Scientists Expose Weak DNA in HIV

Ace905 writes "The National Institute of Allergy and Infectious Diseases announced Thursday that they had discovered a very promising 'weak spot' in the HIV virus. The HIV virus, a progenitor to full blown AIDS has eluded all attempts at a vaccine since it was discovered sometime in the 1970's. The major problem with developing a vaccine initially was isolating the virus. Conventional viruses are often defeated with existing drugs, or after being tested against new compounds. HIV has been unique, and staggering in it's ability to resist all attempts at treatment by mutating its own genetic code. HIV is able to resist, with great effectiveness, any drug or combination drug-therapy that is used against it."

Re:Fact check?

[DrKyle]

Also:

Scientists Expose Weak DNA in HIV

This is about finding a stable surface protein on the surface of HIV which may be a good target for the production of an antigen which would elicit a stable immune response as a number of people have antibodies which target the same site. This has nothing to do with DNA, the submitter is just biologically illiterate.

AIDS was discovered in 1981

[Gary W. Longsine]

The article summary needs further assistance. AIDS was identified in 1981. [wikipedia.org]

Re:Title of the story is wrong

[Gufry]

It is highly improbable that the mutation rate in that part of the genome is lower. The b12 epitope overlaps with part of the CD4 binding site (the point of the Nature article referenced by the BBC report), it is thought to be functionally important for engaging the receptor, mutations in the region are therefore selected against. It is a weak spot in HIV's defense against the host, but not 'weak DNA' which suggests, at least to me, that the DNA is somehow brittle. At any rate, the weak spot is the accessibility of the gp120 epitope to neutralizing antibodies, and that is the weakness that people want to exploit.

Re:The "HIV Virus"?

[Bender0x7D1]

From the article:

They have published an atomic-level image in Nature showing the antibody, b12, attacking part of a protein on surface of the virus.

So, yes it has been published - and Nature is a top-tier journal.

Re:Title of the story is wrong

[picob]

Antibodies against the b12 region are therefore potential vaccine candidates

b12 is a family of human antibodies that targets this viral protein gp120. gp120 is therefore the candidate for the vaccine. For vaccines we usually just inject viral protein(s) - as we would in this case - or a weak or dead form of the virus, and let the body make the antibodies (the b12 family in this case).

The talk about 'region' in this article probably refers to a site on the RNA of the virus: this region, encoding protein gp120, is not much changed by mutations - HIV codes genes in RNA since it's a retrovirus.

Also, since HIV targets the immune system, when someone has AIDS - the later stages of the disease in which the immune system is broken (targeted by HIV are T-cells) - vaccination may no longer work, since the immune system is no longer capable of producing antibodies, unless the T-cell count can be brought back to a level in which antibodies can be made.

Not DNA, RNA

[theshibboleth]

HIV is a retrovirus so any weak spots would be found in the RNA, not the nonexistent DNA. Interestingly, the BBC decided to sidestep this issue by not mentioning any nucleic acids at all.

Re:AIDS was discovered in 1981

[capebretonsux]

You're partly right. It was in 1981 when the disease was discovered/recognized. It was 1982 when the CDC renamed the disease 'AIDS'. Before that, it was known as GRID. (Gay-Related Immune Deficiency) The causitive virus itself wasn't discovered until 1983, and wasn't renamed 'HIV' until 1986.

(Splitting hairs, I know, but it's early and I haven't had my coffee yet...)

Interesting documentary

[Anonymous Coward]

For those of you that are interested in this story, I highly recommend the PBS Frontline documentary The Age of AIDS [pbs.org]. Being too young to really understand the events in the news which unfolded around its discovery, it truly changed the way I look at this disease.

Re:AIDS was discovered in 1981

[karnal]

At first I thought you were joking - the name "Gay-Related Immune Deficiency" just sounded made up. Turns out I'm mistaken:

http://en.wikipedia.org/wiki/Gay_Related_Immune_Di sease [wikipedia.org]

Link works, Slash puts the space in for display purposes.....

Re:The HIV virus has actually never been seen...so

[Unc-70]

What do you mean 'HIV has never been seen...'? That's just not true [sciencedirect.com]

Re:Fact check?

[elyons]

Also, HIV is a retrovirus. For this family of viruses, their genome spends the majority of its time, and especially as an infectious particle, as RNA. It is only after infraction does its genome get replicated into DNA (through a process known as reverse transcription using a virally encoding RNA dependent DNA polymerase known as reverse transcriptase.) After being copied into DNA, the pro-virus is then inserted into the host's genome where RNA molecules are made (transcribed) to make viral proteins and full length copies of its genome for packaging into new infectious viral particles. This is a very import aspect of the virus' life-cycle and has many implications for some of the anti-retroviral therapies [wikipedia.org] on the market.

