Creative Commons Xiao et al., Public Library of Science. Click image for link.

I’ve got a new post up at the Scientific American Guest Blog: “Pimp My Virus: Ocean Edition” about the fascinating and newly discovered world of giant viruses. You haven’t seen viruses like this before.  Hope you enjoy!

Dengue virions (virus particles). They are the stack of what look like gumballs getting ready to avalanche at upper right.

Climate change scientists predicted this day would come: Dengue (den-GEE) Fever has re-entered the Florida Keys after an absence of 66 years. The tropical illness, once banished — like malaria– from the deep south, has re-established itself in the Florida Keys, where the CDC estimates that 5% of the population have already been infected.

It is possible the reintroduction has nothing to do with climate change. Certainly increased international travel likely brought us West Nile virus from Eurasia independent of temperature. But warming climates make it easier for the mosquitoes who carry the virus to make a living in more and more northerly climes.

I meant to write about this earlier when I first noticed it in the June 2 issue of New Scientist. But it was a recent article in the New York Times about how locals are shrugging it off that made me take notice.

Though an initial bout with Dengue may seem relatively innocuous, that is deptive. There are four strains of the virus that cause disease, but contracting one doesn’t confer long-term immunity to the others. In fact, it seems to make things worse through a phenomenon delightfully and unusually straight-forwardly named original antigenic sin. If your immune system mounts a response to one form of the virus, it makes antibodies whose blueprints are remembered by special cells called memory B cells. If a slightly different version of the same thing comes along, your body will try to mount a response to it using the cells it’s already manufactured. But because they don’t match well, your immune response ends up being less effective than if it had gotten a chance to tackle the virus with a clean slate.

Scientists hypothesize this may be the reason why people who’ve been infected twice are more likely to develop the more severe form of dengue, dengue hemorrhagic fever. Any time you see the word “hemorrhagic” in a virus’s name, that is not a good sign. It means bleeding — in this case, from leaky capillaries in such places as your gums, mouth, eyes, vagina, gut, skin pores, etc. Doesn’t that sound fun?

And this is not a virus that only attacks the weak. Though mortality rates are low, severe outbreaks have gripped South America in the last few years, including 55,000 reported cases, over 500 cases of Dengue Hemorrhagic Fever and over 60 deaths in Rio de Janeiro in 2008. Did I mention there is no vaccine or cure? Buckle your seatbelts, Southerners.

Aedes aegypti is the mosquito carrier of the Dengue virus. As you can see, the mosquitoes are ready and willing throughout the south. According to the CDC, 2.5 billion people, or 40% of the world’s population, live in areas where there is a risk of dengue transmission. Add the United States to the list.

Dengue viruses are in the Flavivirus family, named for the Yellow Fever Virus (Flavus is Latin for yellow)*. In this family you will also find West Nile virus, Tick-borne Encephalitis virus, and Hepatitis C virus. They’re all rather non-descript little round membrane-bound jobbies about 40-60 nanometers wide. Inside is a polyhedral (a 3-D polygon) protein structure called a nucleocapsid that is 25-30 nm across. Inside that is single-stranded positive-sense RNA (a kind of molecule that contains the information necessary to make proteins) that encodes the virus’s genes. You can get a better sense for how the capsid nestles into the lipid (fatty) membrane in the upper left image here. As with all viruses, the relationship between the Flaviviruses and everyone else is very uncertain, so no tree for you.

One final, adorable note. Apparently, in rural Australia they have trained schoolchildren to depost a “water bug” (in reality a freshwater copepod awesomely called Mesocyclops) that eats mosquito larvae into containers of standing water to help fight transmission of Dengue. Advantages: cost-effective, environmentally friendly. Disadvantage: the copepod is a host for the Guinea worm (remember them?). Good thing Australia doesn’t have Guinea worms.

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*Is it just me or do they need a Flava’Flavivirus family as well?

