Researchers Crack Major HIV Mystery

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Researchers Crack Major HIV Mystery

Posted by Soulskill on Friday December 20, 2013 @11:56AM 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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Both Science and Nature? by toQDuj · 2013-12-20 12:01 · Score: 2, Insightful

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.

--
Every experiment which ends in a big bang is a good experiment.
1. Re:Both Science and Nature? by rabtech · 2013-12-20 12:16 · Score: 5, Interesting
  
  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).
  
  --
  Natural != (nontoxic || beneficial)
2. Re:Both Science and Nature? by rmdingler · 2013-12-20 12:28 · Score: 1
  
  Induces cellular level suicide, if you will... It could also be a Caspase 1 inhibitor.
  
  --
  Happiness in intelligent people is the rarest thing I know.
  Ernest Hemingway
3. Re:Both Science and Nature? by reverseengineer · 2013-12-20 12:45 · Score: 1
  
  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).
  
  --
  "FDA staff reviewers expressed concern about the number of patients who were left out of the study because they died."
4. Re:Both Science and Nature? by Anonymous Coward · 2013-12-20 16:24 · Score: 1
  
  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't get published that way. You publish each piece individually. After a few years, maybe you can publish something that ties them together.
5. Re: Both Science and Nature? by MouseTheLuckyDog · 2013-12-21 03:08 · Score: 1
  
  OK. Here is a clue for you. The Gladstone Institutes is a nonprofit.
  Since this is an established drug with an established record, upwards of 90% of the testing has been done.
  So what risks are the drug companies taking?
Re:Wow by Anonymous Coward · 2013-12-20 13:03 · Score: 1

Homeopaths haven't got a fucking clue.
Re:AIDS is God's way of saying homosexuality is wr by hey! · 2013-12-20 13:03 · Score: 5, Insightful

Lesbians, by this logic, are God's chosen, since female-to-female transmission of HIV is extremely rare.

--
Post may contain irony: discontinue use if experiencing mood swings, nausea or elevated blood pressure.
Tobacco has the same effect as VX-765 by Nightlight3 · 2013-12-20 13:48 · Score: 1

Interestingly, the ancient medicinal plant, tobacco, is also caspase inhibitor, just like the promising drug VX-765 (aka "belnacasan") in that article.
1. Re:Tobacco has the same effect as VX-765 by rmdingler · 2013-12-20 14:02 · Score: 2
  
  It inhibits Caspase 3, necessary for apoptosis... I believe Caspase 1 is necessary for pyroptosis.
  
  --
  Happiness in intelligent people is the rarest thing I know.
  Ernest Hemingway
2. Re:Tobacco has the same effect as VX-765 by Opportunist · 2013-12-20 15:11 · Score: 1
  
  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.
  
  --
  We used to have a Bill of Rights. Now, with the rights gone, all we have left is the bill.
3. Re:Tobacco has the same effect as VX-765 by colinrichardday · 2013-12-20 15:39 · Score: 1
  
  Is death a caspase inhibitor?
4. Re:Tobacco has the same effect as VX-765 by Nightlight3 · 2013-12-20 16:30 · Score: 1
  
  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.
5. Re:Tobacco has the same effect as VX-765 by modmans2ndcoming · 2013-12-20 17:15 · Score: 1
  
  Junk science huh? Keep telling yourself that.
6. Re:Tobacco has the same effect as VX-765 by Nightlight3 · 2013-12-20 18:57 · Score: 3, Insightful
  
  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 (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.
7. Re:Tobacco has the same effect as VX-765 by Nightlight3 · 2013-12-20 19:09 · Score: 1
  
  It says that you should announce your great discovery to the whole world by publishing a paper and becoming famous since causing lung cancer via inhalation of tobacco smoke is still the unattained holy grail of the antismoking "science" that no one has been able to figure out how to achieve. Animals won't cooperate (half the smoking bastards are still alive after all the healthy living non-smoking ones have already gone to the happy hunting grounds), and even in the few randomized human trials that were ever done, the smoking group ended up with fewer lung cancers than the non-smoking/quit group. Check that thread mentioned earlier for literature details and discussions (especially items #1, #2, #3, #6).
8. Re:Tobacco has the same effect as VX-765 by Opportunist · 2013-12-21 00:39 · Score: 1
  
  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.
  
  --
  We used to have a Bill of Rights. Now, with the rights gone, all we have left is the bill.
9. Re:Tobacco has the same effect as VX-765 by colinrichardday · 2013-12-21 05:07 · Score: 1
  
  Of course, if the "leaving you alive" part is important, I'd rather not use tobacco.
10. Re:Tobacco has the same effect as VX-765 by sudon't · 2013-12-21 08:15 · Score: 1
  
  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 develop lung disease. If their claims were true, smokers would be dead in a year. But people don't question it, of course, because the resulting bans suit them.
  The amazing thing is that, once the anti-smoker movement got away with that one, their claims became ever more wild and unbelievable. So much so, that's it's become transparent that this is about moral disapproval, and not about science, or "saving lives." Witness the fight against e-cigs. But I'm guessing none of this will interest you.
  http://www.straightdope.com/columns/000602.html
  
  --
  -- sudon't
  Air-ride Equipped
11. Re:Tobacco has the same effect as VX-765 by Nightlight3 · 2013-12-21 09:25 · Score: 1
  
  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" or "science is settled" -- that's a scam. Another clue, especially regarding health pronouncements, is silence about experiments and exclusive focus on parroting statistical correlations on non-randomized samples, or throwing around scary numbers spewed by computer models based on such correlations. One more clue is when someone overdoes it on how solid their "science" is by comparing their scientifically sounding pronouncements to law of gravity.
12. Re:Tobacco has the same effect as VX-765 by modmans2ndcoming · 2013-12-22 11:28 · Score: 1
  
  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.
Re:Great. by antifoidulus · 2013-12-20 13:49 · Score: 4, Informative

As much as I hate to burst your "boo pharma, yay me!" bubble, the current batch of drugs, when taken properly(and that is the key) are almost as effective as condoms in preventing HIV transmission, and if used in conjunction with condoms, prevent probably about 99.9% of all infections. So yeah, obviously big pharma is trying to give everyone HIV. You cracked the case!

