{"id":{"repo_id":"unsw","oai_identifier":"oai:unsworks.library.unsw.edu.au:1959.4/101822"},"canonical_url":"https://search.dev.ndltd.org/etd/unsw/oai:unsworks.library.unsw.edu.au:1959.4/101822","repository":{"repo_id":"unsw","name":"University of New South Wales","base_url":"https://unsworks.unsw.edu.au/oai/provider"},"display":{"title":"Detection and characterisation of enteroviruses and the gut virome in islet autoimmunity and type 1 diabetes using novel molecular methods","abstract":"Type 1 diabetes (T1D) is a chronic autoimmune condition affecting over 8.4 million individuals globally. Usually preceded by islet autoimmunity (IA), T1D results from a complex interplay between host genetics and environmental factors, with virus infections, especially enteroviruses (EV) identified as a prominent candidate factor. Advances in molecular techniques including next generation sequencing (NGS) have enabled sensitive and high-throughput virus detection, improving on cell culture and serology techniques. There are over 110 human/primate EVs identified, classified within four species (A-D). Elucidation of which subtypes precipitate IA/T1D would inform the design of primary prevention studies. The project aimed to 1) develop a novel method of EV amplification using NGS; 2) optimise capture-based sequencing of viruses in stools of children at-risk of T1D; 3) characterise viruses in stools of participants in the Viruses in the Genetically at Risk (VIGR) and Environmental Determinants of Islet Autoimmunity (ENDIA) Australian longitudinal cohorts; and 4) update our previous systematic review examining the association between EVs and IA/T1D. Near full-length EV was detected in 67% of 113 VIGR stools and 96% of 23 EV prototypes examined. Coxsackievirus (CV)B3, ECHO18/30, and infection with multiple EV subtypes were associated with IA in VIGR stools. Polymorphisms frequently mapped to VP2/VP1 capsid regions in cases and to 2C/VP2/VP3/3A in controls. Children in the VIGR study had 129 differentially abundant gut viruses, with EV-As CVA2/5/6/8/14 and EV-Bs CVB3 and ECHO6/18/30 more abundant in cases. Infants of mothers with T1D enrolled in ENDIA were more likely to have a virus infection, with bocavirus/rotavirus more abundant and CVA6/RV-C/torque teno viruses less abundant. Systematic review of 3,266 publications revealed 60 eligible studies (40 T1D, 9 IA, 11 both) comprising 12,077 individuals. Meta-analysis demonstrated significant associations between EV and IA (odds ratio 2.1; 95% confidence interval 1.3 to 3.3; P=0.002), T1D (8.0; 4.9 to 13.0; P<0.00001); within one month of T1D (16.2; 8.6 to 30.5; P <0.00001). Substantial heterogeneity was observed between studies. These results strengthen the rationale for EV-targeted vaccines for primary prevention of IA/T1D. Future studies will examine virus infection during pregnancy and early life in populations with and without genetic risk for T1D.","abstract_html":"Type 1 diabetes (T1D) is a chronic autoimmune condition affecting over 8.4 million individuals globally. Usually preceded by islet autoimmunity (IA), T1D results from a complex interplay between host genetics and environmental factors, with virus infections, especially enteroviruses (EV) identified as a prominent candidate factor. Advances in molecular techniques including next generation sequencing (NGS) have enabled sensitive and high-throughput virus detection, improving on cell culture and serology techniques. There are over 110 human/primate EVs identified, classified within four species (A-D). Elucidation of which subtypes precipitate IA/T1D would inform the design of primary prevention studies. The project aimed to 1) develop a novel method of EV amplification using NGS; 2) optimise capture-based sequencing of viruses in stools of children at-risk of T1D; 3) characterise viruses in stools of participants in the Viruses in the Genetically at Risk (VIGR) and Environmental Determinants of Islet Autoimmunity (ENDIA) Australian longitudinal cohorts; and 4) update our previous systematic review examining the association between EVs and IA/T1D. Near full-length EV was detected in 67% of 113 VIGR stools and 96% of 23 EV prototypes examined. Coxsackievirus (CV)B3, ECHO18/30, and infection with multiple EV subtypes were associated with IA in VIGR stools. Polymorphisms frequently mapped to VP2/VP1 capsid regions in cases and to 2C/VP2/VP3/3A in controls. Children in the VIGR study had 129 differentially abundant gut viruses, with EV-As CVA2/5/6/8/14 and EV-Bs CVB3 and ECHO6/18/30 more