A traditional African AIDS awareness badge. The new technique could be the first step in developing a cure for HIV, which is ravaging populations across Africa.
Credit: iStockphoto
CHICAGO: In a breakthrough that could potentially lead to a cure for HIV infection, scientists have discovered a way to remove the virus from infected cells.
The scientists engineered an enzyme which attacks the DNA of the HIV virus and cuts it out of the infected cell, according to a study published today in the U.S. journal Science.
The enzyme is still far from being ready to use as a treatment, the authors warned, but it offers a glimmer of hope for the more than 40 million people infected worldwide.
Cut it out
"A customized enzyme that effectively excises integrated HIV-1 from infected cells in vitro might one day help to eradicate (the) virus from AIDS patients," Alan Engelman, of Harvard University's Dana-Farber Cancer Institute, in Boston, U.S., wrote in an article accompanying the study.
Current treatments focus on suppressing the HIV virus in order to delay the onset of AIDS and dramatically extend the life of infected patients. What makes HIV so deadly, however, is its ability to insert itself into the body's cells and force those cells to produce new infection.
"Consequently the virus becomes inextricably linked to the host, making it virtually impossible to 'cure' AIDS patients of their HIV-1 infection," Engelman explained.
That could change if the enzyme developed by a group of German scientists can be made safe to use on people. That enzyme was able to eliminate the HIV virus from infected human cells in about three months in the laboratory.
The researchers engineered an enzyme called Tre which removes the virus from the genome of infected cells by recognizing and then recombining the structure of the virus's DNA.
This ability to recognize HIV's DNA might one day help overcome one of the biggest obstacles to finding a cure: the ability of the HIV virus to avoid detection by reverting to a resting state within infected cells which then cease to produce the virus for months or even years.
"Proof of principle"
"Numerous attempts have been made to activate these cells, with the hope that such strategies would sensitise the accompanying viruses to antiviral drugs, leading to virus eradication," Engelman wrote. "Advances with such approaches in patients have been slow to materialize."
New experiments must be designed to see if the Tre enzyme can be used to recognize these dormant infected cells, he wrote.
"Although favourable results would represent perhaps only a baby step toward eventual use in patients, the discovery of the Tre recombinase proves that enzymatic removal of integrated HIV-1 from human chromosomes is a current-day reality," he said.
The researchers who developed the enzyme were optimistic about their ability to design additional enzymes which would target other parts of the virus's DNA.
However they warned that there were significant barriers to overcome before the enzyme could be used to help cure patients.
"The most important, and likely most difficult, among these is that the enzyme would need efficient and safe means of delivery and would have to be able to function without adverse side effects," wrote lead author Indrani Sarkar of the Max Planck Institute for Molecular Cell Biology and Genetics in Dresden.
"Nevertheless the results we present offer an early proof of principal for this type of approach, which we speculate might form a useful basis for the development of future HIV therapies," Sarkar concluded.
HIV uses RNA not DNA
The report states misleadingly: "The researchers engineered an enzyme called Tre which removes the virus from the genome of infected cells by recognizing and then recombining the structure of the virus's DNA."
This is a bit sloppy. HIV, a retrovirus, contains a double stranded RNA with 9 genes. Inside the invaded cell, the RNA is transcribed into DNA and spliced into the host nucleus.
See http://www.avert.org/virus.htm:
"Three of the HIV genes, called gag, pol and env, contain information needed to make structural proteins for new virus particles. The other six genes, known as tat, rev, nef, vif, vpr and vpu, code for proteins that control the ability of HIV to infect a cell, produce new copies of virus, or cause disease."
The new discovery apparently hunts down this compiled and integrated DNA and snips it back out.
Yes but the genetic
Yes but the genetic information is reverse transcribed (to make DNA from RNA,) and then this DNA is integrated into the host DNA. Incorporating RNA into a DNA strand wouldn't be feasible.
separting hype from reality
An expert researcher pal comments:
Since this is a field I am pretty familiar with wanted to give a short perspective to separate the hype from reality.
While this is a major achievement and a genetic tool breakthrough, it is far far from a cure for HIV. The enzyme that has been developed is a variant of Cre recombinase, which recombines and removes sequences flanked by a particular motif called loxP sites (an 8 bp sequence). Using a very clever protein evolution technology the authors were able to adapt Cre to recombine and therefore excise HIV LTR (long term repeats that flank HIV at the beginning and end of its genetic code). This of course has the potential to snip out HIV that has integrated into genome of target cells (typically CD4+ T cells) that also remain in resting state and sustain a pool of latently infected cells. This is the main reason why HIV is not currently curable. The drugs can eliminate virtually all replicating virus but those that remain dormant are part of the host genome and are hidden from the effects of drugs that mostly target HIV proteins.
There are two major problems with this approach being applied for clinical use. First is the delivery of the gene encoding this novel enzyme or the protein into cells that have latent integrated virus. This currently not possible, even with viral vectors as these resting T cells are highly resistant and also there is no way to identify them as infected cells. Only conceivable way for this type of therapy would be introduction of the enzyme into stem cells and injecting these back into patients with the hope that, eventually they can replace the T cells, which may never happen completely. Of course this approach is also so impractical that it would be an academic exercise at best.
Second problem is that the authors have not yet tested whether this enzyme will actually work in primary cells especially resting T cells. This is not guaranteed since the resting cells will have a much more compact chromatin structure and the enzyme may not be able to access the integrated HIV as easily. In fact in a paper we published several years ago, we found that the Cre recombinase was most efficient in cells that are in cell cycle.
I do however think this is a fantastic proof of principle for developing proteins with novel functions and also will be very useful as a tool for studying the mechanisms of retroviral integration.
help
im an hiv victim, is there a possibility that i could be cured? plz? answer my question?
HIV victim
HIV victim, HIV does not necessarily mean you have aids or any other harmful conditions. The human immunodeficiency virus weakens the body for attack from other nasties such as AIDS etc. At the moment there is no known cure but if you're concerned contact your GP or doctor.
yes, u'll be cured one day if u live till that day
a lot of progress is underway towards finding a cure for hiv but truth is that not all of us living with the virus today will see that day when cure for hiv will become a reality. so live well and remain positive, hope and pray that u'll live long enough to see the days when hiv will become history. cheers
cure
just a thought, i had a dream that the cure was in the molecular enzymes of mosquitoes, particularly female anopheles mosquitoes. can someone please look into that for me?
Yes, I'll get right on that.
Yes, I'll get right on that.
hiv
m wating for the day bt want to ask hom much time to get cure for hiv aids