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Medicine

Researchers Crack Major HIV Mystery 84

Posted by Soulskill
from the it-was-the-pathogen-with-the-candlestick-in-the-cell-membrane dept.
mrspoonsi sends this news from Scientific American: "The difference between HIV infection and full-blown AIDS is, in large part, the massive die-off of the immune system's CD4 T-cells. But researchers have only observed the virus killing a small portion of those cells, leading to a longstanding question: What makes the other cells disappear? New research shows that the body is killing its own cells in a little-known process. What's more, an existing, safe drug could interrupt that self-destruction, thereby offering a way to treat AIDS. The destructive process has caught scientists by surprise. 'We thought HIV infects a cell, sets up a virus production factory and then the cell dies as a consequence of being overwhelmed by virus. But there are not enough factories to explain the massive losses,' says Warner Greene, director of virology and immunology at the Gladstone Institutes, whose team published two papers today in Science and Nature describing the work. Greene estimates 95 percent of the cells that die in HIV infections are killed through pyroptosis, so the findings raise hope for a new type of treatment that could prevent HIV from progressing into AIDS. 'Inhibiting activation of the immune system is not a new concept, but this gives us a new pathway to target,' says Robert Gallo. And in fact, a drug already exists that can block pyroptosis."
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Researchers Crack Major HIV Mystery

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  • by toQDuj (806112)

    This is how you milk science. I won't contest that it is incredibly useful, but the decision to publish in *both* Nature and Science shows the direction science is heading in. All for papers.

    • by rabtech (223758) on Friday December 20, 2013 @08:16PM (#45750547) Homepage

      If you don't publish papers, you don't get funding. Sucks, but that's what we get for budget cut after budget cut, tax cut, after tax cut.

      The big question appears to be if the latent infected cells can clear or deactivate HIV, or if they'll happily activate, travel to the site of an infection of some other kind, then start spewing HIV everywhere.

      This process is basically cells realizing they are being infected (virus) or eaten (bacteria) by a foreign organism, and responding by killing themselves and spewing massive amounts of chemicals that alert the immune system to the problem. Normally, this recruits other immune cells to the site and is probably the right strategy 99% of the time. The problem is when the infected cells are immune cells themselves, their death just recruits more immune cells to an area with a higher chance of picking up HIV. What they found was that the body's stockpile of immune cells in the spleen, etc (normally dormant, awaiting an infection) get infected by HIV, but don't replicate the virus due to being inactive, however they are active enough to sense the virus in their DNA and kill themselves before repair mechanisms can remove or deactivate the virus genes.

      The drug mentioned apparently shuts down or reduces this pathway, opening you up to a higher risk of bacterial infection but slowing or stopping the massive die-off of immune cells (assuming they are able to clean themselves up).

      • Induces cellular level suicide, if you will... It could also be a Caspase 1 inhibitor.
        • Induces cellular level suicide, if you will... It could also be a Caspase 1 inhibitor.

          That's just what it is: VX-765 is belnacasan, a caspase 1 inhibitor (a drug target for epilepsy for its role in releasing inflammatory cytokines).

    • by Anonymous Coward

      Did you read the papers? They are separate and independent papers. The first three authors, ie, the people who actually did the experiments, are different people. You can't put too much into a single paper. First, there are page limits, and secondly, It's too difficult to get large papers through the peer review process. Papers need to be short focused and in bite sized pieces, where there are experts on the topic. You can't take two separate things, and then try to tie them together into one paper. It won'

  • Interestingly, the ancient medicinal plant, tobacco, is also caspase inhibitor [atsjournals.org], just like the promising drug VX-765 (aka "belnacasan") [medkoo.com] in that article.

    • It inhibits Caspase 3, necessary for apoptosis... I believe Caspase 1 is necessary for pyroptosis.
      • Tobacco smoke has a broad, multilevel anti-inflammatory effects, from inflammatory controls in vagus center, then via the upregulation of corticosteroids, down to stimulation of anti-inflammatory cellular alpha-7 receptors. This includes inhibition of the same inflammatory cytokines (IL-1beta, IL-18) [wiley.com] as done by VX-765.

        Interestingly, nicotine only partially accounts for these anti-inflammatory effects, while some unknown components of the full tobacco smoke yield additional protection. For example in a rela [arthritis-research.com]

        • Junk science huh? Keep telling yourself that.

