Macrophages are a type of white blood cell integral to the immune
system. They make an antiviral protein called SAMHD1, which prevents human immunodeficiency virus (HIV) from replicating in these cells.
A team led by UCL researchers has identified how HIV is able to
infect macrophages despite the presence of a protective protein. They discovered a
treatment that can maintain macrophage defenses 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.’
HIV from replicating except for when the protein SAMHD1 is
switched off, as part of a natural process discovered by the UCL-led
"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.
"Our findings could help explain why some people undergoing
anti-retroviral therapy for HIV continue to have HIV replication in the
brain, as the infected cells in the brain are typically macrophages.
While this is a barrier to achieving control of HIV in just a minority
of patients, it may more importantly be a barrier to a cure," Gupta
The researchers say that macrophages can be an important reservoir
of HIV infection that lingers away from the reach of existing
treatments. Once a macrophage is infected, it will continually produce
the HIV virus, so cutting off that point of infection within the body
could be an important step towards safeguarding the entire immune
HDAC inhibitors may be particularly helpful as they're already
known to reactivate latent HIV cells, thus making the virus vulnerable
to the body's defences, especially if supported by anti-retroviral
The series of tests involved cultures of macrophages derived from
human cells in vitro, which responded well to HDAC inhibitor treatment,
as well as macrophages residing in mouse brain tissues.