Anti-heparan Sulfate Peptides That Block Herpes Simplex Virus Infection in Vivo

• DOI: 10.1074/jbc.m110.201103
• Publication Date: 2011-05-20T00:47:07Z
• Authors: Vaibhav Tiwari; Jian Liu; Tibor Valyi-Nagy; Deepak Shukla
• Keywords: Herpesvirus glycoprotein B

Heparan sulfate (HS) and its highly modified form, 3-O-sulfated heparan (3-OS HS), contribute strongly to herpes simplex virus type-1 (HSV-1) infection in vitro. Here we report results from a random M13-phage display library screening isolate 12-mer peptides that bind specifically HS, 3-OS block HSV-1 entry. The identified representative candidates two-different groups of anti-HS with high positive charge densities. Group 1, represented by G1 peptide (LRSRTKIIRIRH), belongs class alternating charges (XRXRXKXXRXRX), group 2, G2 (MPRRRRIRRRQK), shows repetitive (XXRRRRXRRRXK). Viral entry glycoprotein D binding assays together fluorescent microscopy data indicated both were potent blocking into primary cultures human corneal fibroblasts CHO-K1 cells transiently expressing different receptors. Interestingly, isolated against HS displayed wider ability inhibit clinically relevant strains some divergent members herpesvirus family including cytomegalovirus herpesvirus-8. To identify functional residues within G2, performed point mutations alanine-scanning mutagenesis. Several arginine lysine needed for anti-HSV-1 activity, suggesting the importance positively charged virus-cell virus-induced membrane fusion. In vivo administration or as prophylactic eye drop completely blocked spread mouse cornea evident immunohistochemistry. This result also highlights an significance during ocular infection.