The curious case of Wipfelkrankheit "disease"

Baculovirus particles

I am sure you have heard of Wipfelkrankheit disease. If you haven't heard of this name at least you must have heard what it's symptoms are. Wipfelkrankheit - or in English, tree-top disease, is a fatal viral infection of caterpillars, an infection that causes them to climb up high, hang upside down and liquify themselves raining down millions upon millions of viral particles to the forest floor below. 

Here they are easily ingested by unsuspecting and uninfected insects. The question of how they do so has been consuming researchers for 100 years. But we may now have the full story. 

The viruses responsible for this are the baculoviruses, a pretty diverse assemblage of large, insect-targeting DNA pathogens. In fact they are so good at killing insects, we now use them remove some of our most unwanted pests. Their genomes contain on average about 100 genes, one of which at least encodes the ability to radically change a caterpillars life. These viruses are perfectly adapted to specifically alter their hosts behaviour to suit their own ends: future replication and survival in an inherently hostile environment. 

These questions largely boil down to asking, how do these tiny viruses cause what is known as enhanced locomotory behaviour (ELA). It's a normal larval behaviour but these viruses somehow force it's dysregulation - either by prematurely activating it or by blocking it's completion. 

Ed Yong (and the guys over at Small Things Considered) actually wrote about this a few months back, where in a Science paper, a group had discovered that for one baculovirus in particular it's egt gene induced the ELA responsible for Wipfelkrankheit disease. If they removed it from the virus, it still infected and killed the caterpillars but it failed to force them to climb vertically higher and higher. They put the gene back in and it restored the symptoms. 

'Melting' gypsy moth

As I said earlier, these viruses are pretty diverse so you can actually split them up into at least two evolutionarily distinct groupings: groups I and II. Both groups have evolved the ability to alter their host's behaviour.  The Pennsylvania State University group looked at how the group II viruses but what about group I? Do you use the same mechanism? Turns out that this evolutionary experiment has run twice and the second time it took a different path. 

Groups I and II of these baculoviruses. Herniou et al 2001

One other group, from Japan this time, has identified the potential mechanism that another gene which controls how  a the group I baculoviruses induces it's caterpillar hosts to display ELA, this time a kind of wandering behaviour in silkworms in response to light. Their discovered protein tyrosine phosphatase (PTP) gene (which they found in 2005) - again when knocked out - failed to induce the kind of Wipfelkrankheit behaviour in their infected insects, however this time they wanted to understand how.

As some of you might have guessed, PTP is an enzyme - a protein molecule that rapidly speeds up certain chemical reactions. In this case, PTP was predicted to remove a phosphate group from particular proteins and RNA molecules. Oddly, this enzyme isn't entirely the viruses, it was actually captured from it's insect host where it carries out it's predicted phosphatase reactions. 

This the group thought was the key to it's Wipfelkrankheit-inducing ability. But when they stopped PTP doing this reaction, miraculously the virus continued to induce wandering/ELA. It turns out that the PTP protein actually acts as a structural component of virus particles and somehow when completely knocked-out controls it's ability to produce functional particles, replicate as good as before and infect caterpillar neural tissues. This fact may lie behind it's ability to alter caterpillar neural activity and incude ELA.

Although the Japanese group did not pursue this theory any further in this paper, they comment:

"We hypothesize that baculovirus infection of caterpillar brain also leads to an excitatory state leading to the induction of the wandering-like ELA that we observe in BmNPV-infected silkworms. "

So it remains a mystery how exactly these viruses achieve their goal of altering their host's behaviour but what this story highlights is the obvious importance of Wipfelkrankheit disease to these viruses. Twice the same phenotype has arisen and both times the viruses have done it differently - just how, we aren't entirely sure. 

Katsuma, S., Koyano, Y., Kang, W., Kokusho, R., Kamita, S., & Shimada, T. (2012). The Baculovirus Uses a Captured Host Phosphatase to Induce Enhanced Locomotory Activity in Host Caterpillars PLoS Pathogens, 8 (4) DOI: 10.1371/journal.ppat.1002644