Scientists have unearthed the ‘lock and key’ that facilitates HIV to enter cell’s nucleus, disable the immune system and cause AIDS.
The finding provides a potential new target for anti-AIDS drugs that could be more effective against drug-resistant strains of the virus.
HIV is transmitted through bodily fluids, primarily infected blood or semen. Once inside the bloodstream, the virus infects key components of the immune system including cells known as macrophages.
It works its way into the nucleus of the macrophages, where it integrates itself into the cell’s DNA, allowing it to replicate and spread throughout the body.
To access the DNA, the HIV must pass through the Nuclear Pore Complex, a gateway into the nucleus. Until now, the mechanism that allows the virus to pass through this gateway was unknown.
Now, a team of scientists from UCL (University College London), the University of Pennsylvania School of Medicine and the Laboratory of Molecular Biology in Cambridge, has identified a vital component of this mechanism.
A part of the HIV virus called the capsid protein, acting like a key, binds to Nup358, a protein on the nuclear pore complex, unlocking the gateway and granting the virus access to the DNA.
“In our research, we have found the ‘lock and key’ that allow HIV to enter a cell’s nucleus. Once inside, the virus can begin to replicate itself, spreading almost unchecked throughout the body. If we were able to block this entry with a drug – in effect, to change the locks – then we could stop this spread,” said Professor Greg Towers, who led the research.
According to first author Dr Torsten Schaller, targeting proteins in the host, rather than in the virus itself, has added benefits.
The study has been published in the journal PLoS Pathogens.