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Anatomy of a Virus

Posted by ScuttleMonkey on Sat Feb 04, 2006 06:29 PM
from the candy-inside dept.
Biotech Science
Roland Piquepaille writes "No, I'm not talking about a computer virus here, but about a real one, the Epsilon 15, which attacks the bacterium Salmonella. By writing a few lines of computer code, biologists from Purdue University have found a way to control a high-resolution microscope. This allowed them to look inside a virus. While previous teams were able to visualize the highly symmetric outer shell of other viruses, these researchers were able to see the whole structure of Epsilon 15, including its tail, its genome and even its core. This better knowledge of viruses which attack bacteria could lead to great advances in medicine, especially when antibiotics become inefficient because of bacteria resisting them."
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  • I wonder... (Score:5, Interesting)

    by spacebird (859789) on Saturday February 04 2006, @06:35PM (#14643550)
    How long before scientists are going to try and create their own anti-bacterial virus, a la some Michael Crichton novel? From TFA: "We need a new way to attack bacteria once they mutate, and if we can employ phages to do our work for us, it could be a great advance for medicine."

    • Re:I wonder... (Score:3, Informative)

      by Anonymous Coward
      Already being tried. AFAIK the Russians had a go at using bacteriophage therapy but nothing much came of it. People have tried and failed at using phage's (viruses that infect bacteria) to try and treat bacterial infection. Might have some use but I doubt it. The host immune system tends to get in the way.

      See http://en.wikipedia.org/wiki/Bacteriophage_therapy [wikipedia.org] if you're interested

      • Re:I wonder... (Score:5, Informative)

        by artson (728234) on Saturday February 04 2006, @07:13PM (#14643687) Homepage Journal
        There was a very interesting TV special about this some seven or eight years ago as well. It had interviews with Georgian specialists in Tbilisi and an extensive history, plus their methodology. Further information here [intralytix.com] and here [biotech-monitor.nl].

        Rather than having inherent problems with the host's immune system, it seems to have fallen afoul of the Not Invented Here syndrome.

        Happily, it looks like this medical technology is coming back out of necessity.

      • Re:I wonder... (Score:5, Informative)

        by hr raattgift (249975) on Saturday February 04 2006, @09:32PM (#14644046)
        "Phage" is Greek for "eater". "Bacteriophage" is a virus that attacks bacteria.

        Viruses are almost always entirely species specific, mostly because they rely upon the structure of the cells they attack. The structures can include any of the cellular membrane or cell wall, the various DNA transcriptase and polymerase enzymes and the nuclear or chromosomal DNA itself. Bacteria are simple eukaryotic organisms so lack a number of other structures that can be abused by viruses and virus-like agents, and consequently bacteriophages are relatively simple DNA viruses.

        Bacteriophages are extremely common, particularly in bacteria-rich open water, especially in plankton-rich parts of the oceans, where there can be much more than 1E10 viruses per litre.

        A typical human being will encounter billions of viruses a day, almost none of which will challenge the active immune system -- most will be blocked by the passive systems (the skin, the mucus membranes...).

        Bacteriophage therapy bypasses the passive membranes entirely via direct application to an infected wound or by intravenous injection. Since the applied or carefully injected viruses are monoculture and highly species-specific, they do not challenge the body's primary immune response mechanisms except to the extent that any foreign protein in the blood would in dilute amounts.

        The important consideration is that the rapidly-responding innate immune system is unlikely to challenge an injected bacteriophage. The viruses cannot infect the host cells and consequently do not distress tissues (danger model and simple phagocyte chemotaxis) and are unlikely to be associated with TLRs in the innate immune system, or even encounter NODs (PAMP/PRR model).

        The adaptive immune system is much slower, which is why people are ill for several days when infected with a new pathogen. It essentially exists to memorize successful attacks against serious infectious diseases the host survives, so as to mitigate or prevent future infections by the same (or very similar) microbe.

        The plausible risks to the therapeutic bacteriophage itself when introduced into a human being with a normal immune system are mainly that the human's fever and swelling responses triggered by the bacterial infection physically keep the viruses from infecting their target bacteria, or that the human had tissue insulted by a highly similar virus (improperly injected such that it remained at high concentration, perhaps) at some time in the past.

        However, the amount of virus to be injected is tunable, and it is much more likely that in the short term the bacteriophages will find, attack and kill most of its target bacteria than they will be wiped out by the patient's immune system.

