeminal ganglion (TG) reveals that transcription changes to the peripheral neurons and immune cell populations drive the expression of Il-17A in CD4 and CD8 T cells, as well as increased infiltration of T cells into the TG. This leads to demyelination and the observed HSK pathology.