POZ Community Forums
Meds, Mind, Body & Benefits => Research News & Studies => Topic started by: Inchlingblue on November 12, 2009, 12:59:16 pm
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Someday all this research is bound to lead to an actual cure. I mean, seriously, so much is known about this little bugger it's astounding. I would not be surprised if the cure is not already under our noses (this is something Martin Delaney has also said). Here's some of the latest findings on how HIV is assembled and released from infected cells, which was learned by using Total Internal Reflection Fluorescence Microscopy along with Wide-Field Fluorescence Microscopy.
Hoping for a fluorescent basket case
How HIV is assembled and released from infected cells
Although recent advances have raised hopes that a protective vaccine can be developed, acquired immunodeficiency syndrome (AIDS) remains a major public health problem. Much has been learned about HIV-1, the virus that causes the disease. However, basic aspects of person-to-person transmission and of the progressive intercellular infection that depletes the immune system of its vital T cells remain imperfectly understood. In a paper published today in the online journal PloS Pathogens, Professor Don Lamb's group at the Ludwig-Maximilians-Universitaet (LMU) in Munichs's Department of Chemistry and Biochemistry, together with colleagues in Heidelberg, describe in detail how new virus particles assemble at the membrane of infected cells, and are released to attack healthy cells nearby. The new findings could help provide clues as how to interrupt the process of intercellular viral spread. (PLoS Pathogens, 6 November 2009)
As many of us have learned from personal experience, computer viruses, which contain short pieces of malicious code and arrive in anonymous packages, can gum up data-processing routines. This definition also fits their biological counterparts, which generally comprise compact genomes packed in protein shells, and enter cells via specific portals. For example, the retrovirus HIV-1 has only nine genes in its RNA genome and infects cells by binding to specific receptors. Inside the cell, the genetic material is copied and 15 viral proteins are synthesized. They interact to pack the genomic RNA into new viral particles. These are then extruded from the cell, wrapped in an envelope of membrane bearing viral proteins that direct the parcel to the next susceptible cell.
The basket that encases the viral RNA is constructed from the Gag protein. Gag is highly versatile: It can bind to the inner face of the cell membrane, to the viral RNA, to itself (to form the shell around the RNA) and to cellular proteins that extrude the newly assembled particle into the extracellular medium. Indeed, Gag can form virus-like particles in the absence of other viral proteins. For their experiments, Professor Lamb's team used cultured cells containing eight of the HIV-1 genes, one of which coded for a fluorescent form of Gag.
"We adopted our custom-built microscope specifically for the experiment, visualizing Gag in the cellular plasma membrane by Total Internal Reflection Fluorescence Microscopy while alternately switching to Wide-Field Fluorescence Microscopy to get a deeper view into the cell", explains Lamb. This allowed the team to track single Gag particles and follow the assembly process, in real time.
Once virus assembly is switched on within an infected cell, the membrane surface of the cell becomes covered with viruses in one to two hours. Each virus is assembled individually at the plasma membrane on the time scale of minutes, rejecting the idea of a reusable assembly platform that is believed to exist for other viruses. By tracking individual viruses, the scientist could follow the processes of assembly from initiation of assembly through to release, learning that it takes about 25 minutes to produce an HIV virus. Hence, a lag of 15-20 minutes precedes release of the enveloped virus, presumably because it takes time for the hijacked cellular budding machinery to close of the virus and release it into to the extracellular medium.
"Using a 'photoconvertible' version of the famous green fluorescent protein – whose discovery and utilization in biological systems were honored with the Nobel prize in chemistry in 2008 – attached to the Gag protein, we were able to convert the color of membrane bound Gag proteins from green to red", says Lamb. "Thereby, we could determine that viruses were assembly from protein delivered directly from the cytosol or had only arrived recently to the plasma membrane." The new findings add an important dynamic dimension to the process of intercellular viral spread. If they help find ways to interrupt it, HIV-1 could finally be stamped as "undeliverable". (PH)
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Publication:
"Dynamics of HIV-1 assembly and release"
Sergey Ivanchenko, William J. Godinez, M. Lampe, H.G. Kräusslich, R. Eils, K. Rohr, C. Bräuchle, B. Müller, D.C. Lamb
PLoS Pathogens, 6 November 2009
Contact:
Professor Dr. Don C. Lamb
Department of Chemistry and Biochemistry
Excellence clusters "Nanosystems Initiative Munich" (NIM) and "Center for Integrated Protein Science Munich" (CiPSM) at LMU Munich
Tel.: +49 (0) 89 / 2180 - 77564
E-mail: Don.Lamb@cup.uni-muenchen.de
LINK:
http://www.eurekalert.org/pub_releases/2009-11/lm-hfa111209.php
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"I would not be surprised if the cure is not already under our noses (this is something Martin Delaney has also said). "
Inch,
We all await that "Eureka" moment. It will happen!
v
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I am sure there will be a cure very soon ..5 yrs -10yrs that's not a long time to wait, but lot of time for research to create wonders..
