Anatomy of a Virus

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."

Comments

I wonder...

[spacebird]

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...

[Anonymous Coward]

'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!

Re:I wonder...

[artson]

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 and here.

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...

[darkmeridian]

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 already.

Re:I wonder...

[hr raattgift]

"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

control those microscopes!

[m-laboratories]

Fascinating. Even more surprising is that researchers from Purdue are just now learning how to control a microscope...

A few lines of code? wtf?

[dynamo]

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..

Re:A few lines of code? wtf?

[Mutatis Mutandis]

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" ?

[franois-do]

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" ?

[Seanasy]

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 for more information.

It has NOT been done before, you insensitive clod!

[bananaendian]

No, the usual /. "been done before" cliche doesn't work here. The 3D images 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 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...)