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Author Topic: Proteins that are used to halt HIV are identified.  (Read 5655 times)

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Offline Dachshund

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Proteins that are used to halt HIV are identified.
« on: January 11, 2008, 08:41:39 AM »

http://www.washingtonpost.com/wp-dyn/content/article/2008/01/10/AR2008011003548.html?hpid=moreheadlines


A research team announced yesterday that it has identified about 270 human proteins that the AIDS virus apparently needs to infect a person, instantly providing researchers with dozens of new strategies for blocking or aborting HIV infection.
« Last Edit: January 11, 2008, 08:43:12 AM by Dachshund »

Offline mjmel

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Re: Proteins that are used to halt HIV are identified.
« Reply #1 on: January 11, 2008, 08:56:01 AM »
glycosylation? wow, armed with this new knowledge.........

Mike M

Offline powerpuff

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Re: Proteins that are used to halt HIV are identified.
« Reply #2 on: January 11, 2008, 06:10:38 PM »
interesting, however it doesn't mention reaching latent cells?? :-\ could this cure or just be another target for drugs?

Offline J220

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Re: Proteins that are used to halt HIV are identified.
« Reply #3 on: January 11, 2008, 10:52:26 PM »
interesting, however it doesn't mention reaching latent cells?? :-\ could this cure or just be another target for drugs?

Impossible to say at this time, I surmise. But given that this is new and truly groundbreaking, I would not be surprised that they can pinpoint some protein without which an infected cell cannot survive.
"Hope is my philosophy
Just needs days in which to be
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Offline bimazek

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Re: Proteins that are used to halt HIV are identified.
« Reply #4 on: January 11, 2008, 10:52:26 PM »
dont worry about the latent cells because if these discoveries lead to new meds that work it will stop the replication of all hiv particles and make latent cells unimportant
long term non progressors have no disease progression and they have latent reservoirs remember
and this is part of the discovery, one of those 273 genes 273 proteins is one they found is mutated in
long term non progressors so this means that
this group has latent reservoirs but the hiv does not come out because of this gene and protein
thus
a group who have a latent reservior but do not have any disease progression exists-- long term non progressors-- and why this is has been found
i will post this on here all very good info
This is a double whammy good breakthru
two big breakthroughs
or 273  breakthroughs plus 1 super huge one  and that one is incalculably huge...
breakthrough one...
basically they found 273 new ways to possibly attack HIV
breakthrough two  ...
and at least one of the genes is so important in fact it is the way that nature evolved a gene that is not susceptible to hiv, shared in common by all the famous long term non progressors ...

rare individuals who do not progress to AIDS when they become infected with HIV.  so this is especially cool because it should be possible  to find a molecule-- a medicine that shuts off this gene that produces a protein that HIV loves and needs and we  also know that this one this gene/protein in particular is not very important not very necessary for human life because ALL long term non progressors have a mutation that removes this  gene and removes this protein and they live just fine without problems
i should say they have a mutation that suppresses or squelches this gene and this protein
and these humans don't seem to need that gene or that protein very much at all
They found the gene and protein involved with that...
the famous long term non progressors ...
http://www.webmd.com/hiv-aids/news/20080110/273-new-possible-targets-for-hiv-drugs?page=2
remember harvard was the site where they were studying long term non progressors from all over USA to find the genetic similarities

Experts Say Finding Is Major Advance continued...

