APOBEC3: Friend or Foe in Human Papillomavirus Infection and Oncogenesis?

APOBEC3: Friend or Foe in Human Papillomavirus Infection and Oncogenesis?
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DOI:
10.1146/annurev-virology-092920-030354
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发表时间:
2022-09-29
影响因子:
11.3
通讯作者:
--
中科院分区:
医学2区
文献类型:
--
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人乳头瘤病毒(HPV)感染是多种人类癌症的病原体,包括宫颈癌和头颈癌。在这些HPV阳性肿瘤中,体细胞突变是由DNA突变体的异常激活引起的,例如胞苷脱氨酶的载脂蛋白B mRNA编辑酶催化多肽样3(APOBEC 3)家族的成员。APOBEC3蛋白最值得注意的是它们对各种病毒的限制,包括抗HPV活性。然而,APOBEC3蛋白在HPV诱导的癌症进展中的潜在作用最近引起了广泛关注。正在进行的研究源于观察到APOBEC3表达升高是由HPV癌基因表达驱动的,并且APOBEC3活性可能是HPV阳性癌症中体细胞诱变的重要贡献者。本文就APOBEC3蛋白及其在HPV感染和HPV致瘤中的作用的研究进展作一综述。此外,我们还讨论了我们对病毒相关癌症中APOBEC3的理解中的关键差距和未回答的问题。
Human papillomavirus (HPV) infection is a causative agent of multiple human cancers, including cervical and head and neck cancers. In these HPV-positive tumors, somatic mutations are caused by aberrant activation of DNA mutators such as members of the apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) family of cytidine deaminases. APOBEC3 proteins are most notable for their restriction of various viruses, including anti-HPV activity. However, the potential role of APOBEC3 proteins in HPV-induced cancer progression has recently garnered significant attention. Ongoing research stems from the observations that elevated APOBEC3 expression is driven by HPV oncogene expression and that APOBEC3 activity is likely a significant contributor to somatic mutagenesis in HPV-positive cancers. This review focuses on recent advances in the study of APOBEC3 proteins and their roles in HPV infection and HPV-driven oncogenesis. Further, we discuss critical gaps and unanswered questions in our understanding of APOBEC3 in virus-associated cancers.
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