The extreme diversity of human immunodeficiency virus (HIV) strains is a major obstacle to anti-AIDS vaccine elaboration or the development of new treatments against the disease. IRD scientists, working jointly with other institutes (1), used statistical methods to determine the adaptive molecular mechanisms the virus deploys to avoid neutralization by the host immune defences. This adaptive molecular evolutionary strategy, based on genetic variability, proved to be a feature common to the different HIV subtypes. The virus apparently uses the great variety of its envelope-protein receptor binding sites, which have the role of fixing large complex carbohydrate molecules in the form of glycans, to provide protection against the host’s antibodies. These sugars are large structures that apparently block the way of human antibodies that would otherwise fix on to the virus, without hindering these envelope proteins in their function of attaching the virus to the host cell. These results open the way to potential ways of tackling AIDS.
In humans, the AIDS virus HIV manifests extreme genetic variability. It is particularly virulent, probably because its introduction into populations is recent (2). It has a potential for rapid evolution, at both population and individual scales, owing to a mutation rate among the highest in the living world, and to its recombination capacity. This high evolutionary potential is one of the major obstacles hindering the development of an effective vaccine. Starting from the principle that this mutation-based evolution of the virus is a response to selective pressures exerted by the host immune response (thought to be the dominant evolutionary force) , IRD researchers and their project partners (1) attempted to determine, at the molecular scale, the adaptive mechanisms at work and their comparative occurrence between the different HIV groups and subtypes. They used powerful statistical techniques (the codon-based maximum likelihood method) to investigate and compare the evolution of 3 major genes of the HIV genome, gag, pol and env. They did this for several HIV subtypes. They were able to confirm that the virus followed a dynamic adaptation strategy, based on the deployment of a shield of complex carbohydrates (glycans) to block antibody binding and thus provide protection against the host immune response.
Among the mutations randomly affecting the genome as a whole, those which influence the genes essential for viral survival and multiplication appear to be systematically selected against (negative selection). The gag gene, which codes for the proteins of the capsid (containing the genome and the viral proteins) and the pol gene, which allows synthesis of enzymes essential for virus replication, thus appear highly conserved and stable from one subtype to another.
Bénédicte Robert | EurekAlert!
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