Visualizing the virus

Posted: Wednesday, April 29, 2009 6:15 PM by Alan Boyle

NIAMS

Surface proteins stick out in this
3-D image of a flu virus.

How can one bug combine genetic material from pigs, birds and humans to become so dangerous? Think of flu viruses as promiscuous, species-jumping, disguise-wearing contestants in a reality-TV show titled "Evolution Gone Wild." Virus-fighters are scrambling to keep pace, using analytical techniques that work more quickly than ever.

This show is no comedy, as illustrated by today's news about the first U.S. death in the swine-flu epidemic and the escalation of the World Health Organization's pandemic alert status. But knowing how the virus game is played could help you understand issues ranging from the difference between vaccines and antivirals to the reasons why you can't get the flu from a pork chop.

Viruses are outfitted to pry their way into your cells, hijack the protein-making machinery inside, then break their way out and proliferate. The key package is the set of RNA molecules lurking inside the virus' shell. Those single-helix RNA molecules contain the instructions for assembling a cell's proteins into more viruses.

Flu viruses are so hard to get a handle on because they can swap bits of RNA inside the cell, creating a fresh genetic patchwork that emerges as a new virus strain. The fact that the flu virus depends on RNA rather than DNA increases the likelihood of mutation, because the RNA doesn't even try to correct the errors that crop up during replication. It just lets the evolutionary chips fall where they may.

Your immune system can create antibodies that lock onto a virus and keep it from breaking into your cells. But the antibodies won't immediately come to the rescue if the virus has disguised itself through genetic recombination.

That's where vaccines enter the picture: They can sensitize your immune system to recognize the virus in a new disguise. The first step in making a vaccine is to see through that disguise. And fortunately, the quickening pace of genetic analysis is streamlining that part of the process, making it possible to track down a flu virus' identity in hours rather than days or weeks.

The rapid response paid off when it came to identifying the virus behind this month's flu outbreak. "The first specimens took roughly six hours from when the box was opened," David Daigle, a spokesman for the federal Centers for Disease Control and Prevention, told me via e-mail today.

The CDC's lab had its sequencers primed and ready to go in advance - first to identify the virus as a swine-flu strain, then to get a complete genetic sequence. "Looking at that genetic sequencing data, you can draw conclusions about the origins of this virus," said John Treanor, a virus expert at the University of Rochester.

The virus was classified as an H1N1 type - the same general type that was seen during the 1976 swine-flu outbreak, but with some novel twists. CDC official Nancy Cox said the virus' RNA mixed together bits from North American avian flu and swine flu, at least one bit from human flu, and at least two bits from Asian and European swine flu.

How did all those bits get mixed together? Pigs are regarded as particularly good "mixing vessels" for RNA swaps, because they can contract flu viruses from humans and birds as well as other swine. All those bits of RNA can recombine within the pigs' cells, resulting in lots of possible disguises for the resulting viruses. One of those genetic disguises was so successful that the virus made another species-crossing jump from pigs to humans.

Now that the virus' genetic sequence has been decoded, it can be used as a fingerprint to track its spread. "For the first time in history, we can track the evolution of a pandemic in real time," WHO Director-General Margaret Chan said at a news conference today.

Just as a refresher, here are some other scientific flu facts:

Flu infections are a fact of life for pigs, but swine flu is rarely passed along directly to humans: It takes just the right genetic twist for the virus to make the jump between species. Swine-flu virus is not passed through food. "Eating properly handled and cooked pork and pork products is safe. Cooking pork to an internal temperature of 160 degrees F kills the swine flu virus as it does other bacteria and viruses," the CDC says in its swine-flu briefing. The concern about swine-to-human transmission has more to do with being in contact with live pigs.
Vaccines train your immune system to block the molecular machinery that viruses use to break their way into your cells (a.k.a. hemagglutinin, the "H" in H1N1). Those vaccines are not designed to stop an infection once it's started. In contrast, antiviral drugs target the machinery that viruses use to break out of your cells (a.k.a. neuraminidase, the "N" in H1N1). Those drugs stop the virus' life cycle in its tracks. The current manifestation of swine flu can be stopped by the antivirals Tamiflu and Relenza (but not by amantadine or rimantadine).
As a flu virus spreads, the chances of further mutation become greater, experts say. And that means there's a chance that a deadlier virus could emerge. That's why it's particularly important to limit the spread of this latest swine-flu virus. But viruses aren't all bad: In fact, evolutionary biologists have seen signs that viruses can give some species new genetic capabilities - and viruses have been used intentionally to help humans.

