How a zombie virus became a big biotech business

By Carl Zimmer | May 23, 2011 3:42 pm

Sometimes a blog must serve as a repository of regrets, a place to atone for not including some perfect fact in a book. While working on my book Parasite Rex, I came across many delicious examples of parasites manipulating the behavior of their hosts for their own benefit. After the book came out, I met scientists who enlightened me about other examples which would have been wonderful to include. A few years back,  for example, a Johns Hopkins scientist pointed me to a parasitic wasp that turns cockroaches into zombies.

I’ve recently been wondering about behavior-altering viruses, thanks to an online conversation I had with Ian Lipkin, a virus hunter at Columbia University, about my new book A Planet of Viruses. Lipkin wondered aloud if some viruses would turn out to manipulate their hosts for their own good. Did herpesviruses, for example, increase its transmission by boosting their host’s sexual desire?

Most of the examples I knew about came from parasitic animals and fungi. The only virus that could have this kind of effect that I knew of was rabies, which causes its hosts to become more aggressive. A rabid dog that bites anything that crosses its path may be able to spread the virus more. But I suspected that there were many other puppet master viruses out there.

Well, while I was at California State University Fresno last week to give a talk, I met an entomologist named Fred Schreiber. He asked me if I had ever heard of baculoviruses. They rang a bell in my head, but only faintly. So Schreiber told me an eldritch tale…

Baculoviruses infect invertebrates, with each species of virus typically infecting only one species of host. Caterpillars are a particularly favorite target; the insects swallow baculoviruses sprinkled on the leaves they munch. (“How did the viruses get there?” you may ask. Very good question–which we’ll get to in good time.)

Once inside the caterpillar, a baculovirus infects a host cell. The cell produces huge numbers of new baculoviruses. They come in two forms. Some of the viruses can slip out of the host cell on their own to infect new cells. Others stay in the cell, which makes huge quantities of a viral protein called polyhedrin. The viruses become embedded in massive polyhedrin blocks,  like fruits in a fruitcake. A caterpillar may produce 10 million viruses from swallowing a single viral fruitcake. It even becomes visibly swollen with all its new viruses.

Soon the virus-packed host gets an uncontrollable urge to creep its way to the tops of plants, where it clamps on tight, hanging down as shown in the picture above. In fact, scientists noticed these strange death throes long before they knew that baculoviruses that caused it. They dubbed it tree-top disease.

After an infected caterpillar takes its position at the top of a plant, the virus releases an enzyme that literally makes the animal dissolve. The tough viral fruitcakes come tumbling out, landing on leaves below where they can infect a new host.

Hearing about tree-top disease gave me a deep sense of deja vu. A number of very different parasites have evolved the same strategy for getting to new hosts. Just a couple weeks ago, for example, I blogged about a fungus that sends its ant hosts to the undersides of leaves, whereupon the fungus sprouts branches out of the ant’s head and showers spores down on new victims. Lancet flukes send their hosts up to the tips of grass blades so that they can be eaten by grazing cows and sheep. It’s fascinating that even a virus–with just a few genes–can trigger this behavior as well.

Scientists have identified one of the genes in baculoviruses that is crucial for this manipulation. It causes insect hosts to start wandering in response to light. Strangely, the virus appears to have acquired this gene through a kind of evolutionary theft. The viral gene bears a striking resemblance to a gene in insects. In the insects, the gene is involved inforaging for food. It’s possible that an ancestral baculovirus picked up the host gene, which then evolved to take on a different behavior–one that sent insects to their doom, rather than to a meal.

All in all, this zombie strategy is terrifically successful for baculoviruses. They are everywhere, killing insects in staggering numbers. In 1973, scientists bought heads of cabbage around Washington DC and discovered that they were coated in baculoviruses. A single serving of cabbage contained up to 100 million of them.

Fortunately, baculoviruses are so finely adapted to invertebrate hosts that they pose no threat to humans. In fact, we can use baculoviruses to our advantage. Scientists can remove the polyhedrin gene from the viruses and replace it with another gene of their choice. If they infect an insect cell with the engineered virus, it will make dense blocks of the protein they desire. Thanks to the sophisticated biochemistry that baculoviruses use, they allow scientists to harvest high concentrations of the protein. As a result, baculoviruses have become a mainstay of the biotech industry, where they are engineered to make vaccines and other drugs.