        The major practical problems with bacteriophage therapy is that they are like very narrow-spectrum antibiotics. You need to culture the bacteria in vitro and check its susceptibility to specific virus strains, which can take a full day or more. Moreover, if there are multiple strains of infective bacteria, you can "miss" with the culturing and only partially treat the patient. The time and possibility of "misses" going undetected for a while account for the popularity of wide-spectrum antibiotics.

        Unfortunately, wide-spectrum antibiotics are an evolutionary selection pressure on microbes succeptible to them... those that aren't killed because of some inheritable trait are likely to pass that trait onto their offspring. Staph. aureus, a common skin-infection bacterium, is particularly good at this, and there are strains which are resistant to very strong wide-spectrum antibiotics and even some semi-wide-spectrum ones targetting gram-positive bacteria like methicillin and vancomycin -- these are the frightening MRSA and VRSA "superbugs".

        The scary thing is that Staph. aureus bacteria are often not the bacteria being treated with wide-spectrum antibiotics like penicillin, so they are overlooked. Survivors may pass on resistance.

        Very narrow-spectr

    • Re:I wonder... (Score:4, Insightful)

      by Daniel Dvorkin (106857) * on Saturday February 04 2006, @07:49PM (#14643762) Homepage Journal
      How long before people will stop citing Crichton and other pseudo-scientific fear-mongering fiction as a reason to interfere with science and technology?

      "Forever," probably.
    • Phages, by definition, are anti-bacterial viruses! [wikipedia.org] Many bacteria have such enemies -- part of the circle of life don't ya know. Anyway, "scientists" don't need to create their own-- they just need to learn about the phages that are out there now and manage them as needed. This is an old concept known as biological control [wikipedia.org].

    • Re:I wonder... (Score:5, Informative)

      by darkmeridian (119044) <william.chuang@g ... minus herbivore> on Saturday February 04 2006, @09:03PM (#14643961) Homepage
      How long before scientists are going to try and create their own anti-bacterial virus, a la some Michael Crichton novel?

      Depends on who you ask. Some people would say we've done it [phage-biotech.com] already.

      • Re:I wonder... (Score:5, Insightful)

        by Anonymous Coward on Saturday February 04 2006, @06:55PM (#14643631)
        'Scientists' have already tried to 'reverse engineer viruses'. You can easily read viral genomes as well as insert and delete genes. Biologists have been at it for years. The question is - what do you insert or delete? It's going to take a long time before anyone can come up with an answer.

        Also the genome size has little to do with it. It's not the size, it's the content!
        • One thing worth inserting is new gene therapies (as they are developed). HIV is a particularly useful transport mechanism for this, as it's already got infestation of cells, delivery of virus RNA into cells, and suppression of the immune system down. Just take out some of the disease-causing mechanisms...

      • Re:I wonder... (Score:1, Informative)

        by Anonymous Coward
        Please read articles before citing them. This reference is about bacteria given to mice that were PRETREATED with phage. This was not a challenge study. This only points to the fact that this therapy has some potential. Preventing bacterial growth occured in vitro - ie on a petri dish.

        I agree that it probably isnt in the interests of big biotech to market such novel treatments as it takes a chunk out of their antibiotic sales. However, if it did work, I bet you some smaller biotech startup would have sprung

  • Why is this remarkable? (Score:3, Informative)

    by btavshan (699524) on Saturday February 04 2006, @06:37PM (#14643557)
    Granted, they made an improvement on existing methods used to interpret cryo-EM data, but "looking inside a virus" has definitely been done before [bbc.co.uk], and for more important viruses.

  • control those microscopes! (Score:5, Funny)

    by m-laboratories (840170) on Saturday February 04 2006, @06:38PM (#14643561) Homepage
    Fascinating. Even more surprising is that researchers from Purdue are just now learning how to control a microscope...

  • bummer ....... (Score:4, Funny)

    by Brigadier (12956) on Saturday February 04 2006, @06:44PM (#14643587)

    So they don't look like teh little rocketship diagram we have grown used to all these years.

    http://www.ucmp.berkeley.edu/alllife/virus.gif [berkeley.edu]

  • A few lines of code? wtf? (Score:5, Insightful)

    by dynamo (6127) on Saturday February 04 2006, @06:48PM (#14643602) Journal
    Is this some kind of perl golf competition? What decent software for visual recognition (it would be needed for focus) and fine machine control is going be be written in a few lines of code. I hate when reporters make up technical data like it's completely irrelevant..
    • I got the impression that it was more about proccessing data than controlling the scope. So the code would look more like a FFT or encryption algo.