Thank you inch and veritas for keeping us all posted on the research front. I find your posts very knowledgeable.
Regards.
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excellent find...
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Quite fascinating. Thanks for sharing, Inc.
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Very interesting...thank you.
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Hey Livebythemoon, who are the members of the Trinity in your pic?
The middle one looks a little like Bjork but the pic is too small on my screen to be able to tell.
;)
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so so many findings i have noticed about the virus on almost a weekly basis here,and the old sentence is still widely :"its a mutating virus and hard to understand", "the findings will be studied and this could take many many years " ....etc !!!.
so many findings saved in files,not implemented and if so,we get distracted by the next new findings and forget about the first one and so on ... its going forever.
many scientists are just farting arround,sorry.
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so so many findings i have noticed about the virus on almost a weekly basis here,and the old sentence is still widely :"its a mutating virus and hard to understand", "the findings will be studied and this could take many many years " ....etc !!!.
so many findings saved in files,not implemented and if so,we get distracted by the next new findings and forget about the first one and so on ... its going forever.
many scientists are just farting arround,sorry.
You are totally right sensual, is the same story, every week, scientists found a different Achilles' heel of HIV
???
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Dear Friends,
For quite some time I've been thinking about the process of drug discovery, not only in relation to this SH*, but in general. I lost an aunt to colon cancer and was sad to see her suffering. Hope you understand my opinions and at the end we need to do something to influence. My idea is to write a document with examples of publicly funded research, promising discoveries that never reach clinical trials or die soon afterwards, despite having promising results, and propose changes to the medical research paradigm. The way I see this, the document would be a collaborative effort of the members of this forum, through a wiki or something similar that everybody could edit. I can only work on this during the Christmas brake. Please say what you think. I'll explain my ideas:
1) the bottleneck occurs after the discovery phase. The public and also private funding of basic research has made amazing progress. Maybe not alone, but combination of therapeutic vaccines (Geovax, Dermavir, Bionor, Virxsys, HIVcide, vaccine of Jean-Marie Andrieu (forums.poz.com/index.php?topic=29858.0), abzymes of Prof. Paul, gcmaf of Dr. Yamamoto, would be at least account for a functional cure. No more HAART or just one small molecule drug. Why has Geovax to struggle to find a place to do the clinical trials and why do they have to rely on a free donation from Formatech to make the vaccine? Why has Prof. Sundhir Paul to start a charity to raise money to move to clinical trials? Geovax is loosing more than one year to start the therapeutical trials and only God knows when will Prof Paul be able to start the human trials! The other question is whether Dr. Paul is the best person to run the trials! Is he also an expert in the subject? Don't think so!
2) What to do then? My view is that a kind of a patent pool should be brought to the basic research in particular when receiving public money. After the animal studies are completed, and the new product is ready for clinical trials, someone else either a private company or government labs working within the research network, should advance the project. Nothing would be lost and all progress could be reused later in different projects. For example, if someone was doing gene therapy trials, the vector used for gene delivery could be used later by another group.
3) How to lure the private sector into participating? For that I think the paper recently published by Prof. Jeffrey Harris (forums.poz.com/index.php?topic=29734.0) gives some clues. The way I understand the new paradigm of research, it would be beneficial for the government since because the prices of treatment would be much lower, the private sector ( I mean here the biotech companies such as Geovax, Nanoviricides, Virxsys) would have a much low risk but of course lower profits at the end. For example, even if VIR496 doesn't work as expected, the delivery vector probably does and could be reused later. At the end companies should always have the option to repay the government for the investment if they decide to go alone.
4) Are there any losers? In the first year or two yes: the big pharma that currently sell the small molecule drugs! But after the initial schock, again they can have a steady income. Not in the billions as it happens today, but in the millions. After all they are the only ones with the infrastructure to distribute the new treatments worldwide. Their revenues would be lower but their risk would be even lower.
5) What about the winners?!! After a few years (3 or 4) everybody would be winning: patients because of the new treatments, taxpayers because the money invested in basic/applied research would result not only in new treatments but in cheaper treatments, small biotech companies would have an easier life, their efforts would be rewarded and even if not entirely successful in one project they would be able to continue working in new ideas, and big pharma would continue to have significant incomes and wouldn't have to pay billions aquiring smaller companies with interesting portfolios.
These are the ideas I have in mind after we can put a decent document together we could have our voices heard. For me is a scandal with all the investments we do in research not having a continuation to better treatments. What do you think?