Baculoviruses are also popular as a way to control pests in farm fields, and for years, scientists have been trying to engineer the viruses to become even nastier to their hosts. Ironically, this manipulation of the virus may get in the way of the virus’s own manipulation of insects. Scientists have found that engineered viruses end up paralyzing the caterpillars before they can get a good grip at the top of plants. They fall to the ground, and so they can’t showering more victims with the virus.

We shouldn’t be too disappointed at this sort of failure. After all, evolution has been fine-tuning these viruses for millions of years. Our imaginations may need a little more time to improve on the elegant horror that lurks in your salad.

[Image: Bill Tyne/Flickr]


Comments (14)

  1. Another fantastic find. The fact that the virus makes the host -dissolve-? That’s crazy-talk. Sounds like there is a good fiction novel in this, somewhere …

  2. Fantastic story – and I’m glad to have played a small part in bringing you to Fresno so you could hear of this from Fred!

  3. I love this post! May I write about this in my blog, if I give the link to this site and refer to your work? It is still new so I have not pinpointed my themes yet but my longing is to write about science as if it was spiritual (cause it is to me), to confer a sense of wonder that we are alive here on this fantastic planet. Perhaps I should emphasize that I am not into intelligent design or creationism, on the contrary.
    I would like to write about how we have become virus-farmers in order to decrease the use of pesticides and refer to your text, I will not copy it but I would like to use the image of the catepillar if that is ok? Perhaps you are using it with kind permission from another person. Otherwise I can google for more.

    Best wishes

    [CZ: Anna, you can go to the Flickr page for the image and use the image under the Creative Commons license described there.]

  4. Politicians. Corporations.

  5. hexatron

    Making a caterpillar dissolve is probably a pretty simple genetic trick. Caterpillars dissolve themselves in the normal course of turning into butterflies.

  6. Daniel J. Andrews

    I finished your new virus book and my only complaint is that it is far too short and doesn’t delve indepth into so many of the fascinating stories and people that must lie behind the discoveries. I can imagine you’d easily be able to triple the size of the book even if you didn’t include all the new things being discovered (which I hope you do anyway so quadruple the size of the book). If you decide to do an indepth look at the viruses and the people doing the research, I’d buy that one too.

  7. God, that’s amazing! I’m kicking myself for not having heard about this either — but it makes me feel better that you hadn’t heard about it, since “Parasite Rex” was where I started my research into parasitology.

    Some of the details in there are wonderful. A viral infection that makes its host bloat up from the shear load of viruses inside? That’s amazing. The enzyme dissolving the host’s body reminds me a little of the ant-decapitating fly larvae dissolving the membrane that hold its host’s head on, but that’s mostly just free-association.

    Thank you for posting about this!

    – Brandon

  8. Bill Tyne

    The current research on baculoviral chitinase (one of the two enzymes involved in liquefaction of the host, the other being cathepsin) is inconclusive with regards to its origins. While early studies focussed on the similarity of baculovirual chitinase to the chitinase of the bacteria S. marsecens the use of phylogenetic analysis has proved inconclusive. The enzyme is not, however related to the eukaryotic chitinase found in the insect host. There is a very similar version of chitinase found in some lepidoptera that is usually abbreviated chi-h. Chi-h appears to be prokaryotic in nature (no intronic sequence just promoter and a single reading frame).
    The paralysis induced by some engineered viruses was a deliberate modification to prevent the host from continuing to feed during the period post infection until it died (the gene for scorpion toxin was introduced into the viral genome). The reson for this was simply that the virus took a period of days to kill the host, during which time it would continue to damage crops unless immobilised. The research into scorptox ceased due to adverse publicity, this being around the height of the GM scare stories that were prevelant across the UK.

  9. Seems like they have discovered a real zombie virus that infects humans. The first confirmed case is the cannibal in miami. Would this be a billion dollar industry as well?


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The Loom

A blog about life, past and future. Written by DISCOVER contributing editor and columnist Carl Zimmer.

About Carl Zimmer

Carl Zimmer writes about science regularly for The New York Times and magazines such as DISCOVER, which also hosts his blog, The LoomHe is the author of 12 books, the most recent of which is Science Ink: Tattoos of the Science Obsessed.


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