Finally, here's a list of resources that delve into the science of flu viruses - including some great visualizations showing how the viruses do their thing:

Update for 8:15 p.m. ET: The Loom's Carl Zimmer links to a quick and easy survey on attitudes toward the current swine-flu outbreak. Be a part of the scientific process and take the survey.

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Comments

One interesting tidbit of information is the ability of the body to respond to an infection such as the swine flu. It may be our antigenic response that is the killing agent in the swine flu. The body removes proteins that carry a specific signature. If the flue virus carries a protein or genetic constituent that is very similar to proteins in our bodies, then our bodies remove healthy as well as infected tissue. Lung function drops dramatically as they fill with fluid. Genomic analysis of increased host immune and cell death responses induced by 1918 influenza virus
Nature doi:10.1038/nature05181 This would also suggest that mortality from the swine flu will be dependent on the hosts (sick persons) immune response; thus, an explanation for the strange demographics of swine flu.

Steven Albee-Scott, Logan, UT (Sent Wednesday, April 29, 2009 9:45 PM)

as for controlling this mexican flu, reports are suggesting that the new drug `tamiflu` is effective in controlling this illness. quite remarkable really that this broad range flu control drug developed incase another similar epidemic as the recent oriental bird flu outbreak a couple of years ago broke out. seems very quick work to make a flu vaccine that works for this flu, considering that the developers of tamiflu did not know the structure or genetics of this new `mutated` bird , swine and human flu seen in mexico, it is a wonder at all that it works. it took 10 years of development to make a partly succcessful AIDs drug and so far the drug companies have been trying unsuccessfully to make a flu and cold vaccine drug for years and years, such information suggests to me that it is against all odds that tamiflu works after such short development, especially against the H1N1 type that this is ??

iain newby (Sent Thursday, April 30, 2009 3:46 AM)

The world's farmers have a stone age mentality in an urban world. They have to learn that their failure to learn how to clean up their manure is endangering the life of every person on this planet.

George Costich (Sent Thursday, April 30, 2009 6:32 AM)

Alan, while I truly love your column, I think that the second paragraph should instead read "This show is no comedy, as illustrated by the deaths which have already occurred in the swine-flu epidemic and the escalation of the World Health Organization's pandemic alert status." I'm sure none of the families who have lost loved ones in Mexico would consider it to be a comedy either.

Michael, Columbus, Ohio (Sent Thursday, April 30, 2009 8:14 AM)

Can we imagine an STD being transmitted to an animal whoes RNA is a breeding ground for genetic mutations. The result could be an airborn STD and you think HIV was bad H6N9 may be a way of life or maybe a great movie.

Dave Ithaca NY (Sent Thursday, April 30, 2009 8:45 AM)

The idea that multiple viruses can come together to make a new virus, doesn't seem too scientific to me. It sounds a lot like sexual reproduction. I'm no biologist, but I've never heard of such a thing amongst viri.

I am going to need to see some documentaton before I believe this is possible. Preferably, a real microscopic picture of a real set of viruses, really behaving as described.

Until then, I have to dismiss this as "Theory".

Joseph

Joseph Frazier, New York, NY (Sent Thursday, April 30, 2009 9:11 AM)

Finally, a factual and well written article about a very complex virus, with serious pandemic capabilities. More of these articles should be written and posted, so that the general public can make sound decisions based on fact rather than hysterical hyperbole. Thank you Mr. Boyle.

MS, San Diego, Calif (Sent Thursday, April 30, 2009 9:41 AM)

If one were doing a bit of guessing based on a combination of education, intuition, and mentation, one might suggest that the cause of this particular blend of avian, human, and porcine influenza ultimately will be traced to a combination (a) of outrageously unregulated corporate mega-farming and (b) of feeding pigs a completely and totally disgusting blend of "by-products" from all three of the major genetic contributors (avian, human, porcine), as well as a lot of other stuff that pigs never should be fed . . .

Stated another way, this new so-called "swine flu" is little more than yet another consequence of allowing sneaky weasels to violate virtual festivals of the Basic Rules of Nature, where for example one of the rules is that bovines are not supposed be fed "by-products" derived from the carcasses of bovines or any other types of animal "by-products", because first and foremost bovines are herbivores . . .

