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Medical Forum / Diseases and Disorders / AIDS / February 2005Information Theory and "HIV"
I have been mulling the following question over for a long time in hopes that someone more qualified than I would eventually take it up. AFAICT, no-one has, so here how it is: I am told that the number of codons that the genome of the hypothesized Human Immunodeficiency Virus is supposed to contain is quite small in comparison with the number of codons that the genome of the measles virus contains. And, as most of us know, the human immune system figures out how to beat back a measles infection after a couple of weeks, leaving the erstwhile patient "immune to measles" ever after. Therefore, isn't asserting the possibility that some miserable little vesicle which (lacking even a respectable protein coat of its own) scarcely deserves to be called a virus could possibly emerge after the 100s of millions of years of evolution that went into the "design" of the mammalian immune system, and proceed to do what none of its much smarter cousins can do -- namely, sneak in right under the noses of the very antibodies which, by a circular argument, are cited as the "smoking gun" that proves it exists -- a bit like asserting the possibility that a bank deposit vault (manufactured, say, by a reputable company which has been in the business for 100 years) that cannot be opened without making a particular sequence of 20 "turns" of its combination lock, each to a different one out of 100 numbered marks, might also -- because of some subtle error in its design -- be opened just by using a particular "magic combination" consisting, say, of only 4 turns? In short, isn't so-called HIV impossible on purely information-theoretic terms? -- First rate post. You make a point that I have not heard before and that seems to make sense. For my limited understanding, your conclusion seems to be supported by expert opinion on this complex topic. I assume you have read Grantham's Genome Hypothesis and based your theory, in part, on it's conclusions. http://post.queensu.ca/~forsdyke/granth01.htm > First rate post. You make a point that I have not heard before and that > seems to make sense. [quoted text clipped - 6 lines] > > http://post.queensu.ca/~forsdyke/granth01.htm Actually I hadn't, but I will now. Thank you for pointing it out to me. (latecomer) -- >I am told that the number of codons that the genome of the >hypothesized Human Immunodeficiency Virus is supposed to contain >is quite small in comparison with the number of codons that the >genome of the measles virus contains. Viruses come in various sizes and shapes, some with an envelope, some without. Some with many genes, some fewer. >And, as most of us know, the human immune system figures out >how to beat back a measles infection after a couple of weeks, >leaving the erstwhile patient "immune to measles" ever after. Measles is but one virus. And it can kill children. It is a linear (-) sense ssRNA, nonsegmented, enveloped and helical. Adenoviruses are linear with double stranded DNA, cubic, naked. The rest of your screed indicates you don't really give a damn about an intelligent conversation. In the event you are really interested, there are a number of excellent texts on virology that could clarify your questions. George M. Carter > ... there are a number of excellent texts on virology that could clarify > your questions. > > George M. Carter Thank you. Do any of the excellent texts in virology that you have in mind deal specifically with the issue I raised, namely, the question of how it can be possible that the human immune system, which can effectively neutralize a large variety of viruses much more complex than "HIV" is supposed to be, is unable to stop "HIV"? (latecomer) > Do any of the excellent texts in virology that you have in mind > deal specifically with the issue I raised, namely, the question of how [quoted text clipped - 5 lines] > > (latecomer) That is a bit like asking how the USA military can defeat an army but can't prevent a spy from operating. Or like asking why Saccharomyces cerevisiae is not harmful to most humans, but Salmonella typhi is. The number of genes in an organisms genome has very little to do with its pathogenic potential. In fact, many pathogenic bacteria have fewer genes in their genomes than their most closely related non-pathogenic relatives. >That is a bit like asking how the USA military can defeat an army but >can't prevent a spy from operating. Or like asking why Saccharomyces [quoted text clipped - 4 lines] >genes in their genomes than their most closely related non-pathogenic >relatives. Nicely put. Thanks. To answer his question, yes some of the texts touch on the topic of "pathogenesis" which is the discipline of delving into how an infectious agent causes disease. It