{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T16:21:13Z","timestamp":1783959673671,"version":"3.55.0"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T00:00:00Z","timestamp":1762992000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Human Immunodeficiency Virus type 1 (HIV-1) cross-regional transmission poses a critical challenge in China, particularly in high-mobility metropolitan centers. This study aimed to characterize the transmission dynamics between Hangzhou\u2014a megacity with 11.9 million residents (42% migrants)\u2014and other Chinese regions using molecular epidemiology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed 4,249 Hangzhou-derived and 50,898 non-Hangzhou HIV-1 pol sequences. Molecular transmission network analysis was used to identify transmission clusters, and phylogenetic and Bayesian analyses were conducted to explore lineage characteristics, origins, and expansion of major clusters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Molecular transmission network analysis identified 3,317 clusters, incorporating 43.5% (1,848\/4,249) of Hangzhou sequences and 32.4% (16,511\/50,898) of non-Hangzhou sequences. Crucially, 276 mixed-origin clusters bridged regions, comprising 1,222 (28.8%) Hangzhou and 8,954 (17.6%) non-Hangzhou individuals. Cross-regional connectivity was dominated by Shenzhen (48.1% of 46,962 edges), followed by Beijing (16.5%) and Guangzhou (7.9%). Multivariable regression revealed significantly higher odds of cross-regional connection for males versus females (aOR\u202f=\u202f1.376, CI: 1.011\u20131.869,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.043), homosexual transmission (aOR\u202f=\u202f1.28, CI: 1.057\u20131.550,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.009), non-residents (aOR\u202f=\u202f1.207, CI: 1.040\u20131.402,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.014), and first CD4\u202f+\u202fT-cell count of 200\u2013500 cells\/uL (aOR\u202f=\u202f1.348, CI: 1.057\u20131.718,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.016). For subtypes, CRF07_BC and URF (CRF07_BC\/CRF01_AE) demonstrated significant cross-regional spread versus other subtypes (aOR\u202f=\u202f0.163\u20130.508,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001). Phylogenetic analysis of all Hangzhou CRF07_BC sequences identified two distinct lineages. Within the largest transmission CRF07_BC cluster, 99.5% of cross-regionally linked Hangzhou sequences (558\/561) belonged to Lineage 1 indicating lineage 1 driving cross-regional spread. Bayesian dating indicated major URF clusters (HZC1-3, NHZ) originated between 2014 and 2020 (evolutionary rate: 1.73\u202f\u00d7\u202f10\n                      <jats:sup>\u22123<\/jats:sup>\n                      subs\/site\/year).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings identify key transmission routes connecting Hangzhou to economically developed regions and highlight CRF07_BC\/URF strains and mobility as critical drivers. Targeted interventions disrupting these high-risk pathways are urgently needed to reduce regional HIV spread.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2025.1682213","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T06:30:18Z","timestamp":1763015418000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Spatiotemporal dynamics of HIV-1 transmission networks in a major migration hub: integrated phylogenetic and molecular evidence"],"prefix":"10.3389","volume":"16","author":[{"given":"Min","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junfang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhou","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingliang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sisheng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojuan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,13]]},"reference":[{"key":"ref9","doi-asserted-by":"publisher","first-page":"61","DOI":"10.3389\/fmicb.2020.00061","article-title":"Cross-continental dispersal of major HIV-1 CRF01_AE clusters in China","volume":"11","author":"An","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref13","year":"2018"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1458","DOI":"10.1111\/j.1365-3156.2010.02647.x","article-title":"Linking migration, mobility and HIV","volume":"15","author":"Deane","year":"2010","journal-title":"Trop. Med. Int. Health"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"824178","DOI":"10.3389\/fimmu.2022.824178","article-title":"Spatiotemporal patterns of CRF07_BC in China: a population-based study of the HIV strain with the highest infection rates","volume":"13","author":"Gan","year":"2022","journal-title":"Front. Immunol."