Another example is that it is not a very bright idea to use raw or processed human sewage as "fertilizer" for all the happy fruits and vegetables which sooner or later are destined to appear in the food baskets from which otherwise reasonably bright humans obtain their sustenance . . .

And while pigs, hogs, and swine are omnivores, a bit of common sense tends to be useful when determining the best types of livestock feed . . .

One might suggest that the best rule is that, "It is not nice to fool Mother Nature!", by for example, inserting human genetic sequences into pigs, sweet potatoes, and no telling what else, even when according to the sneaky weasels such Frankenexperiments produce results that "appear" to be just like normal stuff . . .

And although one might expect that Mexico generally being the so-called "cradle of corn" would make it unlikely that Mexican pigs, hogs, and swine were fed Frankencorn, a bit of focused investigating reveals otherwise, especially since Mexico-based Seminis, once the largest seed company in the world, was acquired several years ago by Monsanto, the undisputed leader in Frankenseed, polychlorinated biphenyls, highly toxic herbicides (including Roundup, its flagship brand), aspartame, and recombinant bovine growth hormone (rBGH). . .

All this nonsense started over a century ago and slowly but surely as increased to the point that it is virtually worldwide, and in part it is based on a patently evil agenda which is not so difficult to understand when you take the time to ponder it for a while . . .

The short version is that if it did not exist on this planet 2,000 years ago, then it probably does not belong on your table in a plate when it is time to enjoy a healthy meal . . .

For example, starting sometime in the 1920s when oleomargarine first was introduced, along with packs of yellow dye so that cooks could make it look more like butter, the sneaky weasels embarked on a grand effort to convince otherwise bright people that butter was "bad". The sneaky weasels have been very successful in doing this over the years, primarily by paying other sneaky weasels to do "research" which focuses only on very specific components of butter rather than on the Gestalt, since when one focuses on the Gestalt one soon discovers that butter has other components which balance the so-called "bad" components . . .

And the same thing started happening in the early 1980s with the large-scale introduction of the strange and bizarre Frankensweetener named "high-fructose corn syrup", which did not exist on this planet until it first was concocted in a research laboratory in the US in the 1950s, where it remained until the late-1970s when Japanese chemists devised a Frankenprocess for producing it on a large scale . . .

So, toward the goal of connecting a few dots, consider the following POP QUIZ . . .

(1) Do you think that corporate mega-farms in Mexico were feeding pigs some happy scoops of chicken, duck, and turkey poop?

(2) Do you think that corporate mega-farms in Mexico were feeding pigs some happy scoops of human poop?

(3) Do you think that corporate mega-farms in Mexico were feeding pigs various agricultural products coming from farms that routinely use strange and bizarre herbicides, insecticides, and other highly toxic chemicals, most of which are prohibited in the US?

(4) Do you think that corporate mega-farms in Mexico devote much attention to the health and well-being of the pigs they raise and slaughter?

(5) Do you think that Mexican workers at these corporate mega-farms have ready access to quality health care and always are encouraged to use best practices based on American standards?

My best guess is "Probably not!" . . .

And I think that this will be shown to be ultimate cause of the problem in the same way that similar sneaky weasel farming, animal husbandry, and food processing practices lead to strange and bizarre human diseases in our great nation--noting in particular that as the production of lettuce and other leafy vegetables shifts from the deserts of New Mexico and Arizona back to California, for the next six or so months, fresh leafy vegetables are off the menu until, once again, production moves back to the desert, where among other things, there are no nearby high-intensity cattle feedlots, since it is the desert . . .

Thanks!

JD, Seattle, WA (Sent Thursday, April 30, 2009 10:00 AM)

I like you educating our superstitious and overly visualized society. So much microscopic beauty and so little reality. The effort to move the public eye into a focused, calm, step by step "this is how we stop (it)" majority must be daunting. Perhaps our gamers can turn it into a game for us.

Patricia, CA (Sent Thursday, April 30, 2009 10:11 AM)

Viruses:

I believe that viruses are the key to the evolutionary scale. Viruses are in fact the reason humans and other animals exist at all. From the very beginning of time, viral infection of the most elemental cellular organisms have produced or induced changes at a cellular level that force cells to adapt to their environment. Unlike cellular structures, which require gene manipulation and change over time, viri quickly adapt and mutate themselves, to incorporate changes in their current environment. By manipulating the RNA, the viruses somehow coax the immune system into making physiological changes which cause the overall cellular structure of the body to adapt. Evolution is nothing more than mutation, and it itself is brought about by "viral infection" which is, itself, the very key to biological evolution as we know it.

