The virucidal EB peptide protects host cells from herpes simplex virus type 1 infection in the presence of serum albumin and aggregates proteins in a detergent-like manner.
The linear cationic amphiphilic EB peptide, derived from the FGF4 signal sequence, was previously shown to be virucidal and to block herpes simplex type I (HSV-1) entry (H. Bultmann, J. S. Busse, and C. R. Brandt, J. Virol. 75:2634-2645, 2001). Here we show that cells treated with EB (RRKKAAVALLPAVLLALLAP) for less than 5 min are also protected from infection with HSV-1. Though protection was lost over a period of 5 to 8 h, it was reinduced as rapidly as during the initial treatment. Below a 20 μM concentration of EB, cells gained protection in a serum-dependent manner, requiring bovine serum albumin (BSA) as a cofactor. Above 40 μM, EB coprecipitated with BSA under hypotonic conditions. Coprecipitates retained antiviral activity and released active peptide. NaCl (≥0.3 M) blocked coprecipitation without interfering with antiviral activity. As shown for β-galactosidase, EB below 20 μM acted as an enzyme inhibitor, whereas above 40 to 100 μM EB, β-galactosidase was precipitated as was BSA or other unrelated proteins. Pyrene fluorescence spectroscopy revealed that in the course of protein aggregation, EB acted like a cationic surfactant and self associated in a process resembling micelle formation. Both antiviral activity and protein aggregation did not depend on stereospecific EB interactions but depended strongly on the sequence of the peptide's hydrophobic tail. EB resembles natural antimicrobial peptides, such as melittin, but when acting in a nonspecific detergent-like manner, it primarily seems to target proteins.
Bultmann
Hermann
H
Department of Ophthalmology & Visual Sciences, University of Wisconsin, Madison, Wisconsin 53706, USA.
Girdaukas
Gary
G
Kwon
Glen S
GS
Brandt
Curtis R
CR
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000627:therapeutic use*; D002417:Cattle; D002460:Cell Line; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D006561:Herpes Simplex / Q000517:prevention & control* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000472:pathogenicity*; D006801:Humans; D010455:Peptides / Q000737:chemistry / Q000627:therapeutic use*; D012709:Serum Albumin / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013696:Temperature; D014709:Vero Cells
D000998:Antiviral Agents; D010455:Peptides; D012709:Serum Albumin