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My lab is interested in finding out how the virus stays in the liver for so long and what it does when it’s there.
The most stable form of the virus is its DNA because it’s very similar to our own DNA. If you think about your own DNA, you have it in each one of your cells for your entire life. It is super-stable and the virus mimics this.
There actually 2 different types of stable virus DNA and my group looks at both of them:
1) cccDNA - covalently closed circular DNA.
This is one you probably know of. If a cell has this form, it can easily produce new viruses; it’s basically a virus blueprint. The current drugs (Entecavir/Viread/Vemlidy) don’t actually target this blueprint, just the manufacturing of new viruses.
My group is looking at what the cell can do to get rid of it. One way that we’ve shown is just by dividing: if a cell splits, then our data suggests that the cccDNA is gone in the 2 cells that result. We’re now trying to understand why some cccDNA persists, even though the liver cells undergo a lot of division.
If we can understand these sorts of very basic ways that the cccDNA hangs around, then we will know exactly how to target it and hopefully get rid of the virus completely. This would mean a “complete cure”: you wouldn’t have to take medications for such a long time and there wouldn’t be a risk of the virus reactivating (there would be nothing to reactivate it from).
2) Integrated virus DNA
I’ve been working on super-interesting form of the virus since the very start of my career and it’s still puzzling scientists. Instead of making cccDNA, very rarely (1 in 10000 cells) the virus can jump into our own DNA. When it does this, it loses part of itself and it can’t produce new virus anymore. So why does the virus do this? We don’t know! (and whenever we don’t know, scientists get really interested).
What becomes important to human health is that even though it happens very rarely, it’s very commonly in liver cancers (most liver cancers have integrated virus DNA). So our research is trying to figure out why this is.
We’ve looked at if the integration itself causes cancer. My studies have shown that integration happens within days of an infection, but it takes many many decades for liver cancer to happen. So it doesn’t look like just because you have integration it directly causes cancer.
We think it might be something like integrations happen in cells that are more likely to become cancer (like if you have broken DNA, you are more likely to have integrations but also more likely to get cancer), though this is all very preliminary.
But it is important. If we understand what is actually driving liver cancer, we can develop ways to prevent it. Hep B is probably one of the better conditions for this cancer prevention to work, because the Hep B is easy to diagnose (blood test panels) and many times you have decades to intervene before cancer comes about.
Happy to take any questions about my research!
TT
