January 23, 2013
Researchers have come up with a technique that makes certain types of immune cells resistant to HIV infection. The researchers believe that this could lead to a new approach to removing HIV from the body.
According to James Stivers of Johns Hopkins University and one of the research scientists, DNA's code is comprised of four building blocks called nucleotides and usually abbreviated A, T, G, and C. Before a cell divides, DNA-copying enzymes string the nucleotides together based on existing templates so that each new cell receives its own copy of the genome. The T nucleotide, dTTP is similar to dUTP, another nucleotide that does not belong in DNA but gets inserted mistakenly instead of a T. To prevent the cell from being copied, most human cells have an enzyme that breaks down dUTP, keeping the levels very low. Another quality control measure is the enzyme hUNG2. This enzyme strips stray Us out of newly copied DNA strands, leaving holes that are filled by a different repair enzyme. Certain immune cells (resting cells) lack the first quality-control mechanism because they are not replicating and dividing.
When HIV invades a cell, it first makes a DNA copy of its own genome and inserts that copy into the host cell's genome. If there are dUTPs in the cell, they make their way into the new viral DNA and are later removed by hUNG2. Amy Weil, another of the researchers, measured dUTP levels and hUNG2 activity in different human cells grown in the laboratory and exposed them to HIV. The virus overcame cells with high dUTP and little hUNG2; cells with low dUTP and high hUNG2 were susceptible to HIV. Cells with high dUTP and high hUNG2 destroyed the virus, leaving its DNA filled with irreparable holes. Stivers believes that the study provides a new method of restricting HIV infection in non-dividing cells.
The study, "Uracil DNA Glycosylase Initiates Degradation of HIV-1 cDNA Containing Misincorporated dUTP and Prevents Viral Integration," is published online before print in the journal Proceedings of the National Academy of Sciences (2013, doi: 10.1073/pnas.1219702110).
The Economic Times