Punk rockers are clearly dinoflagellate posers. Is it just me or does (a) appear to be a member of the House Harkonnen? Dinoflagellate micro-plankton of Atlantic tropical waters. P. 75. In: "Aus den Tiefen des Weltmeeres" by Carl Chun, 1903. NOAA Photo Library.

Most people have only seen plankton in crappy, fuzzy photos in college textbooks, if they’ve seen it at all. If you have heard of it, it’s probably in the context of the stuff baleen whales eat, and that’s about it. I personally was lucky enough to see an entire jar of the delicacy when I visited the Smithsonian’s Sant Ocean Hall last fall. It looked a lot like the larvae of the neural parasites that took over the brains of the Federation’s top brass in the first season of Star Trek: TNG. Mmmm, mmmm good!

Plankton is not a taxonomic/phylogenetic group like most of the things I write about on this blog. Plankton instead refers to any sea creatures that drift. That can include things as large as jellyfish, but typically plankton are much smaller and include things as small as the bacteria, archaea, and viruses with which the oceans teem. The phytoplankton, or photosynthesizing component, are responsible for half of the oxygen you breathe.

Well, someone’s finally taken some skillful, beautiful pictures of the plankton and they’ve gone on display at the London Zoo in honor of the Royal Society’s 350th Anniversary (Dang! That Society’s been around over 100 years longer than my country!). Over at the BBC there is a don’t-miss slide show of the exhibit, narrated by the scientist photographer, Dr. Richard Kirby. Let me repeat that: DON’T MISS THIS SLIDE SHOW.

You’ll get to see how evolution has taken body plans on some interesting trips, as larvae that retain ancestral forms metamorphose into sea creatures you are more likely to recognize. The squid-like larval origin of starfish, in particular, is a fascinating thing.

One final note — Dr. Kirby mentions that plankton are responsible for the characteristic smell of the sea. That is not surprising to me. When I was a grad student in plant pathology at Cornell, I was startled one day to discover that dirt doesn’t smell like dirt. Dirt smells like the bacteria that are living in dirt. In one lab we were allowed to sniff (I believe “waft” is the preferred term) a pure culture of soil bacteria. It was a clear agar dish with opaque colonies of bacteria. But it smelled just like fresh topsoil or a cave — dirty, earthy, wonderful.

Discovered thanks to the fine staff of Deep Sea News.

Rinderpest is somewhere in this image, but the source did not describe where. If I had to guess, I'd say it's the rods and that they're packed into a host cell with a few floating free. If so, the rods also have a membrane around them that is difficult to see. Copyright held by Dr. Rajnish Kaushik, Creative Commons Attribution-ShareAlike 2.5 License.

Extinction has a flip side: eradication. We did it to smallpox (or rather, almost did it; a few samples survive in U.S. and Russian labs), and though the ethics of that are interesting to think about as an intellectual exercise, there is no question that it has relieved the suffering of millions. Scientists are on the verge of doing it again with two organisms: another virus and an infamous parasitic worm. The obliteration of either one would mark only the second time this has happened in human history, and the first in 30 years.

Rinderpest is a vicious livestock virus that has sickened hundreds of millions of cattle in Eurasia and Africa since ancient times. In herds that have never encountered the disease, it can fell nearly every animal, and it’s not a pretty death: weeping mouth and urogenital ulcers, constipation followed by diarrhea, and a struggle to breathe. Though the virus affects only cattle and related wild animals like wildebeest and giraffes, when millions of cattle die, their keepers starve.

The rinderpest virus, a paramyxovirus in the “genus” Morbillivirus, seems to be related to the measles, mumps, and canine distemper viruses. Rinderpest is an RNA virus, which means it uses the material we normally use to translate DNA into proteins as its hereditary material. For the bio geeks out there, it’s a negative-sense virus, which means the genome has to be translated into the positive sense by an RNA polymerase conveniently packed into the virion. The positive sense strand then acts as mRNA and can make all the virus’s hijacking, lockpicking, and get-out-of-cell-free proteins. When the virus is done replicating, new negative-sense RNA and a sampler of the appropriate proteins are then enveloped by a membrane spiked with fusion and attachment proteins that help the virus get into cells.

