Research

Illuminating the Path to Anti-HIV Vaccines

14.3.2017 | A team led by AcademiaNet scientist Anne Dell has revealed the exact makeup of part of the sugar coat that envelopes HIV. The authors findings, recently published in the journal Scientific Reports, should facilitate the further optimisation of effective neutralising antibodies against the virus.
Virus HIV
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Virus HIV

HIV is a master of disguise. Not only does the virus change its makeup continuously through mutations in its DNA, but it also hides behind a thick layer of sugar residues, called glycans. Antibodies that can neutralise HIV have to recognise its coat proteins despite or because of these glycans. It is therefore important to know the exact composition and structure of the virus' sugar coat to be able to integrate these insights into the development of an HIV vaccine.


Now, a team of UK and US scientists led by Anne Dell, based at Imperial College London, have succeeded in providing a detailed map of the sugar coat bound to the HIV surface protein gp120. Even though analysis of the glycan coat of HIV had previously been performed, the authors’ analysis breaks new ground in two respects: theirs is the first study analysing material from actual viral particles rather than from artificially produced gp120 protein and in addition, nobody before had systematically investigated where exactly the glycans were binding on gp120.


The authors first produced HIV viral particles by infecting human T-cell lymphoma lines with the virus. HIV multiplied within these host cells, and the authors were able to harvest the resulting viruses, which harbored large amounts of gp120. After purification of gp120, Dell and her team used two complementary techniques to analyse the glycan molecules bound to the protein. In their first approach, they added sugar-cleaving enzymes to the purified gp120 to shave off the glycans. In the second method, the researchers combined sugar-cleaving and protein-cleaving enzymes. After each enzymatic treatment, the researchers analysed the virus particles using mass spectrometry. This enabled the team not only to map exactly what kinds of glycans were bound to gp120, but also revealed where on the gp120 protein the glycan molecules were binding. They found that gp120 has glycans on as many as 24 distinct sites, and that these sugar molecules are predominantly of the oligomannose type.


The results of Dell and her colleagues provide a detailed molecular picture of where broadly neutralising HIV antibodies could bind. This, the authors say, will contribute to the development of more effective vaccines. Also, the technique which Dell and her colleagues have developed may prove extremely useful in future studies aimed at elucidating the structure of the outer coat of HIV.


 


Written by Neysan Donnelly for AcademiaNet   (© AcademiaNet)

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