          • by Nightlight3 (248096) on Saturday December 21, 2013 @02:57AM (#45752219)

            Epidemiology by itself isn't a junk science. It crosses into junk science when someone leaps from observed statistical associations on non-randomized samples to wishfully ($$$) declaring causal relations. Such associations are at best a hint that there may be causal relation, but one needs hard science, such as randomized trials or animal/human experiments to find out what kind of links (e.g. causal or protective/therapeutic) connect those correlated variables.

            That's how it is done in normal science, you use statistical hint to make hypothesis that is followed up with hard science. But antismoking "science" is stuck on the same hint since 1950.

            And it is not for lack of trying hard science. There were thousands of experiments done since then. The problem was that they all went the "wrong" way -- the smoking animals live longer, perform better on cognitive tasks, get cancers less often, etc. What can poor scientific mercenaries do, when their bosses want the opposite result, but stick with what works, parrot the statistical hints disguised as "science." This was so unusual pattern that already in 1958, the father of modern statistical methods, famous British mathematician R. A. Fisher noticed it and wrote [york.ac.uk] (pdf; this article also contains a very readable exposition of the sample randomization topic):

            "Most of us thought at the time, on hearing the nature of evidence, which I hope to make clear a little later, that a good prima facie case had been made for further investigation. But the time has passed, and although further investigation, in a sense, has taken place, it has consisted largely of the repetition of observations of the same kind as those which Hill and his colleagues called attention to several years ago. I read a recent article to the effect that nineteen different investigations in different parts of the world had all concurred in confirming Dr. Hill's findings. I think they had concurred, but I think they were mere repetitions of evidence of the same kind..."

            Yet, the antismoking "science" still rests its case squarely on the same kind of soft/junk science that Fisher objected to over half a century ago.

          • by sudon't (580652)

            Junk science huh? Keep telling yourself that.

            The science linking smoking to lung disease is pretty clear, not to mention common-sensical. Inhaling large amounts smoke of any kind is not going to be good for you. OTOH, the so-called science behind the second-hand smoke scare is inconclusive, at best. Nor does it pass the common-sense test. You would think that people would question a claim that minute exposure to tobacco smoke could be dangerous, when smokers inhale huge lungfuls of smoke, all day, every day, for decades, and yet only 70% eventually de

            • I don't want to breath in your shit. Its simple courtesy to not bother people in a closed environment with your nasty smelling smoke.

    • Great, so now people may decide whether they die from aids or cancer.

      It's just like with the elections. You have the free choice.

      • Not really. The association between tobacco smoking and lung cancer is, like the above link to rheumatoid arthritis, only statistical association on non-randomized samples, hence it only shows that tobacco smoking and lung cancer are in the same web of causes and effects, but not what the nature of those links is. For that you need hard science. As with the arthritis, the hard science (animal experiments, randomized trials), shows exactly the opposite -- tobacco smoke is protective against lung cancer.

        For e

        • Well, maybe they should next time use animals with a lifespan longer than a gnat next time. It's not like you get to die of lung cancer at 25 when you started smoking when you were 20. Usually, people tend to die around age 50 or so.

    • Is death a caspase inhibitor?
      • In that sense, death is pain and suffering inhibitor too, including AIDS, except you don't get to enjoy the fruits. But here we talking about medicinal substances which can block the damaging cytokines while leaving you alive.

        • Of course, if the "leaving you alive" part is important, I'd rather not use tobacco.
          • The responses illustrate how easily most people, especially the educated ones, fall for scams if they are wrapped into scientific language. That's why there are so many of them, especially from sickness industry since that's where people are the most ready to part with their money.

            One little clue to help you recognize a pseudo-scientific scam is when you hear a pronouncement from high up "debate is over" [surgeongeneral.gov] or "science is settled" -- that's a scam. Another clue, especially regarding health pronouncements, is

  • by anvilmark (259376) on Friday December 20, 2013 @11:55PM (#45751623)

    HIV only kills ~5% of the T-cells.
    Newly discovered pyroptosis pathway kills the other 95%
    This is a radical departure from the accepted mechanisms of how HIV works. Pyroptosis can be triggered by a boatload of different inflammatory processes, I'll be looking forward to their smoking gun that HIV is the cause.
    With all the research money poured into HIV research, it's taken them 20 years to notice this?