One hopeful finding is that some people carry a mutant version of one of the proteins identified by the Elledge team, apparently with no harmful consequences. This mutant version of the protein, Haynes and colleagues recently learned, is found in some of the rare individuals who do not progress to AIDS when they become infected with HIV.  "One of the critical challenges of HIV research is to learn as much about the virus as we can, as fast as possible," Haynes tells WebMD. "Studies like this have the potential to move our knowledge forward quickly, which is important given the growing worldwide epidemic of HIV and AIDS."  The findings have broad significant beyond AIDS research. They show that the same techniques can be used to dissect the workings of other viruses -- and of cancers. Elledge says his team is now looking for the Achilles' heels of cancer cells.
Elledge and colleagues report their findings in the Jan. 10 issue of the online journal Science Express.

http://news.google.com/nwshp?hl=en&tab=wn&ncl=1126137345&topic=m
..........................
along with the many new things coming out i think this is one is the one final nail, albeit 5-9 years away from now to reach the market that will give many many many if not a vast majority a long long life. the reason also is that these genes are necessary in many other viral diseases and now science knows that for Hepatitis and many other diseases these genes must be looked at so there will be many reasons to invest....

this is the best news i have read as far as basic research in the 20 months i have been poz
there have been other great best news that are brand new approved drugs and as poz mag or another mag said in this issue 2007 is as big a break thru year as 1996 for hiv drugs
but for  basic research this is huge breakthru
my hats off to the smart and diligent scientists (i am a little shocked that this had not been done before but really it has only been 7 to 11 years that DNA RNA and human genome's sequencing existed and also the big big thing and reason why it happened now is it is only in last 1 or 2 or 3 that the cost of doing DNA RNA and human genome's sequencing fell from like five hundred million to one hundred thousand.
go it is basically happening at the right time it really could not have happened earlier
i mean geeze they had to do the DNA human genome's sequence first which they just finished a couple years ago before they could go back thru trial and error and test every gene again in a test tube one at a time to see if the proteins the gene make helped hiv grow fast.
anyway
hugs to everyone

this is a huge step forward
esp. the discovery for a gene (is it one or more than one) for non term non progressors
this is a nobel prize if you ask me
or should be.
http://news.google.com/nwshp?hl=en&tab=wn&ncl=1126137345

HIV Research Opens Up Potential Targets for Drugs
New York Times, United States - 7 hours ago
By DONALD G. McNEIL Jr. Using a new type of genetic screen, researchers at Harvard Medical School have identified 273 proteins that the AIDS virus needs to ...
"This is likely destined to be one of the best papers on HIV for this coming decade," said Robert C. Gallo, co-discoverer of the AIDS virus, who was not involved in the study. "I think it is terrific."  Gallo, who is director of the Institute of Human Virology in Baltimore, called the Harvard research "simply an elegant combination of modern molecular biology, new technology and bioinformatics that was used in a manner that has truly led somewhere."    Fauci, whose National Institutes of Health-affiliated laboratory also studies HIV's interaction with cells, said he is impressed by the strategy of selectively inhibiting cellular processes and then watching to see the effects.  "There is nothing that is completely new under the sun, but that is relatively [new]..." he said.
Fauci always is understated when others make the discovery not himself.

« Last Edit: January 12, 2008, 08:40:52 PM by bimazek »

Offline J.R.E.

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Re: Proteins that are used to halt HIV are identified.
« Reply #5 on: January 12, 2008, 02:46:58 AM »


Here's  another related article :


http://www.medicalnewstoday.com/articles/93739.php



Ray
Current Meds ; Viramune, Epzicom, 40mg of simvastatin, 12.5mg of Hydrochlorothiazide.
Metoprolol tartrate 25mg



http://forums.poz.com/index.php?topic=40802.0

http://forums.poz.com/index.php?topic=45159.0

http://forums.poz.com/index.php?topic=39722.msg495621;topicseen#msg495621

http://forums.poz.com/index.php?topic=46806.0

http://forums.poz.com/index.php?topic=39414.msg491701#msg491701


 In October of 2003, My t-cell count was 16, Viral load was over 500,000, Percentage at that time was 5%. I started my first  HAART regimen  on October 24th,03.

 As of 6/4/14,  t-cells are at 423, Viral load <40

 Current % is at 13% 

  
 62 years young.