abundant in cases. Infants of mothers with T1D enrolled in ENDIA were more likely to have a virus infection, with bocavirus/rotavirus more abundant and CVA6/RV-C/torque teno viruses less abundant. Systematic review of 3,266 publications revealed 60 eligible studies (40 T1D, 9 IA, 11 both) comprising 12,077 individuals. Meta-analysis demonstrated significant associations between EV and IA (odds ratio 2.1; 95% confidence interval 1.3 to 3.3; P=0.002), T1D (8.0; 4.9 to 13.0; P&lt;0.00001); within one month of T1D (16.2; 8.6 to 30.5; P &lt;0.00001). Substantial heterogeneity was observed between studies. These results strengthen the rationale for EV-targeted vaccines for primary prevention of IA/T1D. Future studies will examine virus infection during pregnancy and early life in populations with and without genetic risk for T1D.","abstract_has_math":false,"creators":["Isaacs, Sonia"],"institution":"UNSW, Sydney","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2024,"date_issued":"2024","date_published":"2024","updated_at":"2026-07-24T05:32:27Z","subjects":["enterovirus","virome","type 1 diabetes","islet autoimmunity","next generation sequencing","VIGR","ENDIA","virus detection","Illumina","VirCapSeq-VERT","SNP","Meta-Analysis","anzsrc-for: 3207 Medical microbiology","anzsrc-for: 310706 Virology","anzsrc-for: 320208 Endocrinology","anzsrc-for: 3213 Paediatrics"],"languages":["en"],"rights":["open access","CC BY 4.0","free_to_read"],"rights_urls":["https://purl.org/coar/access_right/c_abf2","https://creativecommons.org/licenses/by/4.0/"],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["https://doi.org/10.26190/unsworks/25526"],"render_values":[{"text":"https://doi.org/10.26190/unsworks/25526","href":"https://doi.org/10.26190/unsworks/25526","code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/1959.4/101822","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Isaacs, Sonia"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2024"]},{"key":"dc:publisher","label":"Institution","values":["UNSW, Sydney"]},{"key":"dc:type","label":"Dc Type","values":["doctoral thesis","http://purl.org/coar/resource_type/c_db06"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["enterovirus","virome","type 1 diabetes","islet autoimmunity","next generation sequencing","VIGR","ENDIA","virus detection","Illumina","VirCapSeq-VERT","SNP","Meta-Analysis","anzsrc-for: 3207 Medical microbiology","anzsrc-for: 310706 Virology","anzsrc-for: 320208 Endocrinology","anzsrc-for: 3213 Paediatrics"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["open access","https://purl.org/coar/access_right/c_abf2","CC BY 4.0","https://creativecommons.org/licenses/by/4.0/","free_to_read"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/1959.4/101822","https://unsworks.unsw.edu.au/bitstreams/0397e604-45a9-474c-9666-ce77871081bf/download","https://doi.org/10.26190/unsworks/25526"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Type 1 diabetes (T1D) is a chronic autoimmune condition affecting over 8.4 million individuals globally. Usually preceded by islet autoimmunity (IA), T1D results from a complex interplay between host genetics and environmental factors, with virus infections, especially enteroviruses (EV) identified as a prominent candidate factor. Advances in molecular techniques including next generation sequencing (NGS) have enabled sensitive and high-throughput virus detection, improving on cell culture and serology techniques. There are over 110 human/primate EVs identified, classified within four species (A-D). Elucidation of which subtypes precipitate IA/T1D would inform the design of primary prevention studies. The project aimed to 1) develop a novel method of EV amplification using NGS; 2) optimise capture-based sequencing of viruses in stools of children at-risk of T1D; 3) characterise viruses in stools of participants in the Viruses in the Genetically at Risk (VIGR) and Environmental Determinants of Islet Autoimmunity (ENDIA) Australian longitudinal cohorts; and 4) update our previous systematic review examining the association between EVs and IA/T1D. Near full-length EV was detected in 67% of 113 VIGR stools and 96% of 23 EV prototypes examined. Coxsackievirus (CV)B3, ECHO18/30, and infection with multiple EV subtypes were associated with IA in VIGR stools. Polymorphisms frequently mapped to VP2/VP1 capsid regions in cases and to 2C/VP2/VP3/3A in controls. Children in the VIGR study had 129 differentially abundant gut viruses, with EV-As CVA2/5/6/8/14 and EV-Bs CVB3 and ECHO6/18/30 