Every paramyxovirus has  but a single strand of RNA, on which a mere 6-10 genes lie. In Morbilliviruses, there are exactly three nucleotides (A(denine)s, G(uanine)s, C(ytosine)s, or U(racil)s) between each gene, which is incredibly efficient packaging for those of us familiar with the thousands and millions of non-coding nucleotide bases between genes in be-celled life. The order of the genes is conserved too because the virus practices “transcriptional polarity”, a phenomenon in which genes closest to the “beginning” of the RNA strand are transcribed more often than the ones at the end. That’s probably because the protein that translates the strand — the RNA polymerase — has a tendency to fall off before it’s finished. This provides cheap and easy transcription regulation, but also a strong incentive not to shuffle your genes. What I’ve told you so far applies to Morbilliviruses and Paramyxoviruses in general, but other than its mug shot, above, I can’t find out much more online about Rinderpest’s particular modus operandi.

Strangely, in spite of its prowess, the virus never succeeded in reaching the Americas. And in spite of a reliable vaccine and the near elimination of the virus from Africa in the 1970s, we didn’t finish the job, and tens of millions of livestock were dying again in the early 1980s. Finally, in 1993 the UN Food and Agriculture Organization had enough and decided it was time to bring it to the virus. 17 years later, the end game is at hand. You can read more about the history of the virus and eradication effort and how close we are here (subscription required) and here to only the second intentional extinction on Earth.

Next time: Reason # 1,356 to be thankful for your local water treatment plant: Guinea Worm.

Sitting in the spice rack of many an Asian home, and a very few American homes, is the unusual looking fruit of an ordinary-looking plant with an unexpected use. Here is that plant:

Delicious or deadly? Both -- depending on your perspective. Image by Shu Suehiro, licensed under the Creative Commons Attribution 3.0 Unported License. Click for link.

And here is its fruit:

Science? Art? My favorite intersection. The shiny objects are the seeds. Image by Bryan Arthur, distributed under the under the Creative Commons Attribution ShareAlike 3.0 License. Click image for link.

The plant is star anise, Illicium verum.

If you know it at all, it is as a spice. As its name implies, its flavor is licorice-y, and indeed the plant makes the same flavoring chemical found in true anise, fennel, and licorice: anethole. It can be used on its own in Asian cooking, but is more commonly known for its inclusion in Chinese five spice powder and Japanese seven spice powder. If you’ve never tried one of these blends, do yourself a favor take some for a spin.*

And now for the use you probably didn’t know about: star anise is the raw ingredient used to make oseltamivir, more familiarly known as Tamiflu. The actual raw ingredient is shikimic acid, and many plants, including the North American Sweetgum (with the beautiful genus name Liquidambar) also make it. But star anise is particularly good at making it. The yields are high.

It seems odd to think of a modern drug depending on a botanical source, but tamiflu is seemingly still very much in that category. In 2005, shortages in Chinese star anise production caused a shortage of Tamiflu.

Nonetheless, it takes some fairly heavy organic chemistry gymnastics to get from shikimic acid to oseltamivir. The wikipedia entry notes, in rather understated language,

Some of the steps in the synthesis require careful handling and relatively mild reaction conditions, as they involve the use of potentially explosive azide chemistry.

Hooo-kay. Having taken organic chemistry, I really do believe that organic chemists earn every penny of their six-figure incomes. You’ll also easily realize, if you compare the structures of shikimic acid and oseltamivir, that the Chinese health minister’s suggestion that people in China cook their pork with star anise to ward off influenza is absolute rubbish. They look totally different. And if it takes a 10-step process involving “potentially explosive azide chemistry” to get to oseltamivir from shikemic acid, it ain’t gonna happen in my stomach. Nor can you get swine flu from pork (duh). Still, pork + star anise could well = tasty.

