A University College London study found two molecules in white blood cells with which HIV-1 collaborates in order to pass undetected from our immune systems. The results of the study, published in the journal Nature, offer important insight which can lead to more effective therapeutic strategies by targeting molecules that do not mutate but are essential for HIV-1 to hide and evade the immune system attack.
Since the discovery of the Human immunodeficiency virus (HIV) in the early 1980’s, virologists have been revealing several aspects of HIV biology. The genetic material of this virus is RNA. When HIV enters macrophages it uses the cell machinery to make double-stranded DNA and prepare material that will be used to create new viral particles. The transcription of RNA to DNA usually triggers an innate immune response which kills viruses, but HIV somehow does not trigger an immune response. Most drugs against HIV usually block the entry of a virus into the cell, or target enzymes important for HIV cycle. But all these characteristics of the HIV are continuously changing (mutating) and offer insensitivity of the virus to drugs, and the virus can remain undetected.
A group of scientists at the University College in London have made HIV mutants in order to study them. They have found that two of these HIV mutants cannot replicate in macrophages and subsequently triggers the production of interferon beta (IFN-β), an antiviral hormone which attacks viruses. The research team found that HIV-1 associates with two molecules (CPSF6 and cyclophilin) in macrophages to conceal its replication and evade the immune response. When they blocked this association using their mutants, or when they removed these molecules, the natural immune system was activated and could attack the virus. Remarkably, when they used an experimental drug, a modified version of cyclosporine, the HIV replication is uncloaked and the immune response is kicked off.
This is very important knowledge towards the fight against HIV. By targeting molecules of our own cells, which do not mutate so rapidly but are important for the virus, scientists can minimize the possibility of resistance to HIV therapies. “There’s a great deal more research needed, but the potential for this approach is huge – as a possible treatment in itself, but also as a complement to existing therapies” says the lead author of the study, Professor Greg Towers, a Wellcome Trust Senior Research Fellow at UCL.
“The hope is that one day we may be able develop a treatment that helps the body to clear the virus before the infection is able to take hold.”