--
Monstar L
Re:Invest in Vertex? by sumdumass · 2013-12-20 13:52 · Score: 1

You seem to have the ability to comprehend this a bit more then I can so let me ask if this couldn't possible be a cure for HIV as well.
My though would be to extract a portion of the cells and cleans them from damaged cells you have a pure version. Then induce the self destruct while in a clean room and allow it all to implode on itself. after this is done, then simply stop the implosion, reintroduce the clean cells, and use the inhibitor to slowly bring the body back to normal. If successful, it will be HIV free.
Or am I thinking way to science fiction on this and what I said essentially the equivalent of using a transporter beam to isolate pathogens and direct them to a containment field instead of re-materializing the entire body. I'm thinking that basically it would be allowing the contamination to kill itself off and then rebuild the body without the flaws. Kind of like instead of fighting a fire one room at a time, let it burn down and rebuild a better house on the same land.
So, is HIV still the cause?? by anvilmark · 2013-12-20 15:55 · Score: 4, Interesting

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?
1. Re:So, is HIV still the cause?? by Arker · 2013-12-20 16:44 · Score: 2, Insightful
  
  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?
  
  --
  =-=-=-=-=-=-=-=-=-=-=-=-=-=-
  Friends don't let friends enable ecmascript.
2. Re:So, is HIV still the cause?? by Stickerboy · 2013-12-21 00:05 · Score: 3, Interesting
  
  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.
  
  --
  Light a fire for a man and he'll be warm for a day. Light a man on fire and he'll be warm for the rest of his life.
3. Re:So, is HIV still the cause?? by Stickerboy · 2013-12-21 00:12 · Score: 2
  
  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.
  
  --
  Light a fire for a man and he'll be warm for a day. Light a man on fire and he'll be warm for the rest of his life.
4. Re:So, is HIV still the cause?? by RDW · 2013-12-21 00:39 · Score: 4, Interesting
  
  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.
5. Re:So, is HIV still the cause?? by rmdingler · 2013-12-21 02:27 · Score: 1
  
  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?
  
  --
  Happiness in intelligent people is the rarest thing I know.
  Ernest Hemingway
6. Re:So, is HIV still the cause?? by stenvar · 2013-12-21 02:39 · Score: 1
  
  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.
7. Re:So, is HIV still the cause?? by stenvar · 2013-12-21 02:46 · Score: 1
  
  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.
8. Re:So, is HIV still the cause?? by doom · 2013-12-21 07:35 · Score: 1
  
  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.)
9. Re:So, is HIV still the cause?? by DMUTPeregrine · 2013-12-21 12:55 · Score: 1
  
  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.
  
  --
  Not a sentence!
Re:AIDS is God's way of saying homosexuality is wr by Anonymous Coward · 2013-12-20 16:35 · Score: 1

Oh really wise guy? Then how come it feels so good? Prostrate stimulation feels really nice, and you don't have to be gay to enjoy it. You can use a toy, or use a woman's fingers, or whatever. Plus, it doesn't matter what nature designed, we have moved past that.
Yess!! by formfeed · 2013-12-20 17:06 · Score: 5, Insightful

Face it, God hates fags.
Skin cancer is prove that God hates Scandinavians.
Current society is prove that God hates women.
Diabetes is prove that God hates chocolate.
Your comment is prove that God hates people.
1. Re:Yess!! by Anonymous Coward · 2013-12-20 21:35 · Score: 2, Funny
  
  And your comment is proof that God hates grammar.
2. Re:Yess!! by stoploss · 2013-12-21 16:21 · Score: 1
  
  Face it, God hates fags.
  Skin cancer is prove that God hates Scandinavians.
  Current society is prove that God hates women.
  Diabetes is prove that God hates chocolate.
  Your comment is prove that God hates people.
  I would join your insightful religion. God hates us all and is trying to damn us with ironic punishments!
Re:AIDS is God's way of saying homosexuality is wr by modmans2ndcoming · 2013-12-20 17:11 · Score: 1

God is fictional so have fun with trying to explain your bigotry in a world without randomly chosen morals written down in a 3000 year old book.
Re: AIDS is God's way of saying homosexuality is w by staalmannen · 2013-12-20 17:48 · Score: 1

more like 1600 years old. The christian bible was assembled as a political compromize in the 400s - including the classical prayer clearly stating that Jesus was tortured at the cross (a way to exclude the gnostics from the definition of christians). Apparently there are a lot of texts available that were classified as herretic back then which are the same age as those included in the NT. According to some of the Jesus was a bully in his teens using his super powers.... then again....we could just as well discus our hero-of-preference from the Marvel universe....
Re:Are we to a Trillion Dollars Yet? by chris.alex.thomas · 2013-12-20 22:48 · Score: 1

ignorant cunt
Re: AIDS is God's way of saying homosexuality is w by modmans2ndcoming · 2013-12-22 11:27 · Score: 2

I know about Helena's play thing called the Council of Nicaea. Most of the crap we get spewed out of Christians' mouths are from Leviticus though so 3000 years is accurate though the written part is a little off since it was not written down until the Jewish exile to Babylon.