Want to Turn a Moth Into Zombie Soup? Just Add Sugar (and a Virus)
Part of learning about biochemistry and molecular biology is realising that the same molecule can mean different things in different contexts. This is one issue with the field of pseudo-medicine (also known as "alternative medicine", but I think that gives it too much credit) - chemicals are demonised based purely on one context in which we can encounter them. Formaldehyde in vaccines? You definitely shouldn't drink any, but your body metabolically produces far more of the substance naturally every day than you would ever get from a single shot. Acidic diets? Don't spill concentrated hydrochloric acid on yourself, but lemon juice is pretty safe to ingest, and it's far more acidic than soft drinks. Biochemistry is rarely simple.
The complexity of chemical interactions in biological systems, however, is what makes this area of science so fascinating. By studying the various different roles the same molecule can have, even within a single cell, you unlock parts of biology you'd probably never even thought of before. Well, at least that's the case with me.
This post comes out of research I was doing the other day about insect viruses; my supervisor found a potential link between viral resistance and the gene family I'm studying, so I thought I would take a closer look. Turns out a lot of science is about reading things - who would have thought? And this particular area involves a novel use of sugar you may not have come across...
Like us, insects have steroid hormones that control a lot of their development - but unlike our androgen and estrogen sex hormones, they have what are known as ecdysteroids. "Ecdy-" comes from "ecdysis", the fancy name for moulting. In fact, there's a taxonomic category that encompasses all animals that undergo ecdysis, Ecdysozoa, which contains arthropods (insects, crabs, spiders, centipedes, etc.), nematodes, and other weird phyla, like Spiderman-like velvet worms and nigh-indestructable tardigrades. All of these organisms use internally produced levels of ecdysteroids to control when they will moult - and also the nature of those moults.
My research organism of choice - the humble fruit fly - goes through three larval stages (each separated by a moult) before turning into a hard pupa while its organs and appendages freak out and switch over to adult-mode. The production of ecdysteroids (and specifically one called 20-hydroxyecdysone) is absolutely necessary for these transitions to take place, as they activate the ecdysone receptor, a protein that switches on the huge number of genes required for such morphological transformations.
So, if these hormones are disrupted, things don't go so well. In fact, genes involved in the synthesis of ecdysteroids have been named, as genes often are, for the problems that occur when they're messed with, and none of them are pretty: spook, phantom, disembodied and shade are just a few of the so-called "Halloween genes". Do dead larvae turn into ghosts?
Enter the Baculoviruses. Scientists love studying these infectious guys for a number of reasons:
- In general, viruses are cool,
- Baculoviruses can be used for the biotechnological expression of proteins in the lab, and
- They're a major nuisance to a lot of agricultural pests.
Harnessing the innate power of already existing organisms to serve our purposes has driven a lot of past research and continues to do so today - and research into using Baculoviruses as pest control agents receives quite a lot of attention. Why develop an environmentally nasty chemical pesticide when you can simply use a virus instead?
Viruses can be nasty, as anyone who knows anything about ebola will tell you, but most of the time they stick to the host they've evolved to torment. Strains of a subsection of Baculoviruses, called nuclearpolyhedrosisviruses (NPVs), are extremely species-specific, and only infect certain moths and butterflies. There's no chance you'll get sick from encountering one, as the virus particles can't replicate themselves within mammalian cells - which is a blessing considering what infections do to moths...
Lymantria dispar, the European gypsy moth, hates its NPV with a passion - or it would if moths could feel hate - because the virus turns it into soup. Infected caterpillars display strange zombie-like symptoms, involving not moulting like they should and instead climbing up trees as high as they can, before they liquify, showering everything below with a rain of infectious used-to-be-caterpillar.
So what the hell is happening? The liquefaction is caused by the extensive reproduction of the virus within the body of the caterpillar, which involves bursting cells to further spread the particles throughout the entire organism. Once enough cells have burst, the caterpillar, as a structure, can't hold itself together and simply melts into goo. This happens with a lot of Baculovirus infections, not just in the case of gypsy moth NPV - but this particular strain is relatively unique in how it uses its soup-making power to its advantage.
For entomological virologists, the zombie-like climbing-of-trees behaviour has been a little harder to explain. They do, however, now know the genetics behind the virus's ability to force the caterpillar to behave in this manner: a single gene called egt.
egt stands for ecdysteroid UDP-glucosyltransferase, which is a bit of a mouthful, I'll be honest. This gene encodes an enzyme that takes an ecdysteroid and connects it to the sugar part of another molecule called UDP-glucose, forming a weird hormone-sugar hybrid molecule. Once the virus is inside the caterpillar, it starts pumping out this enzyme, which attack as much of the non-sugary hormone as they can. This essentially lowers active hormone levels in the caterpillar over time, preventing it from turning into a pupa and allowing it to wander up trees for a soup-splosion.
But why does a hormone with sugar attached no longer do the things a normal hormone would? The answer isn't really about the sugar - well, it is, but the fact that it's sugar isn't really important. What is important is that the active site of the ecdysone receptor, while somewhat flexible, can't handle a bulky molecule like glucose tagging along with the hormone, and the hybrid molecule therefore can't bind and activate the receptor. That glucose is also quite polar (what, with its hydroxyl groups everywhere) doesn't help either.
UDP-glucosyltransferases (and very similar enzymes) are found in uninfected insects as well, where they help mark foreign and potentially harmful molecules for degradation and excretion. This process also occurs in our livers, with glucose or glucose-like molecules being conjugated to a large proportion of the drugs we ingest. This is why painkillers stop working after a few hours or so - your body actively messes with their structure or removes them from the blood through the process of chemical conjugation.
Glucose-conjugation in infected gypsy moth caterpillars, however, becomes out of control, through a gene that the NPV carries and expresses like crazy. It's quite likely that the virus stole the gene from an insect in the ancient past, since viruses, in the end, are little more than parasitic packages of genes and it's quite easy for a new piece of genetic information to slip into the mix here and there.
The whole story with sugar-hormones, nasty viruses and caterpillar soup isn't completely resolved - researchers aren't entirely sure why hormonal inactivation forces the caterpillars to climb higher, but it's a valuable first step to know the viral gene responsible. As someone with a fascination with insect biochemistry, I can't wait to see more papers come out on this topic.
But I won't be having soup for dinner anytime soon.