is indeed an important area of investigation and in terms of HIV specifically, there is a growing and diverse body of evidence to clarify from the moment of infection to the moment of death the processes that occur in various cells, tissues and organs. Is the story complete? No! Nor is it for any disease. But the more we learn, the more interventions and therapeutic implications arise from this deeper understanding that can guide the way to better, safer and more effective therapies. George M. Carter > The number of genes in an organisms genome has very little to do with > its pathogenic potential. In fact, many pathogenic bacteria have fewer > genes in their genomes than their most closely related non-pathogenic > relatives. I am talking about the so-called Human Immunodeficiency Virus, not about bacteria. And I am talking about the relation between the maximum amount of information (instructions, if you will) that can be encoded by the genome of a virus and its /structural/ complexity, not about its 'pathogenic potential' per se. -- >> The number of genes in an organisms genome has very little to do with >> its pathogenic potential. In fact, many pathogenic bacteria have fewer [quoted text clipped - 3 lines] > I am talking about the so-called Human Immunodeficiency Virus, >not about bacteria. Actually, I think you have very little clue what you're talking about. > And I am talking about the relation between the maximum amount >of information (instructions, if you will) that can be >encoded by the genome of a virus and its /structural/ >complexity, not about its 'pathogenic potential' per se. And I KNOW I have no idea what you're talking about here. Do you know anything at all about the way genes express and the pathways to viral production? George M. Carter Nothing like a little bit of knowledge... Measles is the least effective virus I know of, in terms of survival - enveloped, RNA, negative stranded, single host, life-long immunity, no antigenic variation, no persistence... In isolated populations of under 100,000 it simply dies out. HIV on the other hand is a retrovirus, which means by definition it can evade the immune system by going latent AND persist as a provirus for as long as the cell lives. On the rare occasions that measles does something similar it too can cause disease despite immunity (subacute sclerosing panencephalitis for example). HIV is also extremely tolerant of mutations, whereas measles is not (perhaps the only virus mentioned in the same breath as HIV in terms of mutation rate is influenza). HIV has similar structural problems as measles (RNA, enveloped) but more than makes up for it elsewhere. The HIV genome is around 9,700 bases, measles is 15,900. Not all that different. Hepatitis B is only 3,200 and is far better than measles at surviving the host immune response! CMV has a genome of 230,000. Basically genome size doesn't mean much at all when it comes to viruses - that what was attracted me to studying them in the first place. Some of them get by with only three genes. The immune system DOES beat back HIV. If it didn't you'd run out of CD4 T cells after a month or so, instead of taking 8-10 years to get there! The problem is that measles cannot hide and cannot change. It _does_ try to suppress the immune system, but doesn't do enough obviously to persist. HIV is extremely smart, measles is stupid, in terms of viruses. You've got it entirely backwards. HIV is entirely possible, but you need to know enough information in order to come to that conclusion ;-) Field's virology devotes two chapters to HIV - one for the biology of the virus, one for the disease. It more than explains how HIV can cause AIDS, but I recommend getting a bachelors in biology at least prior to dipping into it. It is however extremely well written, so maybe that's not necessary. It's bloody expensive though. HIV is not alone in getting away from the immune system: herpes, varicella, Hep B, Hep C, CMV, EBV, pox. Some of these are more clever than HIV, far more subtle. Pox viruses have a veritable arsenel of immune-evasion genes, and can still be infectious even after loosing two of their three viral membranes (!) and sitting in the ground for a decade or more. HIV is good, but it's still a bit of an amateur compared to some other viruses. On the other hand, I use measles as my "what not to do when you're a virus" example. Cheers Bennett > HIV ... is a retrovirus, which means ***by definition*** it can > evade the immune system by going latent AND persist as a provirus for > as long as the cell lives. [my emphasis] If it exists. How can your HIV "evade the immune system by going latent" without getting its RNA *into* the cell in the first place? That is the part of the story that mystifies me. Or was it there already? How do you know for sure that the sections of human DNA which