Inhibition of Vaccinia virus entry by a broad spectrum antiviral peptide

Journal Article · Fri Jun 05 04:00:00 EDT 2009 · Virology

DOI:https://doi.org/10.1016/j.virol.2009.03.023· OSTI ID:21357519

Altmann, S E; Jones, J C ^[1]; Schultz-Cherry, S ^[1]

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1. Microbiology Doctoral Training Program, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706 (United States)

Concerns about the possible use of Variola virus, the causative agent of smallpox, as a weapon for bioterrorism have led to renewed efforts to identify new antivirals against orthopoxviruses. We identified a peptide, EB, which inhibited infection by Vaccinia virus with an EC{sub 50} of 15 muM. A control peptide, EBX, identical in composition to EB but differing in sequence, was inactive (EC{sub 50} > 200 muM), indicating sequence specificity. The inhibition was reversed upon removal of the peptide, and EB treatment had no effect on the physical integrity of virus particles as determined by electron microscopy. Viral adsorption was unaffected by the presence of EB, and the addition of EB post-entry had no effect on viral titers or on early gene expression. The addition of EB post-adsorption resulted in the inhibition of beta-galactosidase expression from an early viral promoter with an EC{sub 50} of 45 muM. A significant reduction in virus entry was detected in the presence of the peptide when the number of viral cores released into the cytoplasm was quantified. Electron microscopy indicated that 88% of the virions remained on the surface of cells in the presence of EB, compared to 37% in the control (p < 0.001). EB also blocked fusion-from-within, suggesting that virus infection is inhibited at the fusion step. Analysis of EB derivatives suggested that peptide length may be important for the activity of EB. The EB peptide is, to our knowledge, the first known small molecule inhibitor of Vaccinia virus entry.

• OSTI ID: 21357519
• Journal Information: Virology, Journal Name: Virology Journal Issue: 2 Vol. 388; ISSN VIRLAX; ISSN 0042-6822
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ADSORPTION
CELL CONSTITUENTS
CYTOPLASM
ELECTRON MICROSCOPY
ENZYMES
GALACTOSIDASE
GENES
GLYCOSYL HYDROLASES
HYDROLASES
INHIBITION
MICROORGANISMS
MICROSCOPY
O-GLYCOSYL HYDROLASES
ORGANIC COMPOUNDS
PARASITES
PEPTIDES
PROTEINS
SORPTION
VACCINIA VIRUS
VIRUSES