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Biotech News Science

Three-Dimensional Structure of HIV Revealed 189

Mutatis Mutandis writes "The BBC is reporting that a team of scientists from Oxford, Heidelberg and Munich has created the first accurate three-dimensional images of the HIV virus. The virus was found to have an average diameter of 125 nanometers, well below the wavelength of visible light. In the past the structure of viruses with a regular structure has been produced by 3D reconstruction techniques that work on a set of electron microscopy images of different viruses, but the irregular structure of HIV does not allow this. Scientists have now used a tomography technique that employs a series of images taken from a single virus, somewhat similar to the better known X-Ray CAT scan, but on a quite different scale." Structure also has a video of the 3-d rendering available for download. Relatedly an anonymous reader writes "A research team at Brown University has genetically modified bacteria found in yogurt so that the bugs produce a protein proven to block HIV infection in monkeys. The results offer hope for a microbicide that can prevent the spread of HIV, which now affects about 40 million people."
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Three-Dimensional Structure of HIV Revealed

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  • by c0dedude ( 587568 ) on Wednesday January 25, 2006 @03:46AM (#14555471)
    Yes, HIV causes AIDS. To think otherwise puts millions in danger. The idea that it does not has been rejected for years by mainstream science and is perpetuated by a self-denying HIV infected population, not by science.
  • by putko ( 753330 ) on Wednesday January 25, 2006 @03:54AM (#14555499) Homepage Journal
    Well what about this stuff (these guys are respectable, so WTF??): http://www.virusmyth.net/aids/controversy.htm [virusmyth.net]

    * Dr. Kary Mullis, Biochemist, 1993 Nobel Prize for Chemistry:

    "If there is evidence that HIV causes AIDS, there should be scientific documents which either singly or collectively demonstrate that fact, at least with a high probability. There is no such document." (Sunday Times (London) 28 nov. 1993)

    * Dr. Heinz Ludwig Sänger, Emeritus Professor of Molecular Biology and Virology, Max-Planck-Institutes for Biochemy, München. Robert Koch Award 1978:

    "Up to today there is actually no single scientifically really convincing evidence for the existence of HIV. Not even once such a retrovirus has been isolated and purified by the methods of classical virology." (Letter to Süddeutsche Zeitung 2000)

    * Dr. Serge Lang, Professor of Mathematics, Yale University:

    "I do not regard the causal relationship between HIV and any disease as settled. I have seen considerable evidence that highly improper statistics concerning HIV and AIDS have been passed off as science, and that top members of the scientific establishment have carelessly, if not irresponsible, joined the media in spreading misinformation about the nature of AIDS." (Yale Scientific, Fall 1994)

    * Dr. Harry Rubin, Professor of Molecular and Cell Biology, University of California at Berkeley:

    "It is not proven that AIDS is caused by HIV infection, nor is it proven that it plays no role whatever in the syndrome." (Sunday Times (London) 3 April 1994)

    * Dr. Richard Strohman, Emeritus Professor of Cell Biology at the University of California at Berkeley:

    "In the old days it was required that a scientist address the possibilities of proving his hypothesis wrong as well as right. Now there's none of that in standard HIV-AIDS program with all its billions of dollars." (Penthouse April 1994)

    * Dr. Harvey Bialy, Molecular Biologist, former editor of Bio/Technology and Nature Biotechnology:

    "HIV is an ordinary retrovirus. There is nothing about this virus that is unique. Everything that is discovered about HIV has an analogue in other retroviruses that don't cause AIDS. HIV only contains a very small piece of genetic information. There's no way it can do all these elaborate things they say it does." (Spin June 1992)

    * Dr. Roger Cunningham, Immunologist, Microbiologist and Director of the Centre for Immunology at the State University of New York at Buffalo:

    "Unfortunately, an AIDS 'establishment' seems to have formed that intends to discourage challenges to the dogma on one side and often insists on following discredited ideas on the other." (Sunday Times (London) 3 April 1994)

    * Dr. Gordon Stewart, Emeritus Professor of Public Health, University of Glasgow:

    "AIDS is a behavioural disease. It is multifactorial, brought on by several simultaneous strains on the immune system - drugs, pharmaceutical and recreational, sexually transmitted diseases, multiple viral infections." (Spin June 1992)

    * Dr. Alfred Hässig, (1921-1999), former Professor of Immunology at the University of Bern, and former director Swiss Red Cross blood banks:
  • by soundofthemoon ( 623369 ) on Wednesday January 25, 2006 @04:02AM (#14555522)
    This isn't a new idea, that HIV isn't the cause of AIDS. You get these kind of weird ideas when laymen try to apply "common sense" in place of domain knowledge. HIV is a retrovirus that attacks the immune system, so it has unusual characteristics and effects compared to most other viruses.