Offline powerpuff

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Re: Proteins that are used to halt HIV are identified.
« Reply #6 on: January 12, 2008, 02:47:32 PM »
So when would this available? it is not persay a drug but they would have to make drugs that would work with theses proteins? that could take years right???
so from what I understand these proteins could block replication. this is no cure. but would make one a long progressor??/??? am i right bim

Offline powerpuff

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Re: Proteins that are used to halt HIV are identified.
« Reply #7 on: January 12, 2008, 03:03:34 PM »
so one would have to take drugs for life that block this protein that would make one a long term progressor? what would make this any different than any other drug, other drugs slow down the replication but eventually the immune system fights and gives out. this would block hiv but stop it completely. finding these proteins and genes are great ,devising a method or drug that will immitate a natural slow progressor sounds tricky? i am hopeful but skeptical

Offline powerpuff

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Re: Proteins that are used to halt HIV are identified.
« Reply #8 on: January 12, 2008, 03:13:03 PM »
could blocking these proteins be dangerous? in the halting of hiv/? there might be consequences??

Offline MOONLIGHT1114

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Re: Proteins that are used to halt HIV are identified.
« Reply #9 on: January 12, 2008, 04:32:25 PM »
We discussed this at my support group last night, it sounds very promising as far as leading to the development of new meds!

273 proteins, wow!

~ Cindy
HIV+ since '93, 1/12 - CD4 785 and undet.   WOO-HOO!!

Offline bimazek

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Re: Proteins that are used to halt HIV are identified.
« Reply #10 on: January 12, 2008, 07:45:40 PM »
I read every news article found by google, hundreds, to find these gems in the report, I also followed the clues and researched what all these new discoveries are and then found definitions of the functions of these genes, some of it is a bit heavy in the science but worth knowing, my big question, if anyone has access to the full article is what is the gene that all long term non progressors share in common...

 They used human genome data to create a panel of over 21,000 host genes, and found that targeting nearly 400 of those managed to reduce HIV infection without killing the cell. Further validation reduced the final number of genes of interest to 273. Most of these blocked either infection or the initial production of new HIV RNA; once HIV proteins appeared on the cell surface, only 28 genes, when blocked, could prevent the formation of functional viruses.   These genes are involved in a large variety of processes, highlighting HIV's dependence upon its host. The list includes parts of the nuclear pore, RNA transcription machinery, Golgi complex, and factors that control the persistence and modification state of proteins on the cell surface. http://arstechnica.com/journals/science.ars/2008/01/11/massive-screen-uncovers-hivs-cellular-partners

Elledge said, "We're closing in on a systems level understanding of HIV, which opens new therapeutic avenues."
"We might be able to tweak various parts of the system to disrupt viral propagation without making our own cells sick," he explained.   http://www.medicalnewstoday.com/articles/93668.php

http://www.sciencemag.org/cgi/content/abstract/1152725
identified 273 HIV-dependency factors (HDFs). These proteins participate in a broad array of cellular functions and implicate new pathways in the viral life cycle.   Further analysis revealed previously unknown roles for retrograde Golgi transport proteins (Rab6 and Vps53) in viral entry, a karyopherin (TNPO3) in viral integration, and the Mediator complex (Med28) in viral transcription.

Basically looks like these are some of the big targets for future medicines...
if someone has access to the actual paper my big question is what gene/protein did they discover specifically that all long term non progressors have in common.  basically what this discovery says is the simple story about the entry, integration, reverse transcriptase and budding etc is a very over simplified life cycle of hiv and there are perhaps 273 steps involving many genes. 

Here are the four main areas of the discovery...

retrograde Golgi transport proteins (Rab6 and Vps53)
viral entry
karyopherin (TNPO3) in viral integration
Mediator complex (Med28) in viral transcription.