    • Re:A few lines of code? wtf? (Score:4, Informative)

      by Mutatis Mutandis (921530) on Sunday February 05 2006, @11:42AM (#14646090)

      No conventional microscope is involved: A transmission electron microscope is used for this kind of work, with samples that are rapidly cooled to liquid nitrogen temperature to vitrify them. Then complex 3D image reconstruction techniques are used on the images to generate the result.

      Typically this involves finding the images of the viruses in the field of view, alignment and centering, similarity clustering of the (grainy) images, averaging of the clusters, determining their relative orientation, 3D reconstruction, and back-projection to compare the result with the input images. Symmetry helps a lot.

  • What do they mean, "could lead" ? (Score:5, Informative)

    by franois-do (547649) on Saturday February 04 2006, @07:10PM (#14643678) Homepage
    This better knowledge of viruses which attack bacteria could lead to great advances in medicine, especially when antibiotics become inefficient because of bacteria resisting them."

    As far as I know, the use of bacteriophages to fight bacterias has been mainstream for years in Russia. A recent article in Science et Vie explained this method and why it was possible to use it : there are so many different bacteriophages that they might outnumber the number of existing bacterias (a good thing, because that implies therefore a kind of competition between viruses, which means the most efficient will emerge in the long run :-) )

    The article also explained that what wad actively sought was a bacteriophage attacking Koch bacillas, because some strains are now resistant to the two antibiotics used against them (named here P.A.S. and Rimifon). Once we have located the right bacteriophages killing them, we shall be able to forget antibiotics (viruses, however, might have their own side effects too... Wait and see)

    Could be some Nobel prize in the air. I hope it will be granted to the people who deserve it, whoever they are, rather than to other teams just using the ideas of others and presenting them as their owns. The "Not invented here" policy has probaby killed enough people like that :-(

    • Re:What do they mean, "could lead" ? (Score:5, Interesting)

      by Seanasy (21730) on Saturday February 04 2006, @07:31PM (#14643729)

      Mod parent up. The discovery of antibiotics pushed phage research into the background which, I think, many biologists are realizing was a mistake. See Félix d'Herelle [wikipedia.org] for more information.

    • There have been many advances in virology, not just from the group described in the article, towards using bacteriophages (viruses which attack bacteria) to combat infection and sickness in people. This COULD LEAD to a practical solution. I have not heard of any physician using phage to treat an infection in well documented scientific study. No idea where you get your idea that this is the mainstream procedure in Russia. Here is an article referring to some of the history of phage-as-cure theories, refe
    • Remember though, the phage most likely to survive isn't going to be the one that kills its host the fastest: it's gonna be the one that can reproduce the most without decimating its local population of bacteria.

      As others have mentioned, bacteria become resistant to phages too, and a human patient's immune system will produce antibodies against the virus, rendering it much less effective.

  • Interesting work on nanoscale imaging (Score:4, Informative)

    by whitehatlurker (867714) on Saturday February 04 2006, @07:12PM (#14643685) Journal
    This work (which is in the current issue of Nature [nature.com]) reminds me of the current work on imaging the HIV virus (reported on slashdot [slashdot.org] earlier), as well as work on imaging microfossils [slashdot.org] which will soon be another rejected /. story.

    There are some movies of this work in the supplementary info [nature.com] for this article. These illustrate the various "bits" of the Epsilon-15 virus.

    It all goes to show that there is some really good work going on in three dimensional imaging of very small things. We're even seeing parts on the inside of these small things - it's just spectacular.

  • There is a debate on whether or not virii can be considered a form of life... looking at this picture, I can't help but feel it is. Like a little bug with venom, it attacks our DNA instead of our nervous system.
    • There is a debate on whether or not virii can be considered a form of life...

      Not really a debate, it depends on your point of view. What sets virii apart from bacteria is that virii can't reproduce by themselves (they abuse other organisms for that). Drop a bunch of virii in an otherwise sterile environment, and nothing much will happen. Drop some bacteria in an otherwise sterile (but suitable) environment, and they'll quickly reproduce. But hey, this is kids biology stuff...

