Scientists have discovered a molecular 'invisibility cloak' that
enables HIV, the virus that causes AIDS, to hide inside cells of
the body without triggering the body's natural defence
systems.
Their study shows how 'uncloaking' the virus using an
experimental drug triggers an immune response that stops the virus
from replicating in cells grown in the laboratory. The findings
could lead to new treatments and help to improve existing therapies
for HIV infection.
The innate immune system is the body's first line of defence
against infection and incorporates an alarm system present in all
cells of the body that detects the presence of 'foreign' material
from invading bacteria and viruses. When the alarm is tripped, the
infected cell begins an antiviral programme and sends out warning
signals to alert other cells that a virus is around.
HIV infects vital cells of the immune system, so its ability to
replicate undetected without triggering this alarm system has
puzzled scientists since the discovery of the virus.
The team identified two molecules inside host cells that are
recruited by HIV after infection that stop the virus from
reproducing its genetic material too early. The effect is to shield
the virus from the alarm system and stop the innate immune system
from kicking into action.
In the absence of these molecules, whether caused by depletion
from infected cells or by blocking their recruitment using an
experimental drug, HIV is exposed to the alarm system and an
antivirus immune response is triggered. Targeting the cloaking
molecules and not the virus itself makes it much more difficult for
the virus to mutate and become resistant to this treatment
approach, a significant problem with standard HIV
therapies.
Professor Greg Towers, a Wellcome Trust Senior Research Fellow
at UCL (University College London), said: "HIV is extremely adept
at hiding from our body's natural defences, which is part of the
reason the virus is so dangerous. Now we've identified the virus'
invisibility cloak, and how to expose it, we've uncovered a
weakness that could be exploited for new HIV treatments.
"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. We're also interested
to see whether blocking these cloaking molecules can help to boost
immune responses to experimental vaccines against HIV or be used to
protect against HIV transmission.
"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."
The experimental drug used in the study is based on
cyclosporine, a drug that is widely used to prevent organ rejection
in transplant patients because of its ability to dampen the immune
response. Cyclosporines have been shown to block the replication of
HIV and other viruses but are not suitable for treating infected
patients because of their negative effects on the immune
system.
The team used a modified version of the drug, which blocks the
effects of the two cloaking molecules without suppressing immune
activity.
Dr Kevin Moses, Director of Science Funding at the Wellcome
Trust, said: "In 2012, 2.3 million people were newly infected with
HIV. While existing treatments are helping people with HIV to live
longer and healthier lives, the challenge of adherence to treatment
programmes means that drug resistance remains a threat and the
virus continues to burden the world's poorest communities.
Understanding how HIV interacts with the body's own defences might
just be crucial for developing the best approaches to
therapy."
The paper, HIV-1 evades innate immune recognition through specific co-factor
recruitment, is published
in Nature.