Star anise’s price still rises and falls with flu outbreaks, even though 99.6% of last year’s seasonal flu was resistant to Tamiflu (a sobering and staggering rise from only 12% the year before) and the same thing could easily happen to pandemic H1N1 flu. Still, so far only 39 of 10,000 pandemic H1N1 flu samples tested positive for resistance to Tamiflu in October. And doctors still turn to Tamiflu to fight this flu. Just a few weeks ago, the U.S. Government decided to release the last of its children’s Tamiflu stockpile due to this flu’s disproportionate ability to kill the young — even, disturbingly, some who were apparently otherwise completely healthy prior to infection.

But it’s hard to believe with hundreds of thousands of doses of Tamiflu flowing into all regions of the U.S. that the drug will last long against the virus. Between this and newly developing E. coli-based shikimic acid production techniques, star anise’s run as a flu-fighter will probably be short lived.

Next time: The Curious Taxonomy of Star Anise

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*Chefs are cooking with five-spice powder more and more as they experiment with traditional ingredients in new cuisines. I often make crispy tofu-ginger fritters with five-spice powder, and I also recently found a recipe in Cooking Light for pumpkin pie with five-spice powder. I bet it’d also be good as a replacement for cinammon in snickerdoodles, since cinnamon is one of the ingredients (in my commercial “Asian Gourmet” blend they are, “cinnamon, anise, fennel, ginger, clove, and licorice root”. I note with amusement that makes six.)

Apparently, in addition to all things jelly, I’m fascinated by all things blobby. You’ll note the restraint I used in not posting anything about that blob they found floating off the coast of Alaska last summer. It seemed obvious right from the start that that was simply your run-of-the mill algal bloom. These blobs, on the other hand, would quite mystify me without  the help of a reassuring National Geographic narrator.

I’m pretty sure this is the same stuff that builds up in the water you leave the dishes in the sink too long. Is it just me or did you also half-expect to see an eyeball or two floating around in one of those things?

It seems like this may be some sort of biofilm, which is a very sexy subject in the world of biology right now. Biofilms are essentially thin coats of bacteria and bacterial slime (technically known as extracellular polymeric substance, or EPS) on teeth, stream cobbles, catheters, lawyers, etc. (just kidding lawyers! Don’t sue!)  These things are apparently everywhere — even on the thin skin of water at the surface of the ocean — and this way of life represents an up-till-now severely underappreciated bacterial lifestyle. 99 percent of bacteria may live in biofilms.

And yet  these don’t seem like classic biofilms as they aren’t tightly packed or adhered to a surface. They seem to be somewhere in the no-man’s-land between a biofilm and marine snow, the slow rain of decaying microbial matter that eventually coats the ocean floor. Both marine snow and mucilages incorporate much more than just bacteria — like crustaceans, plankton and viruses. For whatever reason the marine snow in the northeastern Mediterranean is piling up faster than the life in the water column or on the sea floor can take it out. Which seems odd, because in the deep sea, the locals will quickly consume anything that isn’t ballistic-grade plastic, and I’m pretty sure they have their R&D departments working on that too.

Whatever they are, they are unusual, and probably prospering by climate change. I love weird manifestations of life, but there is good-weird and there is bad-weird. The kind of weird that smothers fish and spreads E. coli is definitely bad-weird.

For the PLoS paper that inspired this video, click here.

A membrane, some proteins, and 8 segments of RNA: all there is to influenza. A false color transmission electrion micrograph of the influenza virus. Image courtesy CDC/ Erskine. L. Palmer, Ph.D.; M. L. Martin

Until 1933, it was impossible to see a virus. Oh, we knew they were out there. But no one had the faintest clue what they looked like. 1933 marked the year transmission electron microscopy finally achieved resolutions finer than light microscopes were capable of and made it possible to finally glimpse the agents that had mottled tobacco leaves, streaked tulip petals, scarred the faces and bodies of millions, or paralyzed, maimed, and killed millions more.