Rab6
Protein transport. Regulator of membrane traffic from the Golgi apparatus towards the endoplasmic reticulum (ER)   regulates protein transport at a step between dense granules and the late Golgi cisternae and that overstimulation or inhibition of Rab6 function partially blocks constitutive secretion of proteins by disregulating their transport to dense granules. The effect of Rab6 overstimulation appears to enhance the brefeldin A-induced resorption of constitutively secreted cargo and Golgi cisternae  Belongs to the small GTPase superfamily. Rab family  http://www.wikiproteins.org

Vps53 
(vacuolar protein sorting 53 homolog
VPS53 (vacuolar protein sorting 53 homolog  Involved in retrograde transport from early and late endosomes to late Golgi by linking the vesicle through the t-SNARE TGL1 to the Golgi, leading to the membrane fusion between late Golgi and endosomal vesicles     Component of the GARP (Golgi-associated retrograde protein) complex, Vps51p-Vps52p-Vps53p-Vps54p, which is required for the recycling of proteins from endosomes to the late Golgi; required for vacu... 
http://www.genecards.org/cgi-bin/carddisp.pl?gene=VPS53

TNPO3 
Transportin-3 (Homo sapiens)   Seems to function in nuclear protein import as nuclear transport receptor. In vitro, mediates the nuclear import of splicing factor SR proteins SFRS1 and SFRS2, by recognizing phosphorylated RS domains

Med28
Mediator of RNA polymerase II transcription subunit 28 (musculus)   organism specific gene   Component of the mediator complex, a complex that can either repress or activate transcription. Mediator complexes are essential for basal and regulated expression of nearly all RNA polymerase II-dependent genes. They may act as a bridge, conveying regulatory information from enhancers and other control elements to the promoter. May be part of a complex containing NF2/Merlin that participates in cellular signaling to the actin cytoskeleton downstream of tyrosine kinase signaling pathways (By Similarity)http://www.wikiproteins.org

Offline Miss Philicia

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Re: Proteins that are used to halt HIV are identified.
« Reply #11 on: January 12, 2008, 07:59:42 PM »
could blocking these proteins be dangerous? in the halting of hiv/? there might be consequences??

No offense, dear -- but aren't you supposed to limit your posts to the Am I Infected section according to this warning by Tim Horn?  As it is you just posted 3 simultaneous posts in this thread in less than 30 minutes.  I'd hate to see you start up that obsessive habit again.
"Iíve slept with enough men to know that Iím not gay"

Offline Patrick

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Re: Proteins that are used to halt HIV are identified.
« Reply #12 on: January 13, 2008, 02:54:29 PM »
I think this is very good news.  The more ways researchers and scientists can find to fight this disease, the better off we all are.  Perhaps some of these proteins will prove necessary for the survival of HIV in the reservoir sites in our bodies, and that by blocking them we can truly find a cure.

Short of that, this most certainly opens the door to new and better drugs.  Yeah, that likely means we'd all still have to take medicine daily, but the more drugs that are out there, the better our options will be regarding drug efficacy, side-effects, and viral resistance/mutation.  If a drug that blocks certain proteins can be found that wouldnt' allow HIV to mutate around it while being relatively non-toxic, then we'd all be able to live pretty normal lives. 

Sounds a bit optimistic, I know, but look how far the drugs have come from 10 years ago.  10 years from now, a plethora of drugs based directly on this research could be on the market, allowing all of us the chance at side-effect free, long lives.  That sounds pretty good to me.   The key is for all of us here to take care of ourselves and live long enough to see this happen.  That is my plan.
Seroconversion - late October 07
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Offline bimazek

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Re: Proteins that are used to halt HIV are identified.
« Reply #13 on: January 13, 2008, 06:38:54 PM »
one more point is one final important discovery of this paper

ZNRD1 gene discovered by this study at Harvard this week and also confirms a Duke Univ separate study

ZNRD1 gene associated with slower progression, ZNRD1 codes a protein

my question
Which gene/protein did you find that long term non-progressors seem to
have a mutated version of that does not allow HIV to replicate?
 
