Mutational networks of escape from transmitted HIV-1 infection
dc.contributor.author | Akand, EH | |
dc.contributor.author | Maher, SJ | |
dc.contributor.author | Murray, JM | |
dc.date.accessioned | 2020-12-09T10:14:59Z | |
dc.date.issued | 2020-12-07 | |
dc.description.abstract | Human immunodeficiency virus (HIV) is subject to immune selective pressure soon after it establishes infection at the founder stage. As an individual progresses from the founder to chronic stage of infection, immune pressure forces a history of mutations that are embedded in envelope sequences. Determining this pathway of coevolving mutations can assist in understanding what is different with the founder virus and the essential pathways it takes to maintain infection. We have combined operations research and bioinformatics methods to extract key networks of mutations that differentiate founder and chronic stages for 156 subtype B and 107 subtype C envelope (gp160) sequences. The chronic networks for both subtypes revealed strikingly different hub-and-spoke topologies compared to the less structured transmission networks. This suggests that the hub nodes are impacted by the immune response and the resulting loss of fitness is compensated by mutations at the spoke positions. The major hubs in the chronic C network occur at positions 12, 137 (within the N136 glycan), and 822, and at position 306 for subtype B. While both founder networks had a more heterogeneous connected network structure, interestingly founder B subnetworks around positions 640 and 837 preferentially contained CD4 and coreceptor binding domains. Finally, we observed a differential effect of glycosylation between founder and chronic subtype B where the latter had mutational pathways significantly driven by N-glycosylation. Our study provides insights into the mutational pathways HIV takes to evade the immune response, and presents features more likely to establish founder infection, valuable for effective vaccine design. | en_GB |
dc.description.sponsorship | Australian Research Council (ARC) | en_GB |
dc.identifier.citation | Vol. 15 (12), article e0243391 | en_GB |
dc.identifier.doi | 10.1371/journal.pone.0243391 | |
dc.identifier.grantnumber | DP180103893 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/123971 | |
dc.language.iso | en | en_GB |
dc.publisher | Public Library of Science (PLoS) | en_GB |
dc.relation.url | https://doi.org/10.5061/dryad.r19c2 | en_GB |
dc.rights | © 2020 Akand et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | en_GB |
dc.title | Mutational networks of escape from transmitted HIV-1 infection | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2020-12-09T10:14:59Z | |
dc.description | This is the final version. Available on open access from the Public Library of Science via the DOI in this record | en_GB |
dc.description | Data availability: The sequence data are available in the Dryad Data Depository, DOI: doi:10.5061/dryad.r19c2 Data files: HIV envelope sequences Seroconverter HIV subtype B envelope sequences. | en_GB |
dc.identifier.eissn | 1932-6203 | |
dc.identifier.journal | PLoS ONE | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2020-11-19 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2020-12-07 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2020-12-09T10:13:07Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2020-12-09T10:15:08Z | |
refterms.panel | B | en_GB |
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Except where otherwise noted, this item's licence is described as © 2020 Akand et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.