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Journal of Virology, March 2001, p. 2634-2645, Vol. 75, No. 6
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.6.2634-2645.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Modified FGF4 Signal Peptide Inhibits Entry of Herpes Simplex Virus Type 1

Hermann Bultmann,1 James S. Busse,2 and Curtis R. Brandt1,3,*

Department of Ophthalmology and Visual Sciences1 and Department of Medical Microbiology and Immunology,3 Medical School, and Department of Biochemistry, College of Agriculture and Life Sciences,2 University of Wisconsin---Madison, Madison, Wisconsin

Received 31 July 2000/Accepted 14 December 2000

Entry of herpes simplex virus type 1 (HSV-1) into host cells occurs through fusion of the viral envelope with the plasma membrane and involves complex and poorly understood interactions between several viral and cellular proteins. One strategy for dissecting the function of this fusion machine is through the use of specific inhibitors. We identified a peptide with antiviral activity that blocks HSV-1 infection at the entry stage and during cell-to-cell spreading. This peptide (called EB for "entry blocker") consists of the FGF4 signal sequence with an RRKK tetramer at the amino terminus to improve solubility. The activity of EB depends exclusively but not canonically on the signal sequence. Inhibition of virus entry (hrR3) and plaque formation (KOS) strongly depend on virus concentrations and serum addition, with 50% inhibitory concentrations typically ranging from 1 to 10 µM. Blocking preadsorbed virus requires higher EB concentrations. Cytotoxic effects (trypan blue exclusion) are first noted at 50 µM EB in serum-free medium and at >= 200 µM in the presence of serum. EB does not affect gC-dependent mechanisms of virus attachment and does not block virus attachment at 4°C. Instead, EB directly interacts with virions and inactivates them irreversibly without, however, disrupting their physical integrity as judged by electron microscopy. At subvirucidal concentrations, EB changes the adhesive properties of virions, causing aggregation at high virus concentrations. This peptide may be a useful tool for studying viral entry mechanisms.

* Corresponding author. Mailing address: Department of Ophthalmology and Visual Sciences, University of Wisconsin, 1300 University Ave., 6630 MSC, Madison, WI 53706-1532. Phone: (608) 262-8054. Fax: (608) 262-0479. E-mail: crbrandt{at}facstaff.wisc.edu.

Journal of Virology, March 2001, p. 2634-2645, Vol. 75, No. 6
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.6.2634-2645.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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