more abundant in cases. Infants of mothers with T1D enrolled in ENDIA were more likely to have a virus infection, with bocavirus/rotavirus more abundant and CVA6/RV-C/torque teno viruses less abundant. Systematic review of 3,266 publications revealed 60 eligible studies (40 T1D, 9 IA, 11 both) comprising 12,077 individuals. Meta-analysis demonstrated significant associations between EV and IA (odds ratio 2.1; 95% confidence interval 1.3 to 3.3; P=0.002), T1D (8.0; 4.9 to 13.0; P<0.00001); within one month of T1D (16.2; 8.6 to 30.5; P <0.00001). Substantial heterogeneity was observed between studies. These results strengthen the rationale for EV-targeted vaccines for primary prevention of IA/T1D. Future studies will examine virus infection during pregnancy and early life in populations with and without genetic risk for T1D."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Detection and characterisation of enteroviruses and the gut virome in islet autoimmunity and type 1 diabetes using novel molecular methods"]}]}],"canonical_facts":{"dc:creator":["Isaacs, Sonia"],"dc:date":["2024"],"dc:description":["Type 1 diabetes (T1D) is a chronic autoimmune condition affecting over 8.4 million individuals globally. Usually preceded by islet autoimmunity (IA), T1D results from a complex interplay between host genetics and environmental factors, with virus infections, especially enteroviruses (EV) identified as a prominent candidate factor. Advances in molecular techniques including next generation sequencing (NGS) have enabled sensitive and high-throughput virus detection, improving on cell culture and serology techniques. There are over 110 human/primate EVs identified, classified within four species (A-D). Elucidation of which subtypes precipitate IA/T1D would inform the design of primary prevention studies. The project aimed to 1) develop a novel method of EV amplification using NGS; 2) optimise capture-based sequencing of viruses in stools of children at-risk of T1D; 3) characterise viruses in stools of participants in the Viruses in the Genetically at Risk (VIGR) and Environmental Determinants of Islet Autoimmunity (ENDIA) Australian longitudinal cohorts; and 4) update our previous systematic review examining the association between EVs and IA/T1D. Near full-length EV was detected in 67% of 113 VIGR stools and 96% of 23 EV prototypes examined. Coxsackievirus (CV)B3, ECHO18/30, and infection with multiple EV subtypes were associated with IA in VIGR stools. Polymorphisms frequently mapped to VP2/VP1 capsid regions in cases and to 2C/VP2/VP3/3A in controls. Children in the VIGR study had 129 differentially abundant gut viruses, with EV-As CVA2/5/6/8/14 and EV-Bs CVB3 and ECHO6/18/30 more abundant in cases. Infants of mothers with T1D enrolled in ENDIA were more likely to have a virus infection, with bocavirus/rotavirus more abundant and CVA6/RV-C/torque teno viruses less abundant. Systematic review of 3,266 publications revealed 60 eligible studies (40 T1D, 9 IA, 11 both) comprising 12,077 individuals. Meta-analysis demonstrated significant associations between EV and IA (odds ratio 2.1; 95% confidence interval 1.3 to 3.3; P=0.002), T1D (8.0; 4.9 to 13.0; P<0.00001); within one month of T1D (16.2; 8.6 to 30.5; P <0.00001). Substantial heterogeneity was observed between studies. These results strengthen the rationale for EV-targeted vaccines for primary prevention of IA/T1D. Future studies will examine virus infection during pregnancy and early life in populations with and without genetic risk for T1D."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/1959.4/101822","https://unsworks.unsw.edu.au/bitstreams/0397e604-45a9-474c-9666-ce77871081bf/download","https://doi.org/10.26190/unsworks/25526"],"dc:language":["en"],"dc:publisher":["UNSW, Sydney"],"dc:rights":["open access","https://purl.org/coar/access_right/c_abf2","CC BY 4.0","https://creativecommons.org/licenses/by/4.0/","free_to_read"],"dc:subject":["enterovirus","virome","type 1 diabetes","islet autoimmunity","next generation sequencing","VIGR","ENDIA","virus detection","Illumina","VirCapSeq-VERT","SNP","Meta-Analysis","anzsrc-for: 3207 Medical microbiology","anzsrc-for: 310706 Virology","anzsrc-for: 320208 Endocrinology","anzsrc-for: 3213 Paediatrics"],"dc:title":["Detection and characterisation of enteroviruses and the gut virome in islet autoimmunity and type 1 diabetes using novel molecular methods"],"dc:type":["doctoral thesis","http://purl.org/coar/resource_type/c_db06"]},"updated_at":"2026-07-24T05:32:27Z"}