    • Re: (Score:3, Insightful)

      by Arker (91948)
      It's a good question. All I see in this paper is fresh discovery of the same facts that were well known among skeptics like the Perth group back in 1990s. Is it really such a bizarre virus that acts like no other virus, kills like no other virus, and manages to hide the way it works so well that decades of research still leave us guessing? Or is it just a weak virus that cannot survive inside an uncompromised immune system and thus serves as a great diagnostic for immune problems that it does not actually c
      • by Stickerboy (61554)

        It's a good question. All I see in this paper is fresh discovery of the same facts that were well known among skeptics like the Perth group back in 1990s. Is it really such a bizarre virus that acts like no other virus, kills like no other virus, and manages to hide the way it works so well that decades of research still leave us guessing? Or is it just a weak virus that cannot survive inside an uncompromised immune system and thus serves as a great diagnostic for immune problems that it does not actually cause?

        It's a horrible question. Treating the HIV infection with anti-HIV medications can for the most part prevent or regress the syndrome of AIDS. If it was just a "great diagnostic for immune problems that it does not actually cause", treating and suppressing the HIV infection should be 100% ineffective in helping the patient.

      • by RDW (41497) on Saturday December 21, 2013 @08:39AM (#45752907)

        Or is it just a weak virus that cannot survive inside an uncompromised immune system and thus serves as a great diagnostic for immune problems that it does not actually cause?

        You are confusing legitimate high quality research with HIV denialist fiction. This work describes a new and potentially very important mechanism by which HIV infection and partial replication lead directly to cell death. Uninfected cells are not dying. Uninfected patients are not developing AIDS. Unfortunately, HIV denial is one of the more harmful conspiracy theories, leading to (e.g.) hundreds of thousands of avoidable AIDS deaths in South Africa when scientifically uninformed officials were in charge of health policy.

      • by stenvar (2789879)

        I'm not sure what gives you the idea that HIV is biologically unique or bizarre. There are lots of immune deficiencies, retroviruses, and persistent infections, both in animals and humans.

        • by doom (14564)

          I'm not sure what gives you the idea that HIV is biologically unique or bizarre

          Yeah, it some ways it's similar to influenza.

          There's was a something I saw recently about how new work on HIV-vaccines might actually lead to something like a permanent flu shot.

          (Funny, I'd forgotten about the HIV-denialists. I had the vague feeling that one had faded away... No such luck.)

    • by Stickerboy (61554) on Saturday December 21, 2013 @08:05AM (#45752817) Homepage

      HIV only kills ~5% of the T-cells.
      Newly discovered pyroptosis pathway kills the other 95%
      This is a radical departure from the accepted mechanisms of how HIV works. Pyroptosis can be triggered by a boatload of different inflammatory processes, I'll be looking forward to their smoking gun that HIV is the cause.
      With all the research money poured into HIV research, it's taken them 20 years to notice this?

      Hi! Your comments are a sterling example of the dangers that having just a little knowledge in a certain field poses. As a doctor who has worked in an HIV clinic, let me give you the best practical proof for your reinventing of the wheel. Take an AIDS patient who is sick with an opportunistic infection. Cure the infection, and start the patient on a good regimen of anti-HIV medications. In most patients who aren't too far gone, their immune systems will rebound, and as long as they're compliant with taking their meds, the odds are they will never reexperience the practical consequences of an AIDS diagnosis.

      Testing positive for HIV used to be a death sentence. Now with current anti-HIV meds, HIV can be relegated to a chronic illness less burdensome, and less deadly, than type 2 diabetes mellitus. Do you understand that? Treatment of an HIV infection can prevent the onset of AIDS, a clinical syndrome.

      If you want a better proof, have a scientist inject you with HIV virus. Make a journal, and see what happens in 5 years.

      • Why have so many diseases found a comfortable niche as chronic, but treatable?

        Did we not, in years gone by, use to occasionally create cures and preventative vaccinations?

        • There are many diseases out there. Some are easy to cure, some hard. Just because we cured some diseases doesn't mean it's equally easy to cure the others. In years gone by we cured the "low-hanging fruit," and are now working to cure the difficult diseases.
    • by stenvar (2789879)

      With all the research money poured into HIV research, it's taken them 20 years to notice this?

      Because medical research is hard. What you ignorantly refer to as "noticing" requires a lot of skill, insight, and hard work to discover.

      And this doesn't invalidate prior approaches to HIV treatment: targeting the virus has been rational and effective, no matter how it ultimately does its damage.

Facts are stubborn, but statistics are more pliable.

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