Hopes for Natural Anti-HIV Drugs

New research has found that two proteins that repair cellular DNA can also destroy HIV replication in the human cell.

Before infecting a cell, HIV carries the genetic material ribonucleic acid (RNA). Once inside, HIV makes a copy of its genes in the form of DNA. This DNA copy, or cDNA, then travels to the cell nucleus, where it is integrated as a provirus into the cell's DNA and can reproduce.

Researchers introduced mutations into genes encoding proteins XPB and XPD, which help cells to repair damaged DNA. Cells carrying this mutation showed higher levels of HIV provirus in their chromosomes. Next, the researchers introduced a drug known to destroy cDNA. Among normal cells, cDNA destruction occurred at a faster rate than among cells with silenced XPB and XPD genes, suggesting the proteins were able to destroy cDNA before it was able to incorporate itself into cellular DNA.

"Overall, our results indicate that these two DNA repair proteins participate in the destruction of HIV cDNA in cells," said lead author Richard Fishel, a professor at Ohio State University. "This process reduces the pool of HIV cDNA that can integrate into host chromosomes, thereby protecting cells from infection."

Researchers hope the findings will lead to drugs that might help boost the process of cDNA destruction. "HIV treatments that target cellular components should be far less likely to develop resistance," said Fishel.

"The more opportunities we have to attack [HIV], the better," said Mary Lima of the HIV charity Terrence Higgins Trust. "However, we need to be cautious as modifying proteins within healthy immune cells could have unforeseen effects on the immune system as a whole."

The full study, "The DNA Repair Genes XPB and XPD Defend Cells from Retroviral Infection," was published in the Proceedings of the National Academy of Sciences (2006;103(12):4622-4627).

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