Abstract
HSV glycoprotein K (gK) is an essential herpes protein that contributes to enhancement of eye disease. We previously reported that gK binds to signal peptide peptidase (SPP) and that depletion of SPP reduces HSV-1 infectivity in vivo. To determine the therapeutic potential of blocking gK binding to SPP on virus infectivity and pathogenicity, we mapped the gK binding site for SPP to a 15mer peptide within the amino-terminus of gK. This 15mer peptide reduced infectivity of three different virus strains in vitro as determined by plaque assay, FACS, and RT-PCR. Similarly, the 15mer peptide reduced ocular virus replication in both BALB/c and C57BL/6 mice and also reduced levels of latency and exhaustion markers in infected mice when compared with control treated mice. Addition of the gK-15mer peptide also increased the survival of infected mice when compared with control mice. These results suggest that blocking gK binding to SPP using gK peptide may have therapeutic potential in treating HSV-1-associated infection.
Highlights
HSV-1-induced corneal scarring (CS), broadly referred to as herpes stromal keratitis (HSK), is the leading cause of infectious blindness in developed countries [1,2]
We reported that glycoprotein K (gK) binding to signal peptide peptidase (SPP) is important for virus infectivity in vitro and in vivo
We demonstrated that gK binds to signal peptide peptidase (SPP) and that this binding is essential for HSV-1 infectivity in vitro and in vivo [8,9,10]
Summary
HSV-1-induced corneal scarring (CS), broadly referred to as herpes stromal keratitis (HSK), is the leading cause of infectious blindness in developed countries [1,2]. Effect of blocking gK binding to SPP on herpes infectivity collection and analysis, decision to publish, or preparation of the manuscript
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