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so so many findings i have noticed about the virus on almost a weekly basis here,and the old sentence is still widely :"its a mutating virus and hard to understand", "the findings will be studied and this could take many many years " ....etc !!!.
so many findings saved in files,not implemented and if so,we get distracted by the next new findings and forget about the first one and so on ... its going forever.
many scientists are just farting arround,sorry.
The real problem is the immense time lost between the findings and the beginning of clinical trials. There's a lot of burocracy which doesn't allow a rapid process to test compounds on humans. All the preclinical phase and the following animal trials steels a lot of time.
We saw many times that animals respond very differently than humans reguarding the efficacy and safety of new compounds. Is animal testing really useful? Probably a big lobby of animal testing devices is behind all this to keep alive an industry. Please don't accuse me for conspiracy theorizing. Profit applies in the same way to research and drug development as it applies to the development and selling of cars. But this is another story and I don't want to go off topic.
Finally this new born company ViiV Healthcare which seems useful only for the shareholders of Pfizer and GSK. As we know big pharma doesn't invest in the cure. They push old compounds with a new lifting and package on the market claiming to be on your side in fighting the disease. But they are giving you nothing else than a clone of the old drugs they invented 15 years ago.
We need a different approach in the battle of HIV. Industrial competition is good but as long as big pharma dictates the rules we will not have a breakthrough.
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when i tested poz 9 years ago i heard the phrase : "in 10 years there will be a cure" am not saying a cure should be here in a year or so,nor am i optimistic when it comes to a cure soon anyways,but it makes me really ANGRY when i hear some high ranking researchers still use the 10 years time frame !!! . is this like the carrot and the donkey ? and why ?.
And all those promissing therapies under trials,trust me they will be closed at some stage,and you wont even dare to ask why.
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For me is a scandal with all the investments we do in research not having a continuation to better treatments. What do you think?
In an ideal world no profit should be made on life threatening conditions like HIV, cancer and others. Public money should be more than necessary to the research and development of new drugs and cures. The pharma industry is able to survive with Viagra and Prozac.
Also somebody should explain why big pharma is making money on something funded by private donations? Since the discovery of the virus billions of dollars went into research. Those fundings shouldn't be accessible to private companies but the money from taxes and donations goes into the pockets of the big companies. The entire political and economical system behind this is a mess.
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when i tested poz 9 years ago i heard the phrase : "in 10 years there will be a cure" am not saying a cure should be here in a year or so,nor am i optimistic when it comes to a cure soon anyways,but it makes me really ANGRY when i hear some high ranking researchers still use the 10 years time frame !!! . is this like the carrot and the donkey ? and why ?.
And all those promissing therapies under trials,trust me they will be closed at some stage,and you wont even dare to ask why.
Give people hope and the believe of a change and they will follow you. Every president adopts this strategy to win the elections and it is the same way the church, the industry and the corporations continues to sell you those dreams.
The issue is that after all the years we aren't able to understand how much they're fooling us.
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Hey Livebythemoon, who are the members of the Trinity in your pic?
The middle one looks a little like Bjork but the pic is too small on my screen to be able to tell.
;)
Inchlingblue, the trinity are (from L-R) PJ Harvey, Björk, and Tori Amos :) I attached a larger version of a similar pic (sorry if this is a hijack of some sort).
People, why must we turn every post made in the Research News and Studies into a whine party?
[attachment deleted by admin]
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You mean you expected a new comment from them? "Predictable" is the word...
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You mean you expected a new comment from them? "Predictable" is the word...
I know, how foolish of me. I was gone for about 3 weeks and expected them to change. In those same 3 weeks they expected "The Cure" (and I don't mean the band) to pop out of the woodwork.
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But they are giving you nothing else than a clone of the old drugs they invented 15 years ago.
You are wrong, they invented NNRT NRT and IP at least 20 years ago, they started to sell these drugs in 1995/1996 after humans clinical trials. Raltegravir has been invented 15 years ago.
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strange those who say we are whining,just because we think otherwise,and as if they are only right.
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strange those who say we are whining,just because we think otherwise,and as if they are only right.
Then why are you regularly on the Research News board if all you do it act petulant because they didn't create a cure in the last 24 hours? If you believe this is a big conspiracy or that we'll never have a cure why don't you save yourself the time of visiting these boards and rehashing your same old complaints? You're not contributing anything new or interesting. Sorry if you think you are.
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People, why must we turn every post made in the Research News and Studies into a whine party?
Same kids, same sandbox. Do I really need to point that out?
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lol sounds like some of the pharma sharholders are upset
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lol sounds like some of the pharma sharholders are upset
wow, it must have taken you a long time to think up that response. good work.
but you didn't answer my question: why do you visit the Research boards? enquiring minds want to know ;)