Hopes for natural anti-HIV drugs

 

Scientists have discovered a previously unknown mechanism that cells use to fight off HIV.

Two proteins that normally help repair cellular DNA were found also to destroy DNA made by HIV after it enters a human cell which it requires to survive.

It is hoped the breakthrough could lead to treatments to which the virus might be less able to adapt.

The Ohio State University study appears in Proceedings of the National Academy of Sciences.

Currently, doctors treat HIV using combinations of drugs that target the virus itself, blocking its ability to reproduce and spread.

They have proved to be very effective, but there are concerns that HIV, deploying its ability to mutate rapidly, is becoming resistant to their impact.

Lead researcher Professor Richard Fishel said: "Our findings identify a new potential drug target, one that involves a natural host defence.

"HIV treatments that target cellular components should be far less likely to develop resistance."

 

Integration into cell

Before HIV infects a cell, it carries its genetic material in the form of RNA, or ribonucleic acid.

Once inside a cell, the virus makes a copy of its genes in the form of DNA.

This DNA copy - known as cDNA - then travels to the cell nucleus, where it becomes integrated, as a provirus, into the cell's own DNA, and can begin to reproduce.

The Ohio team found cells with high levels of two particular proteins had lower levels of HIV provirus in their chromosomes.

Both proteins - called XPB and XPD - help cells to repair damaged DNA.

The researchers introduced mutations into the genes for the two proteins, which crippled their ability to repair DNA.

Cells carrying the mutations showed higher levels of HIV provirus in their chromosomes.

 

Exposed to drugs

Next, the researchers exposed cells newly infected with HIV to a drug known to destroy cDNA.

They found cDNA destruction occurred at a faster rate among cells with normal XPB and XPD than in those with the mutant - and effectively disabled - versions of the proteins.

This suggested that the proteins were able to destroy cDNA before it was able to incorporate itself into the cell's own DNA.

Professor Fishel said: "Overall, our results indicate that these two DNA repair proteins participate in the destruction of HIV cDNA in cells.

"This process reduces the pool of HIV cDNA that can integrate into host chromosomes, thereby protecting cells from infection."

The researchers are now working to learn how the proteins destroy the HIV cDNA.

They hope their work could lead to drugs that might help the proteins destroy more HIV cDNA and in shorter time.

Mary Lima, of the HIV charity Terrence Higgins Trust, said: "This approach does sound interesting as it works at a very early stage in the life-cycle of the virus and could be effective in combination with currently approved drugs.

"The more opportunities we have to attack the HIV virus, the better.

"However, we need to be cautious as modifying proteins within healthy immune cells could have unforeseen effects on the immune system as a whole."