The future key to forcing adaptation, and steering our own and other biological organisms evolutionary path, lie's in harnessing, controlling and manipulating the path of the replication and adaptation of viruses. Irradication viri is only an option, if we wish to halt our evolutionary processes. Death from viral infection is simply the natural selection and weaning out of recessive traits. Controlling, and steering viral evolution, is the key to controlling and steering our own. This is my belief.

Ken Ellis
Ms
April 30, 2009

Kendall Ellis, Southaven, MS (Sent Thursday, April 30, 2009 10:33 AM)

Bogus.

Taryn, Vancouver, BC (Sent Thursday, April 30, 2009 11:04 AM)

I thought I had swine flu, but it turned out to just be my allergies. Is there any talk of a pollen epidemic?

Corey G, Houma LA (Sent Thursday, April 30, 2009 11:05 AM)

While you explained rather well how fast a virus can mutate and how it does so the idea that a virus in so short of a time can make the rare jump between species TWICE still sound fishy. It is a rare statistical anomaly to say the least. It is my understanding also that becuase a virus mutates so quickly that this is also the reason why pandemics never reach beyond confined areas. How did this flu virus make it to New York, Canada, Europe and EGYPT(!)? What were these peoples connections with this small mexican town that contracted this? THIS DOESNT MAKE SENSE (at least without this information)

Tregan Albers (Sent Thursday, April 30, 2009 11:12 AM)

We saw where it started and we can track it. Barring a massive increase in the virulence, we have a very interesting exercise in epidemiology and education.

Check out what the pig industry is trying! "North American Flu" indeed. Some Mexican official claims it started in the US! Spinmeisters at work!

A change of subject:
1. Nature had a pay first article about the shutdown of science for the nuclear storage facility at Yucca Mountain. Heard anything about that?
2. There was also a blurb about a suit in Texas about a disease lab? Anything on that?

Wade Whitlock, Aberdeen, MD (Sent Thursday, April 30, 2009 11:42 AM)

lets not overlook the human factor in all this,becuase of where it started in a poor country with limited resorces and weak security and easy access to the us my first question is .is this virus mutation natrual or man made in our day and time lets not over look any detail ????????????????

manny new plymouth idaho (Sent Thursday, April 30, 2009 1:01 PM)

Thanks for the info, Alan, but it won't put an end to the hysteria, panic, and misinformation that people are passing on to each other.

Sara, Chicago (Sent Thursday, April 30, 2009 1:17 PM)

What is the incubation period for this virus ? is it known yet ? It seems to me that informing the public about how long they were contagious before symptoms appeared is an important piece of information to consider in evaluating who else in their circle they may have exposed. Why have none of the experts ( that i have heard so far) spoken about the incubation period given that this is an important factor governing the way a virus spreads through a community. Given that no one in the family of the child who died in Texas has caught the virus, is it possible that people become rapidly non-contagious soon after symptoms have appeared as is the case with some normal seasonal flus ? / THANKS

Phil Ioannou, Montreal, Canada (Sent Thursday, April 30, 2009 2:03 PM)

Dave Ithaca NY: "Can we imagine an STD being transmitted to an animal whos RNA is a breeding ground for genetic mutations."

LOL..how would you make the initial implication in the movie?

Thanks Allan for finally connecting the dots. I haven't seen an explanation yet in the media as to how the new strain emerges. So it's the pig that's the factory ! I didn't realize it contracted the flu from so many sources. The domesticated pig must have an inefficient immune system. It sounds to me like science should be looking at how the immune system of the pig can be corrected if that is the case.

Thomas Ashby, Calgary (Sent Thursday, April 30, 2009 2:52 PM)

This virus is everywhere... i just had a friend who is pregnant who whent to mexico just two days ago came back and she is just fine.. when she told us that almost everyone in mexico is covering up their mouth so that they don't catch the disease.. she said that she really didn't cover up her mouth and shes just fine... so is there any way that this so called ":epidemic" is not just transmited on to other people just by the breathing on them? my point is that wether this is a real epidemic or not.. it's getting everywhere and fast. but then again this is just like the time they said that htere was the bird flue it was supposed to also be an epidemic... and yet still here we are.. but then again maybe like the Aztecs craved on to a rock maybe the worls is going to end.

melina, Tucson, Arizona (Sent Thursday, April 30, 2009 4:27 PM)

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