you claim to be HIV "provirus" are not present in all human beings? Has intact "HIV" ever been extracted from human semen, injected into uninfected human tissue culture, harvested, and this second generation then injected into a second uninfected human tissue culture, harvested, and then shown to be genotypically identical to the first? > The HIV genome is around 9,700 bases, measles is 15,900. Not all that > different. If it exists. Can you supply me with the URL of an electron microphotograph of an intact HIV /in vitro/, or a reconstruction of HIV based in Xray crystallography? I have not been able to find either. -- Getting the RNA into the cell is easy - the cellular immune response won't affect that at all, and the antibodies aren't going to be 100% efficient. Most of the progression risk is due to viral load, which is due to proviral load, which is established before the immune response even occurs. It's easy to know that HIV isn't endogenous - look for it! This has been done and HIV is only found in cells from people with anti-HIV antibodies (HIV infected). It's even only found in a minority of cells even in infected people, so clearly it can't be endogenous. I don't think your exact experiement has been done. HIV has certainly been cultured from semen (e.g. Dulious et al J Reprod Immunol. 1998 Dec;41(1-2):27-40. "Detection of HIV-1 in seminal plasma and seminal cells of HIV-1 seropositive men.") and sequenced (Zhu et al J Virol. 1996 May;70(5):3098-107. "Genetic characterization of human immunodeficiency virus type 1 in blood and genital secretions: evidence for viral compartmentalization and selection during sexual transmission.") HIV EM's are available in Briggs et al EMBO J. 2003 Apr 1;22(7):1707-15. "Structural organization of authentic, mature HIV-1 virions and cores.", Shehu-Xhilaga et al J Virol. 2002 May;76(9):4331-40. "The conformation of the mature dimeric human immunodeficiency virus type 1 RNA genome requires packaging of pol protein.", Richieri et al Vaccine. 1998 Jan-Feb;16(2-3):119-29. "Characterization of highly purified, inactivated HIV-1 particles isolated by anion exchange chromatography." and others. Some have even got EM's of HIV virions from in vivo biopsies (e.g. Pantaleo et al Nature. 1993 Mar 25;362(6418):355-8. "HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease." X-ray crystallography isn't possible for an entire virion I think, but EM's can certainly be used to get structural data, and it was the X-ray crystalisation of the protease that helped with the development of protease inhibitors. The Briggs paper did some structural analysis and a very recent paper has also apparently got some excellent data (cannot confirm cos I don't have fulltext access right now: Benjamin et al J Mol Biol. 2005 Feb 18;346(2):577-88. Epub 2004 Dec 19. "Three-dimensional Structure of HIV-1 Virus-like Particles by Electron Cryotomography." A similar experiment was performed by Zhu et al Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15812-7. "Electron tomography analysis of envelope glycoprotein trimers on HIV and simian immunodeficiency virus virions." Available URLs are: http://embojournal.npgjournals.com/cgi/content/full/22/7/1707 http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=11932399 http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v362/n6418/full/ 362355a0.html&filetype=pdf http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=14668432 Cheers Bennett > It's easy to know that HIV isn't endogenous - look for it! Exactly. Outside the cell. > Available URLs are: > http://embojournal.npgjournals.com/cgi/content/full/22/7/1707 > http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=11932399 > http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v362/n6418/full/ 362355a0.html&filetype=pdf > http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=14668432 Thank you very much indeed. At least at first glance, the first of these "The Structural organization of authentic, mature HIV-1 virions and cores" would seem to be ideal for my purposes. It will probably take me a couple of weeks to figure out what it says. -- Skeptic - Endogenous viruses might still produce virus-like particles. The real test is to look for it _inside_ the cell, using DNA techniques. This has been done for HIV, and it ain't there. The Briggs paper has it's own flaws, but does have nice pictures! :o) Cheers Bennett > Nothing like a little bit of knowledge... > > Measles is the least effective virus I know of, in terms of survival - > enveloped, RNA, negative stranded, single host, life-long immunity, no > antigenic variation, no persistence... In isolated populations of > under 100,000 it simply dies out. But those are all after the fact observations. The question posed was very simple (and of course escaped GM Carter too): How can such a simple organisms