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They restrict viral replication by deaminating cytosines to uracil in viral DNA during replication, producing hypermutations that reduce viral fitness and can inactivate the virus. APOBEC3 activity also suppresses multiple DNA tumour virus families, including herpesviruses, papillomaviruses, and hepadnaviruses. Because DNA virus infections can drive cancer, APOBEC3 mutational signatures in diverse human tumours indicate a dual role in immunity and carcinogenesis. This review explains their mechanisms, viral countermeasures, and implications for targeted therapies.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/the-intricate-interplay-between-apobec3-proteins-and-dna-tumour-viruses/331952/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/the-intricate-interplay-between-apobec3-proteins-and-dna-tumour-viruses/331952.png","ImageObject",300,407,{"name":92,"@type":93},"Lucas Martin","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-23","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"How do APOBEC3 proteins restrict DNA tumour virus replication?","Question",{"text":112,"@type":113},"They deaminate cytosine to uracil in viral DNA during replication, causing hypermutation of the viral genome that reduces viral fitness and can inactivate the virus.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which DNA tumour virus families are mentioned as being inhibited by APOBEC3 proteins?",{"text":117,"@type":113},"The review highlights herpesviruses, papillomaviruses, and hepadnaviruses as virus groups whose replication can be restricted by APOBEC3 proteins.",{"name":119,"@type":110,"acceptedAnswer":120},"Why are APOBEC3 proteins considered to have a dual role in cancer development?",{"text":121,"@type":113},"On one hand, APOBEC3 contributes to innate immune control of viral infections; on the other, persistent infections and APOBEC3-associated mutational signatures can support pathogenesis and tumour progression.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},331952,1790196455,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":29,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":56,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144,"preview_page_count":4},8796095360427,"https://ap-avatar.wpscdn.com/davatar_994ba38a5ba835b3df7d355c54d3ed8d","pathogens   \nReview  \nThe Intricate Interplay between APOBEC3 Proteins and DNA Tumour Viruses  \nNika Lovšin 1, Bhavani Gangupam 2 and Martina Bergant Marušiˇc 2, *  \nCitation: Lovšin, N.; Gangupam, B.; Bergant Marušiˇc, M. The Intricate Interplay between APOBEC3 Proteins and DNA Tumour Viruses. Pathogens 2024, 13, 187. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/pathogens13030187](10.3390/pathogens13030187)  \nAcademic Editor: Ramona Gabriela Ursu  \nReceived: 31 January 2024  \nRevised: 16 February 2024  \nAccepted: 17 February 2024  \nPublished: 20 February 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Faculty of Pharmacy, University of Ljubljana, Aškerˇceva 7, 1000 Ljubljana, Slovenia;  \nmarija.nika.lovsin@ffa.uni-lj.si  \n2 Laboratory for Environmental and Life Sciences, University of Nova Gorica, Vipavska 13, 5000 Nova Gorica, Slovenia; [bhavani.gangupam@ung.si](bhavani.gangupam@ung.si)  \n* [Correspondence: martina.bergant@ung.si](Correspondence: martina.bergant@ung.si)  \nAbstract: APOBEC3 proteins are cytidine deaminases that play a crucial role in the innate immune response against viruses, including DNA viruses. Their main mechanism for restricting viral replication is the deamination of cytosine to uracil in viral DNA during replication. This process leads to hypermutation of the viral genome, resulting in loss of viral fitness and, in many cases, inactivation of the virus. APOBEC3 proteins inhibit the replication of a number of DNA tumour viruses, including herpesviruses, papillomaviruses and hepadnaviruses. Different APOBEC3s restrict the replication of different virus families in different ways and this restriction is not limited to one APOBEC3 . Infection with DNA viruses often leads to the development and progression of cancer. APOBEC3 mutational signatures have been detected in various cancers, indicating the importance of APOBEC3sin carcinogenesis. Inhibition of DNA viruses by APOBEC3 proteins appears to play a dual role in this process. On the one hand, it is an essential component of the innate immune response to viral infections, and, on the other hand, it contributes to the pathogenesis of persistent viral infections and the progression of cancer. The current review examines the complex interplay between APOBEC3 proteins and DNA viruses and sheds light on the mechanisms of action, viral countermeasures and the impact on carcinogenesis. Deciphering the current issues in the interaction of APOBEC/DNA viruses should enable the development of new targeted cancer therapies.  \nKeywords: APOBEC; DNA tumour viruses; viral restriction; tumorigenesis; DNA editing  \n1. Introduction  \nAPOBEC3 (A3) proteins are cytidine deaminases that belong to the family of apolipoprotein B mRNA editing complex polypeptide 1–like (APOBEC) enzymes. Originally discovered as antiviral factors in HIV-1 infection [1], APOBEC3s were later identified as general antiviral factors that block the replication of various viruses and retrotransposons [2–4]. Intriguingly, recent broad genomic studies have uncovered APOBECs as an important source of somatic mutations in various cancers, including breast, ovarian, bladder, prostate, pancreatic, kidney, and cervical cancers [4] and thus as a possible mechanism contributing to cell transformation and cancer development.  \nThe APOBEC3 genes belong to the interferon-stimulated genes (ISGs) . During viral infections, the expression of interferons (IFNs) and cytokines/chemokines is controlled by cytosolic nucleic acid sensors that recognize foreign RNA and DNA [5] . When the innate immune system responds to viral infections, particularly at mucosal sites where sentinel cell","cbCaiuMVvbv0UVWG","https://ap.wps.com/l/cbCaiuMVvbv0UVWG","pdf",804054,"English","# Abstract\n# Introduction\n## APOBEC3 as innate antiviral enzymes\n## APOBEC3 activity and DNA virus replication\n## Oncogenic DNA tumour viruses and cancer risk\n## Viral strategies and APOBEC3 evolutionary footprints","[{\"question\":\"How do APOBEC3 proteins restrict DNA tumour virus replication?\",\"answer\":\"They deaminate cytosine to uracil in viral DNA during replication, causing hypermutation of the viral genome that reduces viral fitness and can inactivate the virus.\"},{\"question\":\"Which DNA tumour virus families are mentioned as being inhibited by APOBEC3 proteins?\",\"answer\":\"The review highlights herpesviruses, papillomaviruses, and hepadnaviruses as virus groups whose replication can be restricted by APOBEC3 proteins.\"},{\"question\":\"Why are APOBEC3 proteins considered to have a dual role in cancer development?\",\"answer\":\"On one hand, APOBEC3 contributes to innate immune control of viral infections; on the other, persistent infections and APOBEC3-associated mutational signatures can support pathogenesis and tumour progression.\"}]","The Intricate Interplay between APOBEC3 Proteins and DNA Tumour Viruses | PDF",1789995954,48]