    A common argument goes that when a person is most sick with AIDS they have a low HIV load, which "doesn't make sense", since in all other viral infections the viral load is high when the infection is acute. However, since HIV destroys the immune cells in which it grows, you can actually see a low viral load as the infection progresses because it has no place left to grow. But by then the immune system is no longer effective at fighting off other infections and the infected person gets very sick.

    As for the procedures that were followed, I think researchers have done a very good job at studying HIV and its transmission. However no ethical researcher would intentionally infect a human with a fatal disease, and HIV is specific to humans. SIV (a related virus that infects simians) has also been studied and it's pretty well accepted by now that SIV causes an AIDS-like condition in monkeys, and that HIV is actually the agent that causes AIDS in humans.
  • Re:3d modeling (Score:3, Informative)

    by Mortiss ( 812218 ) on Wednesday January 25, 2006 @04:02AM (#14555523)
    This image cannot be used for structural modelling of potential inhibitors because its resolution is too low. You need an x-ray crystal structure with Angstrom resolustions to be able to do this (these images have resolution of ~4 nm which is still very impressive for electron microscopy)
    However, partial structures of HIV surface proteins (gp120 and gp41) are available but I am not sure if they have been used to model potential inhibitors.
    On related note there is a newely FDA licensed inhibitor compound (T20 peptide) that blocks the function of fusion subunit of HIV surface protein (gp41) and it has been developed thanks to the structural information on this protein.
  • by c0dedude ( 587568 ) on Wednesday January 25, 2006 @04:10AM (#14555550)
    How many peer reviewed journals are cited above? ZERO!
    Here's an easy to read summary of the real evidence: http://www.avert.org/evidence.htm [avert.org]
    And a more detailed summary: http://www.niaid.nih.gov/factsheets/evidhiv.htm [nih.gov]

    Here are some of the proven, reviewed, science backed theories, quoted from the NIH site above:

    "AIDS and HIV infection are invariably linked in time, place and population group."

    "Many studies agree that only a single factor, HIV, predicts whether a person will develop AIDS."

    "HIV can be detected in virtually everyone with AIDS."

    "Newborn infants have no behavioral risk factors for AIDS, yet many children born to HIV-infected mothers have developed AIDS and died."

    "The HIV-infected twin develops AIDS while the uninfected twin does not."

    These are peer reviewed scientific theories. Anyone can cast doubt on them, but to do so with such little evidence is irresponsible, especially considering the gravity of the disease. No serious journal proposes that AIDS is not caused by HIV.
  • Re:Cool (Score:5, Informative)

    by deglr6328 ( 150198 ) on Wednesday January 25, 2006 @04:15AM (#14555567)
    right now [giantmicrobes.com].
  • Short answer: Yes. (Score:5, Informative)

    by jd ( 1658 ) <imipak@ y a hoo.com> on Wednesday January 25, 2006 @04:19AM (#14555577) Homepage Journal
    Long answer: There have been plenty of studies with Rhesus Monkeys that do indeed show that injecting the HIV virus does cause AIDS. The alternative theory was devised by a French scientist whose name escapes me, but appears to have been motivated more for fame, glory and nationalism than anything. The argument is often repeated, but repeating it doesn't make it valid, it simply makes it heard more often.


    With the HIV virus, we know the mechanism by which infection originates, spreads, disables the immune system, etc. There isn't a vast amount we don't know. The HIV virus took a while to isolate and sequence, but when compared to other viruses, it was damn quick.


    What we don't know is the history prior to the first recorded case, whether or not a guy in England really DID somehow eliminate the HIV virus from his body (he refuses to get re-tested after he got a negative), why some people do not produce HIV antibodies when exposed to the virus (are they immune, as some claim, or is their immune system just not capable of detecting it?) and how a virus so astronomically unstable can function (one problem with producing a vaccine is that de-activated HIV can re-activate itself, becoming extremely dangerous).


