{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T04:13:12Z","timestamp":1747195992591,"version":"3.40.5"},"reference-count":41,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T00:00:00Z","timestamp":1607299200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Australian Research Council Discovery Project","award":["DP180103893"],"award-info":[{"award-number":["DP180103893"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1371\/journal.pone.0243391","type":"journal-article","created":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T22:04:54Z","timestamp":1607378694000},"page":"e0243391","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mutational networks of escape from transmitted HIV-1 infection"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1710-3693","authenticated-orcid":true,"given":"Elma H.","family":"Akand","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3773-6882","authenticated-orcid":true,"given":"Stephen J.","family":"Maher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9314-2283","authenticated-orcid":true,"given":"John M.","family":"Murray","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2020,12,7]]},"reference":[{"key":"pone.0243391.ref001","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1097\/00002030-200309050-00005","article-title":"Dynamics of HIV viremia and antibody seroconversion in plasma donors: implications for diagnosis and staging of primary HIV infection","volume":"17","author":"EW Fiebig","year":"2003","journal-title":"AIDS"},{"key":"pone.0243391.ref002","doi-asserted-by":"crossref","first-page":"309","DOI":"10.3390\/v4020309","article-title":"Novel Approaches to Inhibit HIV Entry.","volume":"4","author":"CA Didigu","year":"2012","journal-title":"Viruses"},{"key":"pone.0243391.ref003","doi-asserted-by":"crossref","first-page":"E564","DOI":"10.1073\/pnas.1717765115","article-title":"Fitness landscape of the human immunodeficiency virus envelope protein that is targeted by antibodies","volume":"115","author":"RHY Louie","year":"2018","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"pone.0243391.ref004","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0171572","article-title":"Differentiating founder and chronic HIV envelope sequences.","volume":"12","author":"JM Murray","year":"2017","journal-title":"PLoS One."},{"key":"pone.0243391.ref005","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1126\/science.1093137","article-title":"Envelope-Constrained Neutralization-Sensitive HIV-1 After Heterosexual Transmission.","volume":"303","author":"CA Derdeyn","year":"2004","journal-title":"Science"},{"journal-title":"BMC Bioinformatics","article-title":"NGlyAlign: an automated library building tool to align highly divergent HIV envelope sequences.","author":"EH Akand","key":"pone.0243391.ref006"},{"key":"pone.0243391.ref007","doi-asserted-by":"crossref","first-page":"7552","DOI":"10.1073\/pnas.0802203105","article-title":"Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection","volume":"105","author":"BF Keele","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"key":"pone.0243391.ref008","doi-asserted-by":"crossref","first-page":"3556","DOI":"10.1128\/JVI.02132-08","article-title":"Quantitating the multiplicity of infection with human immunodeficiency virus type 1 subtype C reveals a non-poisson distribution of transmitted variants","volume":"83","author":"M-R Abrahams","year":"2009","journal-title":"J Virol"},{"key":"pone.0243391.ref009","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/1742-4690-9-54","article-title":"Application of a case\u2013control study design to investigate genotypic signatures of HIV-1 transmission.","volume":"9","author":"TM Mota","year":"2012","journal-title":"Retrovirology"},{"key":"pone.0243391.ref010","first-page":"III102","volume-title":"Numbering Positions in HIV Relative to HXB2CG.","author":"B Korber","year":"1998"},{"key":"pone.0243391.ref011","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1093\/bioinformatics\/14.9.755","article-title":"Profile hidden Markov models","volume":"14","author":"SR Eddy","year":"1998","journal-title":"Bioinformatics"},{"key":"pone.0243391.ref012","doi-asserted-by":"crossref","first-page":"W3","DOI":"10.1093\/nar\/gkt283","article-title":"DIALIGN at GOBICS\u2014multiple sequence alignment using various sources of external information","volume":"41","author":"L Al Ait","year":"2013","journal-title":"Nucleic Acids Research"},{"key":"pone.0243391.ref013","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1093\/bioinformatics\/15.3.211","article-title":"DIALIGN 2: improvement of the segment-to-segment approach to multiple sequence alignment","volume":"15","author":"B. 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