In vitro inhibition of monkeypox virus production and spread by Interferon-β

Sara C Johnston,John H Connor,Gordon Ruthel,Lisa E Hensley,Kenny L Lin,Arthur Goff

doi:10.1186/1743-422x-9-5

Abstract

BackgroundThe Orthopoxvirus genus contains numerous virus species that are capable of causing disease in humans, including variola virus (the etiological agent of smallpox), monkeypox virus, cowpox virus, and vaccinia virus (the prototypical member of the genus). Monkeypox is a zoonotic disease that is endemic in the Democratic Republic of the Congo and is characterized by systemic lesion development and prominent lymphadenopathy. Like variola virus, monkeypox virus is a high priority pathogen for therapeutic development due to its potential to cause serious disease with significant health impacts after zoonotic, accidental, or deliberate introduction into a naïve population.ResultsThe purpose of this study was to investigate the prophylactic and therapeutic potential of interferon-β (IFN-β) for use against monkeypox virus. We found that treatment with human IFN-β results in a significant decrease in monkeypox virus production and spread in vitro. IFN-β substantially inhibited monkeypox virus when introduced 6-8 h post infection, revealing its potential for use as a therapeutic. IFN-β induced the expression of the antiviral protein MxA in infected cells, and constitutive expression of MxA was shown to inhibit monkeypox virus infection.ConclusionsOur results demonstrate the successful inhibition of monkeypox virus using human IFN-β and suggest that IFN-β could potentially serve as a novel safe therapeutic for human monkeypox disease.

Highlights

The Orthopoxvirus genus contains numerous virus species that are capable of causing disease in humans, including variola virus, monkeypox virus, cowpox virus, and vaccinia virus
HeLa cells that were pre-treated for 24 hours (h) before infection with increasing concentrations of IFN-b (0-5000 units [U]/ml) were infected with monkeypox virus (MPXV)-Zaire at a high multiplicity of infection (MOI)
Titration results indicated that MPXV was susceptible to inhibition by IFN-b with concentrations as low as 600 U/ml, and an optimal approximately 91% reduction was seen with 2000 U/ml of IFN-b (Figure 1a)

Summary

Introduction

The Orthopoxvirus genus contains numerous virus species that are capable of causing disease in humans, including variola virus (the etiological agent of smallpox), monkeypox virus, cowpox virus, and vaccinia virus (the prototypical member of the genus). The Orthopoxvirus genus of the family Poxviridae contains a number of pathogens known to infect humans, including variola virus (VARV, the causative agent of smallpox), cowpox virus, camelpox virus, vaccinia virus, and monkeypox virus (MPXV). VARV, the etiological agent of smallpox, causes an acute, systemic lesional disease with a mortality rate of approximately 30% [5,6]. VARV is not the only member of the Orthopoxvirus genus that causes severe disease in humans and has the potential for development as a biological weapon. The global eradication of smallpox and the subsequent cessation of smallpox vaccination in 1980 allowed for the emergence of another lethal zoonotic disease, monkeypox

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