November 6th, 2010

A still from a video from the Molecular Biology Laboratory, Cambridge, England. Download from here (it´s too big to upload to the RBC website).

The movie illustrates what looks like a fundamental discovery in viral immunology.

British science jounalists are uniformly under-reporting it as a future fix for their common colds, but it´s much more than that: viral dysentery and HIV are mass killers. Dr Leo James (Nobel surely in the post, eventually) and his team have overturned a dogma that once viruses enter a cell, they take it over. They found out that in fact, if extracellular antibodies – the yellow stick figures – latch on to the virus, they accompany it into the cell, where they are in turn latched on to by proteins called TRIM-31 (the turquoise stick figures), which call up proteasomes (the orange and-brown drums), which eat the virus. Bingo. Knowing how it works is half the battle, and virologists everywhere have suddenly got much more effective.

Note to Rep. Darrel Issa: this is a discovery by foreign scientists, paid for by British taxpayers and charities, which will eventually save American lives. ¨Science in one country¨ is, and always has been, an absurd policy. Fundamental research is a contribution to a global project of humanity; a reimbursement by each generation of the benefits it has received from its ancestors in the only possible way, viz. an investment in the welfare of its descendants. Logically, it should be funded through the UN. Not going to happen, but the current national basis involves scientists in spinning a largely fanciful tale of appropriable technological spinoffs to the likes of Issa.

A lesser threat to Americans has also just been taken away entirely: rinderpest, a lethal viral disease of cattle, close cousin to and likely ancestor of human measles.

Credit: Texas A&M University; the photo is apparently from an outbreak in South Africa in 1897.

The FAO has announced its de facto worldwide eradication (the formal declaration will be a bow-tie event next year); only the second disease of any sort to have been bottled up definitively. It´s true that rinderpest never established itself in the New World, but the risk has always been there, and that and the prevention measures are real costs. Again, a freebie for American taxpayers from other people´s efforts.

The drive for smallpox eradication was in fact proposed in 1958, during the Cold War, by a deputy Soviet Minister of Health, the virologist Professor Viktor Zhdanov. Zhdanov was a real scientist, not to be confused with the repellent Stalinist inquisitor Andrei Zhdanov. I speculate that as viruses and bacteria do not evolve by sexual inheritance, research on them did not fall foul of Lysenko´s war on Mendelian genetics and Darwinism.

The eradication movies, whether for viruses or parasites, play out in agonizingly slow motion.

  • Guinea worm (dranunculiasis) : campaign started 1986 by Carter Centre; down from ca. 3.5 million cases to 3,910 reported cases in four Sahel countries:. eradication predicted: ¨a few years yet¨ (WHO).
  • Polio: campaign started 1988; down to 483 new cases in 2001 but has since gone back up and plateaued at around 1,500 a year; current eradication target: none given.
  • Elephantiasis (lymphatic filariasis): campaign started 1993; eradication target : 2020 (treatment of infected people takes seven years).
  • Measles: campaign started in 2001 for 90% reduction; eventual eradication agreed by WHO in 2010, no target date set.

Campaigns to eradicate hookworm, malaria, yaws, and yellow fever have been abandoned, or rather suspended until we have better technology. The Carter Centre says that it is feasible with current knowledge to eradicate mumps, rubella, and infection from pork tapeworms (cysticercosis), but the global public health community hasn´t signed up yet.

One of the most moving museums I´ve ever visited is the tiny one in Edward Jenner´s old garden in the Gloucestershire countryside at Berkeley. It was a long, winding road between James Phipps, the boy Jenner vaccinated in 1796, and Ali Maow Maalin, the Somali cook who was the last diagnosed victim in 1977. Both Phipps and Maalin survived. The hide of Jenner´s other involuntary collaborator, Blossom the cow, hangs on a wall at St. George´s medical school in London.

PS: several commenters on Harold´s post could do worse than consider the moral example of young James and Blossom. Neither had a real choice to contribute to the global public good, but they still did the right thing.

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9 Responses to “Virus movies”

  1. Total eradication of hookworm would be something of a tragedy, since it seems to be effective in treating refractory asthma and allergies ( But confining it to a lab and studying the mechanism by which it works would be a worthy goal.

  2. [...] This post was mentioned on Twitter by MovieMan, said: Book News: Virus movies: A still from a video from the Molecular Biology Laboratory, Cambridge, England. Downlo… [...]

