The idea of zoonotic diseases – that is, diseases that jump from animals to humans – is one we’ve all had to become familiar with over the past couple of years. After all, the leading theory on the origins of the COVID-19 pandemic suggests that it was a bat disease before it infected humans. Before that there was swine flu, which came from – you guessed it – swine, and bird flu, which came from a similarly eponymous source.
So naturally, it’s in our interest to try to figure out where the next zoonotic disease might come from. A new study, currently available on the Cell Press preprint server while it undergoes peer review, has taken a look at one concerning possibility: a new kind of ebolavirus called Bombali virus, found – for the moment – in bats.
There are six known species of ebolavirus, but the most famous is probably, well, the Ebola virus. For 40 years, this disease lurked around East and Central Africa, every so often causing outbreaks that proved too fatal to become large-scale. But in 2014, Ebola went mainstream, killing thousands.
Up to two-thirds of people who caught the Ebola virus between 2014 and 2016 died from the disease, and other ebolaviruses are similarly deadly. So even though Bombali virus hasn’t yet made it into humans, the researchers wanted to get an idea of how we could cope with an outbreak if it did manage to break out.
Of course, the first thing to check is whether the disease can actually infect humans – otherwise there’s no need to worry – so the researchers took a look at how Bombali virus would interact with human immune systems. After first isolating the virus through a process of reverse genetics, they then exposed it to human macrophages – white blood cells which “eat” invading organisms like viruses.
Like Ebola, the Bombali virus “infected human cells and primary human macrophages,” the authors report, and was able to “efficiently … enter cells” using the same mechanism as its viral cousin. Although both diseases were shown to infect a similar number of macrophages, the researchers found that they altered cells’ RNA in different ways to achieve replication.
And while both induced immune reactions from the blood cells, only Ebola, and not Bombali, prompted an antiviral response to be deployed.
Using a technique known as principal component analysis, the researchers discovered that some of the main differences in the genomic sequence of the two diseases related to genes which encode inflammatory cytokines, chemokines, and interferon-stimulating genes – all important parts of the body’s immune response.
That’s the bad news – now for the good. The researchers were also on the lookout for a potential treatment of Bombali, and, since it’s “morphologically indistinguishable from Ebola virus,” they report, they started there. How would Bombali virus respond to current Ebola treatments?
In recent years, two therapies have emerged as potential candidates for Ebola therapies, and they may sound familiar: the broad-spectrum antiviral drug remdesivir, and monoclonal antibody therapies.
While both of these therapies have proved useful against Ebola, not all held up so well against Bombali. Remdesivir did well: when administered at the same dosage as for Ebola it helped suppress virus replication and prevent infection. So did some – but not all – of the monoclonal antibody therapies. That’s because different monoclonal antibodies attack different parts of the virus: it seems the two ebolaviruses, while similar, had enough variation between them to render some of the therapies useless.
While the prospect of yet another new and potentially fatal disease being unleashed on the world is hardly a welcome one, studies like this are a crucial way of preparing ourselves for if the worst should happen. We may never need to know which antiviral drugs and which particular monoclonal antibodies work against Bombali virus – but if we do, we’re now that little bit better armed to fight this potentially devastating disease.