Re:HIV's Dirty Little Secret

[Dachannien]

More specifically, HIV is a retrovirus. This means that as a standalone virus it contains RNA, but when it enters a cell, it uses reverse transcriptase to transcribe its RNA sequence into the equivalent DNA strand, which the cell's normal transcription/translation mechanism picks up and turns into the proteins and RNA that make the virus work.

It's the reverse transcription process that has a high error rate, which is why HIV's rate of mutation is so high. This results in a lot of nonviable DNA, but the virus takes years to work anyway. Eventually, some of these mutations result in a change in the proteins that are attacked by the various HIV drugs so that those drugs no longer work.

As for whether your statement about knowledge in treating various types of viruses is true or not, I don't know, but scientists do know an awful lot about HIV in particular. Each drug is meant to target a specific protein coded by the virus's genome. Being able to use drugs to target a "weak spot" (a spot that is brittle versus mutation) in the genome directly would be a major coup against the virus. This would be a great application for the grid computing mentioned in an earlier /. article. [slashdot.org]

Re:The HIV virus has actually never been seen...so

[moosejaw99]

I should have added to my post... Do no flame if you haven't seen the doc. I couldn't believe it myself...However I verified the facts and have questioned many experts on the subject. Please show me a photo of HIV, and not a computer model guessing what it looks like. Please show me the original study showing that HIV is the cause of AIDS. You won't be able to because they don't exist. Watch the show, and take the word of the experts who speak about it. Don't shoot the messenger. Also..this is only my second or third post on all of slashdot, so please don't confuse me with someone else.

Re:The HIV virus has been sequenced

[brit74]

> If you explore these areas, and find out that the HIV has actually never been seen, just the antibodies...

Uh, right. You know that the we've sequenced the HIV virus, right? Not only has it been sequenced, but it's been sequenced so many times that we can see the evolution of it's genetic code over time, and can tell which people infected which people. We can tell that the "Libyan seven" are innocent. We can tell that HIV evolved from SIV (the simian version of HIV) multiple times.

Re: Libyan Seven
"By looking at the genome sequence of the virus found in children at Bambino Gesu hospital, we established that the estimated date of the most common recent ancestor for each cluster predated March 1998, sometimes by several years."
http://observer.guardian.co.uk/world/story/0,,1974 040,00.html [guardian.co.uk]

"The story revolves around Dr. David Acer, a Florida dentist who died in 1990 from complications of AIDS. Dr. Acer's death would have been far from remarkable at the time -- the AIDS epidemic was quite visible by the late 1980s, and one death earned no more attention than any other. Dr. Acer's story, however, extends beyond his private life and into his practice. You see, Dr. Acer had multiple patients that had been diagnosed as infected with HIV within a couple of years of his death." Sequence analysis of HIV in his patients shows that he infected his patients.
http://scienceblogs.com/evolgen/2006/06/phylogeny_ friday_9_june_2006_1.php [scienceblogs.com]

Re:The HIV virus has actually never been seen...so

[zCyl]

Please show me a photo of HIV

one [epidemic.org]
two [redcross.org]
three [goodfeeling.nl]
four [scienceclarified.com] ...

They're not exactly tough to dig up these days if you know how to use google, so I must assume that you did not even do a rudimentary search for yourself before believing that documentary you watched.

Re:Title of the story is wrong

[picob]

yes, antibodies are produced by B-cells, but T-cells are required to enable B-cells to produce antibodies. In specific T-helper cells (CD4+) are targeted by HIV. from wiki:

When a B cell ingests a pathogen, it attaches parts of the pathogen's proteins to a class II MHC protein. This complex is moved to the outside of the cell membrane, where it can be recognized by a T lymphocyte, which is compatible with similar structures on the cell membrane of a B lymphocyte. If the B cell and T cell structures match, the T lymphocyte activates the B lymphocyte, which produces antibodies against the bits of pathogen, called antigen, it has presented on its surface.

source: http://en.wikipedia.org/wiki/B_cell [wikipedia.org]

pathogen - something that makes ill: a virus, bacterium, etc.
MHC - a family of proteins:
MHC class II is specific for B-cells and presents pathogenic proteins.

When the pathogen is presented on the B-cell membrane, the T-cells provide growth factors for B-cells that enable B-cell cell division, B-cells take up antibody bound to antigen, and therefore are able to present more antigen when their antibodies match better. In this process the antibodies are perfected (mutations can occur in regions encoding parts of the antibody).

Although a bit of topic, MHC class I is a surface protein that works as an ID to the immune system: it is unique per person, and presents proteins on the membrane surface that were trashed after use - proteins that were active inside the cell. MHC I shows to the immune system that the cell belongs to that person and the presenting of used proteins show whether they are in correct working order. Due to this protein, cancer cells are usually recognized and killed by the immune system in early stages. MHC molecules are also a reason why organ transplantation may fail.