    Now, there are indeed cases where medical science seems to have jumped to conclusions. BSE and CJDnv are supposedly caused by prions, but infected brain tissue retains its ability to transfer the deadly agent after being cooked at high temperatures. Also, it is unclear how proteins (a prion is just a protein) can get through the stomach wall AND the blood-brain barrier in order to cause damage.


    Even in this case, although there are plenty of skeptics of the prion theory, I know of nobody who is seeking to ridicule the work. Rather, they are pursuing their own lines of enquiry with some measure of dignity. That's how you can tell the good from the great. The merely good will sometimes bolster their egos by proclaiming themselves the One True Word, denouncing everyone else. The great let the results speak for themselves.

  • Tomography (Score:2, Informative)

    by tchiwam ( 751440 ) on Wednesday January 25, 2006 @04:24AM (#14555595) Homepage
    It would be nice to know what methods they used for tomography. With the latest methods it can be possible to get better Tomography resolution than the measurment device has by itself. The geometry of the measurement itself would be great to know too.

    Also it is today possible to solve many million unknowns by using stocastic inversion, something that was taking ages and truly huge amount of memory not so long ago, can now be done on a deskside.

    For example it is possible to reconstruct the shape of an asteroid using only a single value like light intensity or radio signal intensity over a period of time. That would be like a 1x1 sensor size with multiple projection and arbitrary geometry.

  • Bullshit (Score:5, Informative)

    by Stickerboy ( 61554 ) on Wednesday January 25, 2006 @04:40AM (#14555643) Homepage

    Look, all these guys have at one time or another been respectable, but the truth is, HIV is a well-characterized virus with dumptrucks full of money poured into research into how and why it works.

    The fact that I can pick out one name, Harvey Bialy, google him and find out he's currently on South Africa's payroll (who deny pregnant mothers with AIDS AZT or other basic anti-HIV drugs, btw) says volumes.

    HIV's genome has been sequenced and studied, and scientists know in general how it works. Instead of copying and pasting one of my microbiology textbooks, I'd suggest looking up the "HIV" Wikipedia entry - it's got a good summary of the parts listed. You might try the "AIDS reappraisal" entry, where all the bullshit claims are addressed.

    Have you taken a look at what all those "respected scientists" are actually saying? It sounds a lot like the utter crap being spewed by the "respectable scientists" employed by the Creationism... er, I mean the Intelligent Design idiots. "There's problems... there's questions..." Not a single decent counter-hypothesis as to the origin of AIDS or why the volumes of peer-reviewed AIDS research is WRONG.

    If they were truly so adamant that HIV did not cause AIDS, there would be a simple way to prove it once and for all: they should all get together and perform a witnessed scientific study whereby they all inject a reasonably large dose of HIV virus into their bloodstreams and monitor the results. Dr. Barry Marshall, in fact, won a Nobel Prize for proving that H. pylori causes GI ulcers by doing just that.

    Now to answer your original claims, that some people with HIV do not get AIDS and some people with AIDS do not have HIV, both of them have answers (the Wikipedia page, in fact, covers the 1st one). Some people have genetic mutations to coreceptors that HIV needs to infect CD4+ T-cells (CCR5 and CXCR4 being the 2 most common). Those mutations render the virus unable to infect the cells without further mutation of the virus. This is, in fact, a huge avenue of biomedical research - my medical school is participating in toxicology trials for a proposed drug using this.

    The other claim, that some patients with AIDS do not have HIV is a very rare autoimmune condition. Through molecular mimicry or another similar means, a patient's CD4+ immune cells are targeted for destruction by the patient's own immune system, which leads to the loss of those cells and the development of AIDS. Nobody knows why yet (this is VERY rare), but it probably is caused by cross-reaction with similar antigens from a foreign source (bacteria, virus, fungal, etc.). The body has a bad propensity to attack itself - look up rheumatoid arthritis, lupus, Goodpasture's, Hashimoto's, or late-stage Lyme Disease among others.

  • by Mostly a lurker ( 634878 ) on Wednesday January 25, 2006 @05:06AM (#14555713)
    No, the idea is a microbicidal cream that will form a barrier against HIV. I must admit to confusion over why this would be such a great breakthrough. It is unlikely to provide better protection than a condom. I guess women could use it where their partners refused to use a condom. Perhaps one idea will be to use it in conjunction with a condom in the way once recommended with nonoxynol-9. Note that creams [hivdent.org] and gels [washingtonpost.com] with similar objectives are already being evaluated (supported by the Gates Foundation and others).
  • by Anonymous Coward on Wednesday January 25, 2006 @06:10AM (#14555927)
  • by Anonymous Coward on Wednesday January 25, 2006 @07:56AM (#14556233)
    Where to start ?