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1919","DOI":"10.1080\/22221751.2021.1978822","article-title":"HIV-1 CRF07_BC transmission dynamics in China: two decades of national molecular surveillance","volume":"10","author":"Ge","year":"2021","journal-title":"Emerg Microbes Infect"},{"key":"ref4","year":"2023"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.46234\/ccdcw2021.249","article-title":"Research progress in the epidemiology of HIV\/AIDS in China","volume":"3","author":"He","year":"2021","journal-title":"CDC Wkly."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.3760\/cma.j.cn112338-20220424-00339","article-title":"Analysis of HIV transmission hotspots and characteristics of cross-regional transmission in Guangxi Zhuang autonomous region based on molecular network","volume":"43","author":"Jiang","year":"2022","journal-title":"Zhonghua Liu Xing Bing Xue Za Zhi"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1812","DOI":"10.1093\/molbev\/msy016","article-title":"HIV-TRACE (TRAnsmission cluster engine): a tool for large scale molecular epidemiology of HIV-1 and other rapidly evolving pathogens","volume":"35","author":"Kosakovsky Pond","year":"2018","journal-title":"Mol. Biol. Evol."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"e28973","DOI":"10.1002\/jmv.28973","article-title":"Characteristics of genotype, drug resistance, and molecular transmission network among newly diagnosed HIV-1 infections in Shenzhen, China","volume":"95","author":"Li","year":"2023","journal-title":"J. Med. Virol."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1093\/bioinformatics\/bti079","article-title":"HyPhy: hypothesis testing using phylogenies","volume":"21","author":"Pond","year":"2005","journal-title":"Bioinformatics"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1093\/sysbio\/syy032","article-title":"Posterior summarization in Bayesian Phylogenetics using tracer 1.7","volume":"67","author":"Rambaut","year":"2018","journal-title":"Syst. Biol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"ofz135","DOI":"10.1093\/ofid\/ofz135","article-title":"National and international dimensions of human immunodeficiency virus-1 sequence clusters in a northern California clinical cohort","volume":"6","author":"Rhee","year":"2019","journal-title":"Open Forum Infect. Dis."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"16046","DOI":"10.1038\/s41598-018-33996-6","article-title":"Impact of worker emigration on HIV epidemics in labour export areas: a molecular epidemiology investigation in Guangyuan, China","volume":"8","author":"Su","year":"2018","journal-title":"Sci. Rep."},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1093\/ve\/vey016","article-title":"Bayesian phylogenetic and phylodynamic data integration using BEAST 1.10","volume":"4","author":"Suchard","year":"2018","journal-title":"Virus Evol."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1186\/s12985-023-02112-0","article-title":"HIV-1 molecular transmission network and drug resistance in Chongqing, China, among men who have sex with men (2018-2021)","volume":"20","author":"Tan","year":"2023","journal-title":"Virol. J."},{"key":"ref1","year":"2024"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.46234\/ccdcw2024.252","article-title":"National and regional molecular epidemiology of HIV-1 - China, 2004-2023","volume":"6","author":"Wang","year":"2024","journal-title":"China CDC Wkly"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"13892","DOI":"10.1038\/s41598-017-14108-2","article-title":"Highlighting the crucial role of Hangzhou in HIV-1 transmission among men who have sex with men in Zhejiang, China","volume":"7","author":"Zhang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"2373105","DOI":"10.1080\/21505594.2024.2373105","article-title":"Prevalence and transmission of pretreatment drug resistance in people living with HIV-1 in Shanghai China, 2017-2021","volume":"15","author":"Zhang","year":"2024","journal-title":"Virulence"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"28703","DOI":"10.1038\/srep28703","article-title":"The dynamics of the HIV epidemic among men who have sex with men (MSM) from 2005 to 2012 in Shenzhen, China","volume":"6","author":"Zhao","year":"2016","journal-title":"Sci. Rep."},{"key":"ref5","year":"2022"}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2025.1682213\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T06:30:19Z","timestamp":1763015419000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2025.1682213\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,13]]},"references-count":22,"alternative-id":["10.3389\/fmicb.2025.1682213"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2025.1682213","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,13]]},"article-number":"1682213"}}