HIV breaches macrophage defences, could be step towards cure

A team led by UCL researchers has identified how HIV is able to infect macrophages, a type of white blood cell integral to the immune system, despite the presence of a protective protein. They discovered a treatment that can maintain macrophage defences which could be a key part of the puzzle of reaching a complete cure for HIV/AIDS. Macrophages make an antiviral protein called SAMHD1, which prevents HIV from replicating in these cells - except for when the protein is switched off, as part of a natural process discovered by the UCL-led team. 'We knew that SAMHD1 is switched off when cells multiply, but macrophages do not multiply so it seemed unlikely that SAMHD1 would be switched off in these cells,' said Professor Ravindra Gupta (UCL Infection & Immunity), the senior author of the paper. 'And yet we found there's a window of opportunity when SAMHD1 is disabled as part of a regularly-occurring process in macrophages.' Lead author of the EMBO Journal study, Dr Petra Mlcochova (UCL Infection & Immunity) said: 'Other viruses can disable SAMHD1, but HIV cannot. Our work explains how HIV can still infect macrophages, which are disabling SAMHD1 by themselves.' The reason why SAMHD1 gets switched off remains to be determined, but the authors suggest it might be done in order to repair damaged DNA, part of the normal functioning of the macrophage. In a further part of the study, the researchers discovered how to close this window of opportunity by treating the cells with HDAC inhibitors, which are sometimes used in cancer treatments.