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  • Alex Cloherty

Fatty McFat... Virus?

Here on Microbial Mondays, we have talked a lot about proteins and nucleic acids like RNA and DNA. However, proteins and nucleic acids are by no means the only important molecules in cells – we have two whole other major classes of biological molecules: sugars and fats! You might be used to thinking of sugar as just the junk in your chocolate bar, or fat as just the behemoth in London's sewer, but there's far more going on than that.

Today, I'd like to give a shout out to fat by diving into the world of lipids droplets (lipid more or less means fat). Lipid droplets are cellular organelles (tiny cell-sized organs) that we used to think were only used for storing fats. However, these organelles keep surprising scientists by turning out to have new functions. This is where we tie in to the Microbial part of Microbial Mondays. A lot of the intriguing functions of lipid droplets were discovered because viruses, bacteria, fungi, and a variety of parasites hijack these organelles for their own use. Today, I'd like to give you an overview of not only the importance of fat for us humans, but also for one of the many lipid-loving bugs that infect us: Hepatitis C virus.

You might already know that the HepC virus attacks the liver of infected patients, and maybe you also knew that it can cause non-alcoholic fatty liver disease. What you might not have known is why. This question sheds light on the importance of fats for not only the virus, but also for us humans. When a human cell is infected with HepC, one of the first things the virus does is completely restructure the cell's lipid architecture. If the cell looks like a tasteful garden before infection, HepC turns it into a hedge maze, with all the hedges being made of fat.

The HepC virus upregulates its host cell's production of fat, and hyper-organizes those newly made fats into a hedge maze sprinkled with lipid droplets, for a few different reasons. Some of the best-understood reasons for this obsessive organization of lipids are 1) to hide the virus in a maze of lipids to confuse the host immune system, and 2) to make little fatty virus rooms for the HepC to replicate itself in. These little fatty virus rooms keep all the different bits of the virus together in one place so that they can be properly formed into new, baby HepC viruses. You can compare this to an arts and crafts room: it's much more efficient to put together a new project if all of your art supplies are in one place, rather than spread out all over the neighbourhood. Altogether, this huge increase in the fats in cells due to HepC infection leads to one of the major outcomes of HepC, fatty liver disease.

After the HepC virus has started to put itself together, it still isn't quite done with lipid droplets and their associated fats. When the newly-made baby HepC viruses leave their host cell, to eventually go on and infect new host cells, they actually coat themselves in a layer of stolen fat. In the bloodstream, HepC circulates as "lipoviroparticles", i.e. fatty-virus-thingies. Researchers think that this fat coating helps HepC hide from and manipulate the human immune system to the advantage of the virus.

All this fat-hijacking is so important to the the virus, that eliminating lipid droplets in the host cell totally prevents the production of infectious HepC virus. However, besides identifying new ways to treat HepC, this research into the role of fats and lipid droplets during viral infection also made us notice the importance of fats in everyday life. We noticed that cells get pretty messed up if HepC makes too much fat, which illustrates the importance of the normal cycle of fat production and then break-down. We also saw how lipid droplets help keep all the different bits of HepC together in one place, which made us notice how lipid droplets also help keep normal human proteins organized. And finally, we discovered that the coating of fat helps HepC manipulate the human immune system, which showed us that fat is important in normal, healthy immune signalling. And when we discover the next new function of fat for Hepatitis C, I'm sure that will draw our attention to a new and exciting function of fat for healthy human cells. All in all, this is another reason why studying microbes is so important: learning about how these bugs hijack our systems teaches us about ourselves!

That's all for this week - until next time, love those lipids!

- Alex

P.S. For more reading, check out...

Henne, W. M., Reese, M. L., & Goodman, J. M. (2018). The assembly of lipid droplets and their roles in challenged cells. The EMBO Journal, e98947.

Paul, D., Madan, V., & Bartenschlager, R. (2014). Hepatitis C virus RNA replication and assembly: Living on the fat of the land. Cell Host and Microbe, 16(5), 569–579.

Popescu, C.-I., Riva, L., Vlaicu, O., Farhat, R., Rouillé, Y., & Dubuisson, J. (2014). Hepatitis C Virus Life Cycle and Lipid Metabolism. Biology, 3(4), 892–921.

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