A study published in the June 29 issue of the magazine Science provides the first evidence that Human Immunodeficiency Virus (HIV) can be fought by removing HIV's DNA from infected cells. A group of German scientists have created a mutant strain of a well-known enzyme that acts as a pair of scissors to "snip out" HIV's DNA sequence that was previously inserted into the larger human cell DNA as part of an HIV infection.
What makes HIV so insidious is that it insinuates its own DNA into that of the host cell. HIV's DNA hijacks the cell's reproductive mechanism to produce more of the HIV virus. When that host cell divides more of the HIV virus is produced. Current treatments for HIV focus on the use of anti-viral drugs to suppress the HIV virus before it enters cells.
The German researchers, Indrani Sarkar, Ilona Hauber, Joachim Hauber, and Frank Buchholz of the Max Planck Institute for Molecular Cell Biology and Genetics and the University of Hamburg's Heinrich Pette Institute for Experimental Virology and Immunology created a variant of the Cre recombinase enzyme, know as Tre. Cre looks for specific sites, designated lox P, on a cell's DNA which indicate the beginning and end of a section of DNA. The Cre enzyme destroys those sites causing the DNA segment to be severed from the rest of the cell's DNA. The Tre enzyme was created by exposing Cre to the HIV virus and allowing Cre to evolve into an enzyme that can detect a segment of HIV DNA in a cell's strand of DNA.
While this is a very promising line of research, much work remains to be done to make this an effective treatment for HIV. Enzymes such as Cre/Tre are notoriously hard to introduce into the body without the body's natural processes destroying them. Further, this study was conducted on only one species of HIV, HIV-1. It remains to be seen if this enzyme will be equally effective on the other species of HIV, HIV2. Lastly, Tre is a very slow-acting enzyme. In the experiments conducted by Sarkar, et al, Tre required three months to remove all traces of HIV from cultured human cervical cells.
Alan Engelman, a molecular virologist at the Dana-Farber Cancer Institute in Boston wrote an accompanying editorial in the same issue of Science. "This is the first demonstration of actual removal of the integrated virus from cells. The results are promising," he says, "but researchers have to make sure the slow-acting Tre enzyme works on real-world strains of HIV and figure out how to safely and precisely administer it in gene form to give it time to snip."
Ideally, Engelman wrote, researchers would like to find a way to send Tre enzymes into the small number of white blood cells, known as T cells, that carry the virus without producing new viral particles, which allows HIV to hide from both antiviral drugs and the immune system.Powered by Sidelines