do so many (complex) things? - Escape annihilation by the immune system... - Lie dormant for 8 years or more while also... - Mutate like a maniac (with only 9 genes to work with) - Avoid causing immunity in the host, in fact, creating nothing but new strains that are supposed to make stopping a lifelong course of ARV's a hazardous business for the patient and mankind... Did I leave anything out? Alex Alex: After the fact observations are easy - the after the fact observations are that HIV infection leads to AIDS, if untreated, in around 95% of people. No need to explain that I guess. Escaping the immune system is relatively easy, especially if you're a retrovirus. Just integrate and you're done. It isn't dormant, it's constantly replicating. You know this because it mutates ;-) It uses two non-error-correcting enzymes as part of its replication strategy. It's no surprise it mutates rapidly, same as flu. You only need one gene to give rapid mutation rates. It does cause an immune response, but the response isn't enough to clear the infection. Those with stronger responses take longer to progress - some never do. It's not doing anything more complex than many other viruses do. Flu has 8 or 9 genes (depending on the species), Hep B has only 4 genes and one of them is a readthrough of another! It does a very similar job to HIV, in terms of long-term survival in the host. Number of genes do not necessarily correlate to "ability". You don't have a gene for immune evasion and a gene for immune suppression and a gene for mutation, it doesn't work like that. Hep B for example manages to evade the immune response by simply making a ton of envelope protein. The immune system is so busy cleaning up the mess it can't find the real virus particles - but you can't label the envelope gene an "immune evasion" gene, even though that's what it does. This is all toeing the party line as far as virology goes, HIV does nothing special. There is not a single aspect of HIV that you can't find in another virus, somewhere. The only unique thing about HIV is the combination. How does such a "simple" organism do so many (complex) things? Welcome to the world of virology :o) Cheers Bennett > The question posed was very simple (and of course escaped > GM Carter too): How can such a simple organisms do so many [quoted text clipped - 11 lines] > > Alex There has never been any correlation shown between the genetic complexity (number of genes) and a particular viruses ability to survive, infect, and do damage to those hosts it can infect. What part of that don't you understand Alex and Skeptic? Complexity as it relates to a particular virus effects on host organisms has less to do with the total genome of the virus then do the attributes of the genome and the strategies for survival those attributes create in the virus. So one can not nor should not judge the complexity of a virus simply by counting it's genes. One judges the complexity of a virus based on quantifying of it's survivability, infectivity, mutability, ability to adapt to different threats both immune based and drug based etc etc. Gary Stein >>The question posed was very simple (and of course escaped >>GM Carter too): How can such a simple organisms do so many [quoted text clipped - 15 lines] > (number of genes) and a particular viruses ability to survive, infect, and > do damage to those hosts it can infect. Let me put it to you this way: suppose for the sake of argument that the virus that is said to cause "AIDS" does not exist. What would force you to abandon that supposition? That is, with the benefit of hindsight, at exactly what point does it become logically necessary to postulate the existence of "HIV"? -- >>>The question posed was very simple (and of course escaped >>>GM Carter too): How can such a simple organisms do so many [quoted text clipped - 25 lines] > > -- When one discovered that group of patients who showed continuous and steady declines of there CD4 T-Cells all tested positive for HIV and one could accurately predicate the outcome of there disease progression based on Viral Load values. At that point one has no choice but to see that HIV is in deed the cause of AIDS. Gary Stein snip> >The question posed was very simple (and of course escaped >GM Carter too): How can such a simple organisms do so many >(complex) things? Thanks for clarifying. I'm so gosh darn dense sometimes. But you know, if you weren't such a disingenuous fellow wrapped up in your own set in concrete bullshit, you might discover that the question as framed above is REALLY elegant and leads to a whole slew of fascinating discoveries about our brief existence. You'd rather use the question like some rhetorical whipping post from dipshits like Ann Coulter rather than actually exploring it. George M. Carter |
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