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

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.

Vaccinia virus and Cowpox virus are not susceptible to the interferon-induced antiviral protein MxA

“…MxA is relocalized around DNA-containing viral factories in ASFV-infected cells, which represent virus assembly sites. In contrast, in MPX infected cells, MxA was shown to colocalize partially with the virus wrapping area, but not with viral factories [10]. Our results are reminiscent of the distribution reported for ASFV infection since partial colocalization with the viral factories area was detected.…”

Mx GTPases: dynamin-like antiviral machines of innate immunity

“…At present, the role of membrane binding for Mx action is still poorly understood. It may be essential for inhibiting viruses that rely on membranes for replication, such as bunyaviruses, positive-strand RNA viruses, poxviruses, and African swine fever virus (ASFV) [56][57][58]. It also may play a role in protecting Mx from degradation and stabilize the intracellular Mx pool after induction by IFN [59].…”

An evolutionary perspective on the broad antiviral specificity of MxA

“…For example, MxA inhibits the hepadnavirus hepatitis B virus (HBV) [9] via the hepatitis B core antigen protein (HBcAg) [10]. MxA has also been reported to restrict large double-stranded DNA viruses including the orthopoxvirus monkeypox [11] and the poxvirus-like Asfarvirus African swine fever virus (ASFV) [12]; for these viruses MxA targets are unknown. Taken together, these studies show that MxA interacts with highly divergent proteins across a diversity of viral families.…”