    First. HIV is NOT an opportunistic infection.

    An opportunistic infection is an infection that gets the opportunity because of a weakened condition of the immune system. HIV is an infection that attacts and weakens the immune system, so that it leaves its victim viable to opportunistic infections (such as Herpes, or many diseases that were considered gone and conquerored). AIDS is the
    condition of having such a weak immune system because of HIV, and that you die BECAUSE OF opportunistic infections.

    Thus: HIV attacks immune system. Patient is uprotected against opportunistic infections. Patient dies.

    With respect to antiviral therapy. How do you explain the fact that since the introduction of antiviral therapy in the Western society, morbidity and death rates have gone down drastically, while people that do not receive therapy but are diagnosed with HIV, die (like in Subsaharan Africa ?) at quick rates ?

    The truth is, yes, most antiviral drugs have side-effects. In fact, most drugs have side-effects. But these drugs save lifes (in the Western world). Because of advances in drug efficacy and regime potency, most people that start now with therapy and adhere to their drugs and whose HIV as a consequence does not develop antiviral resistance, see
    a rebound in their immune system (measured by CD4 cell count) ! Many studies have confirmed that over and over again.

    Stop fooling yourself and do something constructive.

    Regards,
    anonymous HIV researcher.
  • Western Blot (Score:3, Informative)

    by Anonymous Coward on Wednesday January 25, 2006 @09:47AM (#14556812)
    Kary Mullis is saying more research needs to be done. And he has some good points that HIV isn't always the cause of AIDS-like symptoms, so additional testing must be carried out before giving all kinds of anti-HIV drugs to a patient with AIDS symptoms.

    In my opinion, he does not have proof that HIV does NOT cause AIDS.

    Are we supposed to risk the creation of millions of orphans in Africa because of the doubts of one Nobel laureate? What about all the other Nobel laureates? There are many of them, do we throw their opinions away because Kary Mullis is some kind of uber-Nobel prize winner? His expertise is not in the area of disease identification. That said, having read some of his points .. he has some validity but is well short of scientific proof that HIV does NOT cause AIDS. I have not read his opinions on the recent showing that those taking the newer AIDS treatments have shown marked improvement in their symptoms and immune cell levels.

    I recall a claim made by a Duesberg follower that a virus would be stupid to kill its own host (apparently smallpox didn't get that memo).

    It was probably not right of the scientific community to go after Duesberg the way he did, but on the same token Duesberg didnt have to become close minded to hold on to his theories.

    To answer your question about "Western Blot", the virus HIV has a defect in it's error correction mechanism and is unable to ensure that it is not creating proteins to which the body has antibodies to. This means that if say there are a million copies of the virus .. a few thousand may be invisible to the anti-body while thousands more are susceptible to it. That's one of the reasons why AIDS cant kill off a person rapidly.
  • by AndersOSU ( 873247 ) on Wednesday January 25, 2006 @10:01AM (#14556935)
    from the avert website:
    One line of argument can be based on animal experiments.43 In some studies, chimpanzees deliberately infected with HIV-1 have gone on to develop AIDS-like conditions (though this appears to be rare),44 while HIV-2 has had the same effect on baboons.45 Macaque monkeys have developed AIDS after being infected with a hybrid virus called SHIV, which contains genes taken from HIV.46 And in mice engineered to have a human immune system, HIV produces the same patterns of disease as in humans.47

    sources:
    #43 "Evidence from Animal and Laboratory Models", NIH, 1995
    #44 "Progressive infection in a subset of HIV-1-positive chimpanzees", O'Neil et al, J Infect Dis 182(4), October 2000
    #45 "Human immunodeficiency virus-2 infection in baboons is an animal model for human immunodeficiency virus pathogenesis in humans", Locher et al, Arch Pathol Lab Med 122(6), June 1998
    #46 "Chimeric simian/human immunodeficiency virus that causes progressive loss of CD4+ T cells and AIDS in pig-tailed macaques", Joag et al, J Virol 70(5), May 1996
    #47 "The SCID-hu mouse as a model for HIV-1 infection", Nature 363(6431), June 1993
  • by Mutatis Mutandis ( 921530 ) on Wednesday January 25, 2006 @01:09PM (#14559121)

    On the Western blot test: The virus has parts that can be allowed to be highly variable without seriously affecting its activity, and parts that need to be conserved because otherwise it would be deficient and longer replicate. On an intact, infective virus the parts exposed to the outer world tend to be highly variable ones, while the conserved ones are kept buried inside.

