Abstract
Purpose :
We previously reported that binding of HSV-1 glycoprotein K (gK) to signal peptide peptidase (SPP) is required for virus infectivity. The goal of this study was to map the gK binding region to SPP and to determine if blocking gK binding to SPP using gK peptides reduces HSV-1 primary infection, latency-reactivation, and corneal scarring.
Methods :
The gK domain binding to SPP was mapped using co-immunoprecipitation assays. Effect of this peptide, which we call gK4, on virus infectivity was determined by plaque assay, FACS and RT-PCR. The effect of ocular administration of gK4 on ocular HSV-1 replication was evaluated in BALB/c and C57BL/6 mice.
Results :
Using a combination of gK fragments and gK peptides the binding domain of gK to SPP was mapped to 5 amino acids. HSV-1 replication in Vero cells was significantly inhibited by gK4 peptide treatment compared to control peptide. BALB/c mice treated with gK4 peptide as eye drops showed significantly less virus replication in the tear film and significantly fewer viral transcripts in the cornea and trigeminal ganglia during primary ocular infection with virulent HSV-1 strain McKrae. Survival in BALB/c mice was improved after treatment with gK4 peptide. Similar results were obtained following treatment of C57BL/6 mice with gK4 peptide.
Conclusions :
Our results suggest that the gK4 peptide significantly reduced virus replication both in vitro and in vivo. Thus, gK4 peptide may have therapeutic potential to control ocular HSV-1 infections.
This is a 2021 ARVO Annual Meeting abstract.