Inhibiting PP2A-B56 to Suppress Ebola Virus Transcription and Infection

Ebola Virus Host Factor Therapeutic TargetResearchers from the University of Copenhagen and Phillips Universität Marburg have found a new target for inhibiting Ebola virus from copying itself to produce more infection in a host.

‘When the Ebola virus enters the human cell, its only purpose is to copy itself, fast. First it must copy all its proteins, then its genetic material. But by inhibiting a specific enzyme we rob the Ebola virus of its ability to copy itself. And that may potentially prevent an Ebola infection from spreading’, says Professor Jakob Nilsson from the Novo Nordisk Foundation Center for Protein Research.

The virus uses the host factor enzyme PP2A-B56 to start producing proteins. If the researchers switch off PP2A-B56, the virus’ ability to copy itself and produce more infection is never ‘switched on’.

‘When we inhibit the PP2A-B56 enzyme, we remove the first link in a long process, which ends with Ebola spreading. And we can tell that it works. The Ebola infection in cell cultures where we have inhibited the PP2A-B56 enzyme is 10 times smaller after 24 hours compared to infections where we have not inhibited this enzyme’, says Jakob Nilsson.

But because the researchers have so far focused on cell cultures, there more work is needed before their results can be used to treat people infected with Ebola. Initially the researchers hope to be able to test it on animals and, in the long term, develop a drug that inhibits the relevant enzyme.

The research may prove useful for other filoviruses, such as Lloviu virus and Marburg virus.

Read more at Molecular Cell: The Ebola Virus Nucleoprotein Recruits the Host PP2A-B56 Phosphatase to Activate Transcriptional Support Activity of VP30.

Source: University of Copenhagen, edited for context and format by Global Biodefense.

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