  3. Eli says:

    Very cool. Two thoughts: one, some bacteria do exchange genes through “sexual conjugation”, right?, and two, the Republican party probably gets $5 million in alcohol and prostitutes in a month from lobbyists. Which come to think of it are a lot like bacteria.

  4. This is a wonderfully clear exposition of an important but difficult topic. I hope your explanation is accurate, because I am relying on it. I’ve read newspaper articles which didn’t explain much except that antibodies are important inside cells too.

    I think that the immensely important discovery of prof James et al is more relevant to rotavirus than to HIV. Viruses come in two types — viruses with envelopes and viruses with protein capsids. The cold virus(es) and rotaviruses have protein capsids. They have nucleic acid and surrounded by protein. The whole virus particle enters cells.

    Other viruses have cell membranes similar to the membranes of our cells — the membrane is made of phospho-lipids with proteins sticking through it. They infect when the virus menbrane fuses with one of the target cells membranes (typically inside a lysosome which is a little membrane bag full of acid and proteases and stuff which buds off of the main cell membrane heading into the cell).

    Inside the virus’s membrane there is a structure like that of a protein capsid virus with protein and nucleic acid which enters the cell. The problem is that the outermost part of the virus (the membrane with proteins sticking through it) is separated from the part which takes over the cell (the nucleic acid and protein stuck together). I fear that this means that antibodies stuck to the virus will remain as part of the lysosome while the rest of the virus floats off to infect the cell.

    Rotaviruses are little protein RNA particles which enter cells whole and should bring the antibodies in along with the RNA and the proteins which work as enzymes replicating the RNA and transcribing it to make messenger RNA which tricks our ribosomes into making new virus proteins. The antibody TRIM-31 proteasome mechanism should work with rotaviruses.

    But I doubt it does much against HIV.

    I stress that I am not a virologist, or an immunologist, or a cell biologist, so don’t confuse this comment with an expert opinion.

  5. James Wimberley says:

    Robert: don´t rely on me or UK science reporters, rely on the article or at least the handouts!
    James et al did indeed use adenovirus as a non-enveloped virus. So maybe HIV is a long shot. But it doesn´t look as if the virologists rule it out: ¨Crucially, encapsulating immunity within host cells means that every infection event is an opportunity for neutralization.¨ (From their article, my italics.) Maybe you can get HIV antibodies into cells by piggybacking on an adenovirus, or something.

    Rotaviruses kill 500,000 children a year worldwide, so a cure or vaccine for them would be a colossal payoff already.

  6. James Wimberley says:

    Frank Schmitt: one of the approaches to helminthic therapy for autoimmune diseases – the one used by the guy in the BBC programme who cured his ulcerative colitis – uses pig hookworms, which can´t establish themselves permanently in humans. But if it turns out that the human ones are better, you can surely both eradicate them in practice in the African wild and keep stocks for therapy. Medical students and winos could earn a few bucks by acting as hosts.

    To coin a phrase: we are no such thing as a free lunch.

  7. James Wimberley says:

    Eli: bacterial comjugation? Wikipedia says the analogy to sexual reprodution is only loose. It wasn´t dicovered anyway until 1946, when Lysenko´s star was already fading a bit. Whatever: the mechanism isn´t Mendelian, which requires that sexual recombination is the only way of redistributing genes. At first sight conjugation fits Lysenko´s Lamarckianism, the idea that living things can pass on adaptative traits acquired by living in a particular environment (eg giraffes stretching their necks to reach high branches). Either way, he would have left the virologists and bacteriologists alone.

  8. Aardvark Cheeselog says:

    Robert Waldmann: my last virology class was over 20 years ago but I can expand on your description a little bit: enveloped viruses generally (always?) do have a capsid, just like naked viruses. The whole membrane-fusion business is a higher-tech way of getting it into the host cell. Which leads me to suspect that the discovery is not likely to be of immediate use against HIV, unless somehow antibodies against the capsid can be gotten through the virion’s envelope before it fuses.

    See for a description that matches my obsolete training pretty well.

  9. Brett Bellmore says:

    “unless somehow antibodies against the capsid can be gotten through the virion’s envelope before it fuses.”

    Hypothetically, you could deliver them straight to the interior of the cell by packaging them in liposomes, and let them connect up to the capsid once inside. The key discovery here is that being labeled with antibodies actually means something inside the cell, that the cell has a mechanism for destroying viruses that have already made it inside. Rather than it being too late once the virus enters the cell.