The Duke University group recently published that polymorphisms in the regulatory regions
of the ZNRD1 gene were associated with
slower progression to disease in patients living with HIV. The particular
polymorphisms in ZNRD1 that were protective
resulted in higher levels of the protein. We, at Harvard, also found ZNRD1 in our screen, but
in this case, lower levels of ZNRD1 inhibited viral infection.
ZNRD1 is associated with RNA polymerase one, which transcribes the ribosomal
genes in the nucleoli.   Why HIV is inhibited when ZNRD1 levels are lowered with siRNAs in tissue culture
cells remains for us to figure out. Also what if any connection this has to the
slower progression to disease in patients with the protective polymorphisms also
remains to be figured out. However, the fact that this gene came up in both
studies makes  it an interesting candidate for future study.
 
http://www.medicalnewstoday.com/articles/77630.php

Variations in three genes might help people newly diagnosed with HIV control their viral loads, according to a study published Thursday in the online edition of the journal Science, the San Francisco Chronicle reports. For the study, a group of international researchers from the Center for HIV/AIDS Vaccine Immunology, led by David Goldstein of Duke University, pooled information about 486 HIV-positive people from a group of 30,000 to determine if genetic variations are linked to the disease, the Chronicle reports.

http://209.85.173.104/search?q=cache:4nW3GpDVK0MJ:cfar.duke.edu/wysiwyg/downloads/Fellay_PowerPoint.pdf+ZNRD1+hiv&hl=en&ct=clnk&cd=4&gl=us

http://abouthivaids.blogspot.com/

Offline powerpuff

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Re: Proteins that are used to halt HIV are identified.
« Reply #14 on: January 14, 2008, 08:19:44 PM »
virip peptide inhibiter natural protein in blood is this  pretty much relative 5 years till animal human studies till a drug develops to block hiv 1,

Offline Pepino2

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Re: Proteins that are used to halt HIV are identified.
« Reply #15 on: January 18, 2008, 12:42:48 AM »
Wow...this virus is dead meat.  This math, if correct....opens up the whole vulnerability of this bug.  For those of you who think "silent genes" don"t exist within our DNA...euh...we are full of them.  To think that all and any human gene manipulation will be picked up by Cancer...I don't beleive in it.   Great Science today!

I am soooo proud of the research effort happening right now.  Wow.

Bye Bye HIV.  :)

Offline John2038

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Re: Proteins that are used to halt HIV are identified.
« Reply #16 on: January 19, 2008, 12:20:56 PM »
Now this job is done, they must prioritize the research to create new drugs against the major mutations.

Offline powerpuff

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Re: Proteins that are used to halt HIV are identified.
« Reply #17 on: January 24, 2008, 07:45:54 PM »
http://www.nytimes.com/2008/01/11/science/11hiv.html

another article...just worried if the proteins could be harmful or not yet needs to seen i guess we shall see

Offline bimazek

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Re: Proteins that are used to halt HIV are identified.
« Reply #18 on: January 28, 2008, 08:56:12 AM »
this is such good news because the virus is reproducing at perhaps a billion or trillion times faster than the cd4 cell that it infects so that if science finds a med that just slows down one of these genes that produce one of the proteins hiv needs it may shut off the production of hiv, dial down the production of hiv but let the cd4 cell live just fine

this is how the slow and non progressors deal with it, they have a change in one gene that codes one protein and this change in thier own gene this mutation causes the virus to not get enough of the protein it needs to reproduce so they virus cannot grow at least it grows so so slowly

for example many slow or non progressors have low low VL say less than 500 or even undetectable


Offline powerpuff

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Re: Proteins that are used to halt HIV are identified.
« Reply #19 on: January 28, 2008, 03:33:24 PM »
the on;y  part i was worried was the small line that stated blocking theses proteins could, harm or  kill humans, i guess they wiill have to continue with mouse studies if this is safe then progress to human studies this could take 5 years??? perhps more unknown ???

 


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