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Antiviral activity of the EB peptide against zoonotic poxviruses.

Altmann SE, Brandt CR, Jahrling PB, Blaney JE - Virol. J. (2012)

Bottom Line: The EB peptide is a 20-mer that was previously shown to have broad spectrum in vitro activity against several unrelated viruses, including highly pathogenic avian influenza, herpes simplex virus type I, and vaccinia, the prototypic orthopoxvirus.A scrambled peptide had no inhibitory activity against either virus.Monkeypox was also inhibited in vitro by EB, but at the attachment stage of infection.

View Article: PubMed Central - HTML - PubMed

Affiliation: Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. altmannse@niaid.nih.gov

ABSTRACT

Background: The EB peptide is a 20-mer that was previously shown to have broad spectrum in vitro activity against several unrelated viruses, including highly pathogenic avian influenza, herpes simplex virus type I, and vaccinia, the prototypic orthopoxvirus. To expand on this work, we evaluated EB for in vitro activity against the zoonotic orthopoxviruses cowpox and monkeypox and for in vivo activity in mice against vaccinia and cowpox.

Findings: In yield reduction assays, EB had an EC50 of 26.7 μM against cowpox and 4.4 μM against monkeypox. The EC50 for plaque reduction was 26.3 μM against cowpox and 48.6 μM against monkeypox. A scrambled peptide had no inhibitory activity against either virus. EB inhibited cowpox in vitro by disrupting virus entry, as evidenced by a reduction of the release of virus cores into the cytoplasm. Monkeypox was also inhibited in vitro by EB, but at the attachment stage of infection. EB showed protective activity in mice infected intranasally with vaccinia when co-administered with the virus, but had no effect when administered prophylactically one day prior to infection or therapeutically one day post-infection. EB had no in vivo activity against cowpox in mice.

Conclusions: While EB did demonstrate some in vivo efficacy against vaccinia in mice, the limited conditions under which it was effective against vaccinia and lack of activity against cowpox suggest EB may be more useful for studying orthopoxvirus entry and attachment in vitro than as a therapeutic against orthopoxviruses in vivo.

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EB reduces gene expression in CPXV and MPXV. Triplicate wells of BSC-1 cells were infected with recombinant CPXV (A) or recombinant MPXV (B) expressing GFP under the control of an artificial early/late promoter at a m.o.i. of 1 in the presence of EB for 1 hr at 4°C, rinsed 3 times, and treated with peptide-containing media. Twenty-four hours post-infection, GFP intensity was measured at 520 nm. Data are representative of three independent assays.
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Figure 2: EB reduces gene expression in CPXV and MPXV. Triplicate wells of BSC-1 cells were infected with recombinant CPXV (A) or recombinant MPXV (B) expressing GFP under the control of an artificial early/late promoter at a m.o.i. of 1 in the presence of EB for 1 hr at 4°C, rinsed 3 times, and treated with peptide-containing media. Twenty-four hours post-infection, GFP intensity was measured at 520 nm. Data are representative of three independent assays.

Mentions: EB was next tested for its ability to reduce gene expression during CPXV and MPXV infections (Figure 2). BSC-1 cells were infected with recombinant CPXV or MPXV expressing GFP under the control of a synthetic early/late promoter in the presence of increasing concentrations of EB. The EB peptide reduced GFP expression by both viruses, with an EC50 of 26.7 μM against CPXV and 27.6 μM against MPXV, indicating that EB acted upstream of gene expression to inhibit both viruses.


Antiviral activity of the EB peptide against zoonotic poxviruses.

Altmann SE, Brandt CR, Jahrling PB, Blaney JE - Virol. J. (2012)

EB reduces gene expression in CPXV and MPXV. Triplicate wells of BSC-1 cells were infected with recombinant CPXV (A) or recombinant MPXV (B) expressing GFP under the control of an artificial early/late promoter at a m.o.i. of 1 in the presence of EB for 1 hr at 4°C, rinsed 3 times, and treated with peptide-containing media. Twenty-four hours post-infection, GFP intensity was measured at 520 nm. Data are representative of three independent assays.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3275487&req=5

Figure 2: EB reduces gene expression in CPXV and MPXV. Triplicate wells of BSC-1 cells were infected with recombinant CPXV (A) or recombinant MPXV (B) expressing GFP under the control of an artificial early/late promoter at a m.o.i. of 1 in the presence of EB for 1 hr at 4°C, rinsed 3 times, and treated with peptide-containing media. Twenty-four hours post-infection, GFP intensity was measured at 520 nm. Data are representative of three independent assays.
Mentions: EB was next tested for its ability to reduce gene expression during CPXV and MPXV infections (Figure 2). BSC-1 cells were infected with recombinant CPXV or MPXV expressing GFP under the control of a synthetic early/late promoter in the presence of increasing concentrations of EB. The EB peptide reduced GFP expression by both viruses, with an EC50 of 26.7 μM against CPXV and 27.6 μM against MPXV, indicating that EB acted upstream of gene expression to inhibit both viruses.

Bottom Line: The EB peptide is a 20-mer that was previously shown to have broad spectrum in vitro activity against several unrelated viruses, including highly pathogenic avian influenza, herpes simplex virus type I, and vaccinia, the prototypic orthopoxvirus.A scrambled peptide had no inhibitory activity against either virus.Monkeypox was also inhibited in vitro by EB, but at the attachment stage of infection.

View Article: PubMed Central - HTML - PubMed

Affiliation: Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. altmannse@niaid.nih.gov

ABSTRACT

Background: The EB peptide is a 20-mer that was previously shown to have broad spectrum in vitro activity against several unrelated viruses, including highly pathogenic avian influenza, herpes simplex virus type I, and vaccinia, the prototypic orthopoxvirus. To expand on this work, we evaluated EB for in vitro activity against the zoonotic orthopoxviruses cowpox and monkeypox and for in vivo activity in mice against vaccinia and cowpox.

Findings: In yield reduction assays, EB had an EC50 of 26.7 μM against cowpox and 4.4 μM against monkeypox. The EC50 for plaque reduction was 26.3 μM against cowpox and 48.6 μM against monkeypox. A scrambled peptide had no inhibitory activity against either virus. EB inhibited cowpox in vitro by disrupting virus entry, as evidenced by a reduction of the release of virus cores into the cytoplasm. Monkeypox was also inhibited in vitro by EB, but at the attachment stage of infection. EB showed protective activity in mice infected intranasally with vaccinia when co-administered with the virus, but had no effect when administered prophylactically one day prior to infection or therapeutically one day post-infection. EB had no in vivo activity against cowpox in mice.

Conclusions: While EB did demonstrate some in vivo efficacy against vaccinia in mice, the limited conditions under which it was effective against vaccinia and lack of activity against cowpox suggest EB may be more useful for studying orthopoxvirus entry and attachment in vitro than as a therapeutic against orthopoxviruses in vivo.

Show MeSH
Related in: MedlinePlus