So what’s with the doofy colors? Yes, in spite of the awesomely awesome resolution that transmission and scanning electron microscopes provide us with, scientists and alarmist pandemic book cover designers can’t seem to resist painting them with gaudy colors (see above). OK, I admit the colors do seem to spice up the images. But this isn’t even a case of colorizing something that was colorful to start with — viruses are quite clear. So what a revelation to see a glass artist team with scientists to produce anatomically correct transparent glass sculptures of viruses and other wee animalcules. That’s exactly what British artist Luke Jerram has done, and his creations are truly illuminating.

It's hard to believe, but cashews actually *do* grow on trees. A glass model of Anacardium occidentale, the cashew tree, on display in the Harvard Glass Flower Collection. Model by Leopold and Rudolf Blaschka.

I must say that his models remind me very much of the intricate glass 19th century models of fungi, invertebrates, and plants I discovered in my college days in dusty corners of Cornell and Harvard, many of which were created by the father and son team of Leopold and Rudolf Blaschka in Dresden, Germany from the 1880s to 1930s. They definitely get my vote for having the C00Lest Jobs EVAR. Intended as teaching aids, they date from a time when color photographs were unheard of and microscopes were a bit primitive. The colored glass models were able to show fine detail far better than either an engraved image or tiny eyepiece could, they did so in 3D, and as the Harvard people like to point out, glass flowers bloom year round. It’s nice to see that everything old is new again.

Viral family trees

The filaments of the Marburg virus, which can be straight or contain a "shepherd's crook", and which gave the filovirus family its name.This photo of the Marburg virus brought to you by the number 11, the letter d, a backwards Egyptian s, and an important (and suggestive) year in US history with a bubble wand on top. Also, by the CDC and Drs. Erskine Palmer, Russell Regnery, and Hermann Rorschach, who in no way support or endorse my interpretation. Magnification 100,000 x.

As if the bats of the world didn’t already have enough to contend with, what with their bad (albeit sometimes deserved) rap for rabies and drinking human blood, numerical decline thanks to habitat loss, and the White Nose Syndrome that is anihilating the bats of eastern North America (and maybe eventually all of North America), last month came news that a reservoir for the deadly Marburg virus had been confirmed: African cave-dwelling fruit bats.

This is big news because scientists have been looking for the natural reservoir species for Marburg and its cousin Ebola for some time. Marburg and Ebola are hemorrhagic fever viruses that are among the deadliest on the planet*. They are sole members of the Filovirus family, and are single-stranded negative-sense RNA viruses. Mortality rates range between a quarter and nine-tenths of those infected. And Marburg is not a pleasant way to go. Here’s how the CDC describes it:

After an incubation period of 5-10 days, the onset of the disease is sudden and is marked by fever, chills, headache, and myalgia. Around the fifth day after the onset of symptoms, a maculopapular rash, most prominent on the trunk (chest, back, stomach), may occur. Nausea, vomiting, chest pain, a sore throat, abdominal pain, and diarrhea then may appear. Symptoms become increasingly severe and may include jaundice, inflammation of the pancreas, severe weight loss, delirium, shock, liver failure, and multi-organ dysfunction.

Sounds fun! Hemorrhagic fevers are so called because they somehow punch holes in capillary walls that allow blood to seep into the body and out of certain external openings you would not wish blood to ever pass through. As recounted in Richard Preston’s gruesome early 90’s bestseller  The Hot Zone , this can cause people to spill or spatter infectious blood all over any unfortunate passersby or airline seatmates (sometimes the little “summon stewardess” button can’t fully convey the depth of your need). It must be said, however, that the bleeding isn’t usually what kills you, and that unlike its cousin Ebola, Marburg is not nearly so inclined to make you bleed from bodily orifices. Whew!

In The Hot Zone, Preston described (at least in my memory) how some cases of Marburg or Ebola were found in people who recently visited mines or caves or who had spent times in rooms or factories where bats roosted. Although some people seemed to acquire the virus from sick apes or bushmeat, scientists already suspected the virus reservoir, or full-time host, was not apes or monkeys, because they die just as we do from the virus. Suspiciously, however, apes and monkeys that transmitted the virus had often fed at fruit trees that bats frequented. But repeated tests of bats and the sticking of unfortunate “sentinel species” in caves to see if they got sick could never produce leads. For decades, scientists were baffled and frustrated. How could such a deadly virus remain so mysteriously hidden?