      What it looks like under a m

      • Exactly. It's only "biological" activity is attaching to a host cell and injecting genetic instructions into it. The rest of the time, it's a dormant, yet complex protien structure. Some see it as a parasite on the cellular level since it uses the cellular machinery to reproduce itself. I think that argument has merit -- but so does the argument that it, alone, is not alive. It really is a matter of perspective. I think viruses mostlikely began as a method of transferring DNA and RNA between single-ce
  • No, the usual /. "been done before" cliche doesn't work here. The 3D images [structure.org] of the AIDS virus were produced with a completely different technique and the the AIDS virus is about 10 as big as this tiny phage. Also the jiang-phage [purdue.edu] image appears to show much more useful detail. From a virologist point of view, this is very much NEWS, especially compared to the 'news' we usually get in /. about some minor obscure variation of piece of software. Nobody yells "been done before" whenever a new Windows virus comes out...

    Also I'm sure they had a very good reason for picking this virus as a first from a virologist point of view, whereas people suggesting they should have picked something 'more important' like AIDS are probably saying that because that's the only virus they know (if they even know the difference between a virus and bacteria - not to mention phage...)

    Again a bit of insight, combined with reading TFA in question and perhaps a quick visit to Wikipedia would create much more useful reply comments... (and don't give me any of that "you must be new here" crap...)

  • Before anyone begins, the link goes straight to the article, not Roland's blog.

    Keep up the good work ScuttleMonkey.
    • I checked that first, otherwise I wouldn't have read it. I guess even a worm like Roland can come up with something useful every now and then.

      If they can do this with more virus types they may finally figure out a cure for one. That would be a first for medical science, since they have never found a cure for a single virus yet. Prevention with vaccines is a good thing but having a cure to help those already infected would be better. Think AIDS, everyone that gets it will die unless their body fights it off.
  • Or does the image on the right of this [purdue.edu] look like a new boss monster for Half/Live III???
  • Although employing or creating a virus to attack other bacteria and maybe viruses that are harmful to human beings may be a good idea for now, I'm just worried if that created virus will turn around and end up harming us somehow?

    Like the fear of how relying on computers will lead to a scenario like "The Matrix" or "Terminator", what if we become dependant on these viruses and through some stroke of nature, they end up being harmful to us?

    The following comment isn't meant to be anti-US, so please don't ta

    • Re:Will this backfire? (Score:4, Interesting)

      by Forbman (794277) on Saturday February 04 2006, @08:57PM (#14643939)
      No. Such phages have been used as a medical treatment in Russia and Eastern Europe for quite some time. There have been several popular press (Natl Geographic, SciAm, Discover) articles about the science behind them. They basically go out to a pond or other standing body of water, and bioassay the water to see what kills the bacteria they want killed. Then they try to reduce it to the active material (i.e., phage) that does it, and they go from there. It is suprisingly developed.

      These are naturally occuring phages, not genetically engineered super bugs or whatnot. Of course, they are unpatentable in the US, so no one will research them here, although the patent would be unenforcable. "We go out to so-and-so pond, centrifuge the water, isolate phage EB517, dry it and package it into gelatin capsules". Well, just about any grad student could do the same thing.... No bioreactors required, etc.

      The US way will be of course to identify a phage that attacks, say, E. Coli H:0157 (and ONLY Ec H:0157! There are too many other beneficial subtypes of E. coli in human guts that shouldn't be killed off...), and then try to do some genetic engineering to it to deliver not only the phage's package but also say a clusterbomb of penicillin or some other antibiotic, to make it "more effective". Then they could generalize from there and get a patent for using the phage for attacking E. Coli bacteria, or even for using phages as antibiotics in humans and livestock. That might get them around the lack of novelness of using phages against bacteria, which already happens in nature.

      • "The US way" (never mind that the pattern is just as likely to be used by large Swiss or Danish pharma companies as American ones) will run into the problem that there is a lot of similar work covered by patents in countries which have recently become full members of WIPO (and the European Union too) and thus by treaty have prior claim to patent protection in the USA.

        However, actually engineering a better delivery mechanism or greater effectiveness could be extremely useful, whether it is promoted by or sim
  • ... look at the hi-res photo and graphic of the virus and immediately think of a conventional high-exposive bomb? The "tail hub" looks like a proximity fuse, the "portal" looks like a screw-in cap plug, and the "dsDNA terminus" and "core" look like a primary fuse. The "dsDNA" looks like the main charge, and the "shell" looks like, well, the shell.

    All those little-bitty bombs, floating around in your blood stream, looking for a target to impact and go "BOOM!".

    Think I'll need a big scotch before I go to bed

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