    Immunological tests are done on viruses that are broken up and no longer infective: Not only is this safer, but it allows the individual proteins to bind to their target sites, which is obviously impossible if they are bundled together in the virus. Nevertheless, the designers of the tests do have to take into account the variability of the virus, and AFAIK HIV testing kits are specific for regions.

    There is not a shred of a rational reason to doubt that HIV causes AIDS, as it has been very convincingly demonstrated that inhibitors of HIV enzymes delay progression to AIDS and can suppress the disease symptions. That the early tests on AZT were not so convincing is irrelevant; we now know that if patients are given only AZT, the virus will become resistant to it in a matter of weeks.

    That other viruses can also suppress the immune system is not surprising -- such a capability is obviously beneficial to a virus and would evolve naturally. HIV has an substantial and little understood arsenal of immune-suppressing tricks. And BTW immuno-deficiency this is by no means its only harmful effect, it also causes damage to the nervous system and the brain, in ways yet unclear.

    As for the idea that HIV may have evolved from a less dangerous human virus: This is not impossible in theory, but there is strong evidence that HIV originates from SIV, and no evidence for another origin. Also, the co-evolution of a virus with its host tends to make it less and not more harmful to the host; this is the trend that was observed for syphilis and has recently been reported for HIV as well. It is not in the interest of a disease to kill its host.

  • by nobody69 ( 116149 ) on Wednesday January 25, 2006 @03:13PM (#14560721)
    Actually HIV is detected in EVERYONE with AIDS. This is because by definition
    you have AIDS if HIV is detected in your system.
     
     
    Ahem, no. If you have Human Immunodefiency Virus antibodies in your system you are diagnosed as HIV-positive. If you are HIV-positive, and your immune system is giving up the ghost because the t-cells are being killed off by the HIV, you are diagnosed as having AIDS.
     
      If you're dying from an immuno-deficiency and HIV is not detected, you are diagnosed as not having AIDS!
     
     
    There are other ways to become immuno-deficient that are not due to HIV. Frex, you could have a genetic condition such as SCID (Severe Combined Immuno-Deficiency), radiation exposure leading to ARS (Acute Radiation Syndrome), or even immunodeficiencies resulting from chemotherapy.
  • by cweber ( 34166 ) <.cwebersd. .at. .gmail.com.> on Wednesday January 25, 2006 @04:04PM (#14561244)
    [While I am not into HIV virus research, I am a Ph.D. level structural biologist and feel qualified to answer this.]
    Won't work, unfortunately. Remember that a virus is an inanimate object composed of self-assembling parts. You can shake them apart all you want, they'll just reassemble. Unless you find a way to permanently damage the individual protein and nucleic acid subunits. However, I'm guessing the collateral damage to human tissue would be very high.
  • by smellsofbikes ( 890263 ) on Wednesday January 25, 2006 @04:36PM (#14561543) Journal
    I'm neither a PhD nor an engineer.
    Specificity is a big problem. There are roughly 40,000 proteins in the human proteome; an average protein is roughly 450 amino acids, the average amino acid contains about 20 covalent bonds, so the proteome alone has roughly 400M different covalent bonds in it. I submit that no matter how specific a frequency you can tune, it will vanish into the overlap from other proteins. Absorption bands are pretty broad. I'm assuming you'd focus on proteins, coz we can rebuild those; there are many less RNA macromolecules so there will be less overlap (although I still think it'd be far, far too broad an absorption spectrum) but if you screw up there you'll be destroying things that are much more difficult for the cell to rebuild: tRNA is an example of a serious problem since if you don't have any, you can't make any.
    I've built ultrasound transducers and know a bit about their design. It's really difficult to get even relatively narrow bandwidth on the designs I've seen, when you're talking about the required specificity. Within 0.5% of a given frequency, sure, but within 0.00005%? When you're trying to wipe out just one protein or just one RNA, that's the kind of notch you'd need to hit, I suspect.

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