Then four years ago a survey of more than a thousand small vertebrates Gabon and Democratic Republic of Congo during an Ebola outbreak turned up evidence of asymptomatic Ebola infection in bats, hinting they might be the long-sought reservoir. Inspired, scientists in 2007 finally isolated antibodies and Marburg virus genetic fragments from fruit bats. Then last month an article in PLoS Pathogens contained the damning evidence: the isolation of live infectious viruses from the Egyptian fruit bat (Rousettus aegyptiacus) in Kitaka Cave, Uganda. There can be little doubt now that bats are carriers.

Could you resist this face? No! Bad bat! Don't give me deadly Marburg Hemorrhagic Fever! The Egyptian Fruit Bat, Rousettus aegpitiacus. Courtesy Dawson, Creative Commons Attribution 2.5 License.

The infected bats appeared healthy, and the genetic diversity of the viruses found in Kitaka Cave seems to indicate Marburg has been living with and adapting to the bats for a long time. If the virus had only recently penetrated the bat population from another species, you’d expect there to be only one or a few virus types.

Moreover, a significant share of the bats in the surveyed cave are infected. About 5.1% of their sample hosted the virus, which, if extrapolated, would mean over 5,000 bats out of an estimated 100,000 in the cave are infected. And indeed, two miners infected in Kitaka were sickened by different strains of the virus, implying they picked up their diseases independently and that human transmission is not a rare event. The strains, though different, closely matched the sorts of strains found in the scientists’ fruit bat samples.

Although the viral lineages were highly variable within Kitaka Cave, some strains found in one part of Africa were much more closely related to strains found in caves hundreds of miles away than they were to strains in their bat neighbors. As the bats migrate hundreds of miles and mingle over most of the continent annually, it’s not hard to see why Africa may be one giant Marburg virus melting pot.

I just hope this news doesn’t prompt a bat holocaust in Africa on the part of people, corporations, or authorities. Bats have enough troubles already and [cliche alert] provide valuable ecosystem services[/cliche alert] by hoovering up pesky insects and/or dispersing seeds. The solution, I think, is bat avoidance, though how practical that is in a mine I do not know.

Note to self: scratch caving in Africa off to-do list**.

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*In other news, the first-ever case of Marburg in the United States was recorded in February in Colorado . . . wait, what? A deadly Ebola relative made its way to Colorado this year and I didn’t even know it? How they managed to keep the fact that a virus with a 90% mortality rate was in Colorado on the DL I’ll never know, although I did find an article in the Rocky (RIP) about it ex post facto. I need to start keeping closer tabs on our local newsgathering establishment.

**Several of the people who got sick (including the Colorado victim) did so after visiting some sort of “python cave” in Uganda that also is home to thousands of bats (do the snakes just sit on the ground with their mouths open waiting for manna from heaven?). Second note to self: question sanity if *ever* consider visiting something called a “python cave”.

“Snakes. . . . why’d it have to be snakes?”

“Pythons. Very dangerous. You go first.”

Kind of eerie and ghostly, isn’t it?

It’s a virus that infects bacteria, looks like the lunar lander, and was among the first viruses ever discovered. These guys may also be the most ubiquitous biological entities on the planet; you may be swallowing untold millions in every accidental mouthful of fresh or seawater. Did I mention the water’s teeming with the bacteria and archaea they prey on too?

Most viruses are either simple rods, spheres, or polyhedrons (often icosahedrons — 20-sided polyhedra, of course). This baby is both and then some. In the world of virus architecture, this is the fully loaded Corvette with T-tops, all-leather seats, and pre-installed hot chick. It is a natural work of art.

So why didn’t someone think of this sooner?

I have no idea who this guy is but I like how he thinks. There’s a certain delicious irony in using old computers to build models of . . . viruses. My capsid’s off to you, sir. Who needs a lawn gnome when you can have a lawn phage?