( o the cell nucleus. There it becomes i...)Study shows that cells have a natural defense against HIV

The process of integration, which is absolutely required for a productive infection, begins with the help of an enzyme, integrase, which is supplied by HIV. But the job is finished by DNA repair enzymes provided by the host cell.

Yoder originally wanted to identify which repair enzymes were involved.

During these experiments, Yoder learned that cells with high levels of two proteins called XPB and XPD had lower levels of HIV provirus in their chromosomes. Both proteins help the cell repair damaged DNA.

Yoder, Fishel and their collaborators then introduced mutations into the genes for the two proteins, which crippled the proteins' ability to repair DNA. When cells with these mutations were then infected with HIV, they showed higher levels of provirus in their chromosomes.

"When we weakened a DNA repair pathway, we got more integration of the provirus," Yoder says. "This was a total surprise."

Next, the researchers wanted to learn whether the normal cells used in the study had lower proviral levels because they were making less HIV cDNA or because the HIV cDNA was being destroyed before it integrated.

To answer that question, the researchers used antiretroviral drugs known as non-nucleoside reverse transcriptase inhibitors (NNRTIs). These drugs prevent HIV from making the cDNA copy of its RNA genetic material. The researchers exposed newly infected cells to the drugs and then measured changes in the amount of cDNA over time.

These experiments showed that the cDNA was destroyed faster in cells with normal XPB and XPD compared to cells with mutant XPB or XPD. Cells with normal XPB protein lost half their proviral DNA after 4.6 hours, while cells with low levels of the protein lost half after about 7.7 hours
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Source:Ohio State University