Posted on Feb 05, 2019, 9 p.m.
The HIV virus mutates in order to evade broadly neutralizing antibodies making it difficult to prevent and treat HIV infection. Fred Hutchinson Cancer Research Center scientists have constructed an atlas of HIV mutations which may provide insight to boost ongoing searches for effective vaccines.
The HIV envelope is a layer of glycoproteins that shuttles the virus into host cells and interact with antibodies even in areas the antibodies can’t reach, the team showed that mutations occur in the envelope, findings were published in the journal Immunity.
The viral envelope has been focussed on by researchers working towards developing vaccines and treatments, studying the sites where outside proteins interact with neutralizing antibodies; some vaccines have been developed aimed at triggering broadly neutralizing antibodies with limited success. During immunotherapy clinical trials there has been viral escape from each antibody, it is important to understand how escape occurs.
The team focused on functional epitopes which are the areas of neutralizing antibodies that affect their ability to block HIV; deep mutational technology was used to scan and create a library of viruses with all possible mutations that can occur in the gene that encodes HIV’s envelope protein.
Running all the mutated viruses through a series of broadly neutralizing antibodies the team observed how each mutation affected their ability to escape immune attack; further investigation pinpointed areas of the structural epitope that contribute to neutralizing antibodies ability to block HIV, according to the team.
The team believes their atlas will assist researchers to design therapeutics by choosing antibodies for which HIV has limited escape routes; and the technique may be applied to other viruses which are also the subject of research centered around developing vaccines that trigger broadly neutralizing antibodies; as the atlas allows for better understandings of the relationships between function and structure of epitopes.
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