The key to
future HIV treatment could be hidden right in our own genes. Everyone who
becomes infected deploys defence strategies, and some even manage to hold the
virus at bay without any therapy at all. This immune system struggle leaves its
mark within the pathogen itself – genetic mutations that indicate how the virus
reacted to its host's attacks. Scientists from EPFL and the Vaud university
hospital centre (UNIL-CHUV) retraced the entire chain of events in these
battles, from the genome of the virus to the genome of the victim. They have
created the first map of human HIV resistance. The goal of their research,
which has been published in the journal eLife, is to
find new therapeutic targets and to enable individualised treatment strategies.
immune system is constantly developing strategies to fight HIV. Unfortunately,
"the genome of the virus also changes rapidly, at a rate of millions of
mutations a day," explains Jacques Fellay, co-author and EPFL researcher.
In the majority of cases, the pathogen finds an effective strategy via this
the virus is faced with a tougher opponent. It resists, but its ability to
replicate is compromised. "The virus survives but replicates more slowly,
and thus its capacity for destruction is in some sense neutralised," says
strains of HIV that have been living in human hosts, the researchers can
identify specific genetic mutations. These are like scars that each bear
witness to a very specific attack launched by the immune system. What are the
human genes involved in these defence strategies? And which, among all our
genetic variations, predispose us to increased HIV resistance or, on the
contrary, increased vulnerability? The scientists developed a method that
allowed them to find answers to these questions.
To draw up
the first map of human HIV resistance, the researchers had to analyse an
enormous amount of data. They studied various strains of HIV from 1 071
seropositive individuals. They crossed more than 3000 potential mutations in
the viral genome with more than 6 million variations in the patients' genomes.
Using supercomputers, they studied all these possible combinations and identified
correspondence between patients.
had to study the virus before the patient had undergone treatment, which is far
from easy," says Fellay. This meant they had to search in data banks
established in the 1980s, before effective therapies were made available.
indirect method made it possible to obtain the most complete global overview to
date of human genes and their implications in terms of HIV resistance. It
allows us to not only better understand how we defend ourselves from attack but
also how the virus adapts itself to our defence mechanisms. "We now have a
true database that tells us which human genetic variation will induce which
kind of mutation in the virus", explains Amalio Telenti, co-author and
research has two major implications. New therapies could be developed based on
studying humans' natural defences, particularly those that result in a reduced
replication of the virus. In addition, the scientists hope that by profiling
the genome of HIV-infected individuals, it will be possible to develop
individually targeted treatments that take into account the patients' genetic
strengths and weaknesses.