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The prevalence of HTLV-1 infection varies greatly from region to region, and available epidemiological data support the notion that even among regions of similarly high prevalence of HTLV-1 infection, such as Japan, South America, or Central Australia, the incidence of each associated disease may vary drastically. Here, we critically review evidence supporting a high incidence of ATLL in Japan, in contrast to a high incidence of HAM\/TSP in South America, and a low incidence of both diseases in Central Australia, where other HTLV-1 inflammatory diseases are common. We further aim to explore these singularities through the lens of HTLV-1 genetic diversity. Different genetic clades are geographically restricted, such as HTLV-1a-Jpn and HTLV-1a-TC in Japan, HTLV-1a-TC in South America, HTLV-1a-TC and HTLV-1b in Africa, and HTLV-1c in Australo-Melanesia. We analyze potential correlations between HTLV-1 genotypes and disease outcomes while also discussing the interaction with other genetic or environmental factors that may contribute to these differences (e.g., host genetic background, age of infection, routes of transmission, or environmental factors). This perspective raises important questions about the unique properties of the different HTLV-1 genotypes and how they may reshape our understanding of HTLV-1 pathophysiology on both molecular and epidemiological levels.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.00601-25","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T09:00:13Z","timestamp":1751878813000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["Untangling the causes of geographical disparities in the clinical outcome of HTLV-1 infection: a critical perspective on the contribution of viral genetic diversity"],"prefix":"10.1128","volume":"99","author":[{"given":"Thomas","family":"Duchateau","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04zmssz18","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre International de Recherche en Infectiologie, Retroviral Oncogenesis team, Inserm U1111 - Universit\u00e9 Claude Bernard Lyon 1, CNRS, UMR5308, \u00c9cole Normale Sup\u00e9rieure de Lyon, Universit\u00e9 Lyon","place":["Lyon, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe V.","family":"Afonso","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05f82e368","id-type":"ROR","asserted-by":"publisher"}],"name":"Unit\u00e9 \u00c9pid\u00e9miologie des Virus Oncog\u00e8nes, Institut Pasteur, Universit\u00e9 Paris Cit\u00e9","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0973-0777","authenticated-orcid":true,"given":"Chlo\u00e9","family":"Journo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04zmssz18","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre International de Recherche en Infectiologie, Retroviral Oncogenesis team, Inserm U1111 - Universit\u00e9 Claude Bernard Lyon 1, CNRS, UMR5308, \u00c9cole Normale Sup\u00e9rieure de Lyon, Universit\u00e9 Lyon","place":["Lyon, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.77.12.7415"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.10.6476"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910300302"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(85)92734-5"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910320313"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.1890260402"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V50.3.481.481"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00063-09"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(90)92896-P"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(19)30402-5"},{"key":"e_1_3_2_12_2","first-page":"1","article-title":"Ocular manifestations in patients infected with human T-lymphotropic virus type I","volume":"33","author":"Ohba N","year":"1989","unstructured":"Ohba N, Matsumoto M, Sameshima M, Kabayama Y, Nakao K, Unoki K, Uehara F, Kawano K, Maruyama I, Osame M. 1989. 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