Researchers in the United Kingdom have shed new light on how the body's proteins can fight the human immunodeficiency virus (HIV-1). The study, presented in journal Nature, was funded in part by the NIMBL ('Nuclease immune mediated brain and Lupus-like conditions: natural history, pathophysiology, diagnostic and therapeutic modalities with application to other disorders of autoimmunity') project, which is backed with EUR 5.4 million under the Health Theme of the EU's Seventh Framework Programme (FP7).
Researchers from the University of Manchester and the Medical Research Council's National Institute for Medical Research in the United Kingdom offer us a novel plan of new treatments to fight HIV infection.
In an earlier study, a team of scientists from France and the United States observed that a protein named SAMHD1 can hinder HIV from replicating in a group of white blood cells called myeloid cells. In this latest research, the British team has demonstrated how SAMHD1 prevents the virus from replicating itself within these cells, paving the way for development of drugs that imitate this biological process to ensure that HIV cannot replicate in the sentinel cells of the immune system.
The team expressed SAMHD1 in Escherichia coli strain BL21 and purified using Strep-Tactin affinity and size-exclusion chromatography. They incorporated determination selenium into the protein by adding defined culture media with selenomethionine. The researchers also evaluated nucleic acid hydrolysis products with gel electrophoresis using 15% polyacrylamide gels for deoxyribonucleic acid (DNA) substrates and 1.5% agarose gel for ribonucleic acid (RNA) substrates.
'HIV is one of the most common chronic infectious diseases on the planet, so understanding its biology is critical to the development of novel antiviral compounds,' says senior author Dr Michelle Webb, leader of the study in the School of Biomedicine at the University of Manchester.
'SAMHD1 has been shown to prevent the HIV virus [from] replicating in the certain cells but precisely how it does this wasn't known,' she explains. 'Our research has found that SAMHD1 is able to degrade deoxynucleotides, which are the building blocks required for replication of the virus. If we can stop the virus from replicating within these cells, we can prevent it from spreading to other cells and halt the progress of the infection.'
Commenting on the study's findings, co-author Dr Ian Taylor from the National Institute for Medical Research says: 'We now wish to define more precisely, at a molecular level, how SAMHD1 functions. This will pave the way for new therapeutic approaches to HIV-1, and even vaccine development.'