PNAS: accelerating the mismatch mutation rate helps to collapse the HIV virus

15 years ago, John Essigmann from the Massachusetts Institute of Technology and his colleagues from the University of Washington presented a new idea about the anti-AIDS drugs. They believed that if we could induce mutations in the virus, we could force the virus became weak and eventually die, which is also the strategy that our immune system used to against a number of viruses.

As expected, the researchers developed a drug that can cause high speed HIV mutants. However, according to the result of a small clinical trial in 2011, this drug did not clear the virus in patients. In a recent work published in ‘PNAS’ on July 28, the MIT researchers found the exact mechanism of a drug (KP1212) induced mutations in the HIV genome. Researchers believed this could help them to develop better drug versions to destroy the virus faster.

In this new article in PNAS, researchers found that KP1212 inserted itself into genome and switched between five kinds of different shapes and introduce mutations. Subsequently, using a genetic tools developed by Essigmann’s laboratory, researchers identified that KP1212 induced 10% of HIV genomic mutation. Based on these findings, Essigmann guessed if KP1212 are able to triple the mutation rate of HIV, it can clear the virus in patients in 1-2 years.

The researchers want to be able to carry out a longer-term KP1212 experiments, and are interested in developing new drugs-which can work at a faster speed-by changing some of the chemical characteristics of KP1212.

In the United States every one baby in 691 is born with Down syndrome. The patients of the disease have two copies of chromosome 21. People generally use the mouse model to study Down syndrome, but some researchers believe that the animal model is not ideal, because the human brain is much more complex. Most of this complexity comes from astrocytes, which are important for the brain's structure and nerve impulse conduction.

A research team from University of California, Davis used iPS technology to turn the skin cells of Down syndrome patient into astrocytes, and thus established a new disease models. Studies have shown that an inexpensive antibiotic can correct many of the abnormalities of Down syndrome. The related paper was published in the journal Nature Communications on July 20.

Using the new model for drug screening, the researchers found that the antibiotic minocycline can correct many abnormalities of astrocytes and help astrocytes to interact with neurons more healthy. Minocycline, a tetracycline antibiotic with anti-inflammatory ability, is generally used to treat bacterial infections, acne and arthritis. In recent years, more and more evidence indicated that minocycline have the potential to protect the nerves. This drug can enter the brain from the blood, and affect astrocytes.

IPS has helped researchers to build lots of neurodevelopmental and neurodegenerative diseases models, which are more suitable for pathology research and drug screening. Using the iPS technology, this research firstly discovered the key role of astrocytes in Down's syndrome, and identified the drug effective pathway.