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

Overview

Journal Annu Rev Virol

Publisher Annual Reviews

Specialty Microbiology

Date 2022 Jun 7

PMID 35671565

Authors

Cody J Warren

Mario L Santiago

Dohun Pyeon

Affiliations

Soon will be listed here.

Abstract

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 messenger RNA-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.

Citing Articles

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References

Suspene R, Guetard D, Henry M, Sommer P, Wain-Hobson S, Vartanian J . Extensive editing of both hepatitis B virus DNA strands by APOBEC3 cytidine deaminases in vitro and in vivo. Proc Natl Acad Sci U S A. 2005; 102(23):8321-6. PMC: 1149401. DOI: 10.1073/pnas.0408223102. View

Shapiro M, Krug L, MacCarthy T . Mutational pressure by host APOBEC3s more strongly affects genes expressed early in the lytic phase of herpes simplex virus-1 (HSV-1) and human polyomavirus (HPyV) infection. PLoS Pathog. 2021; 17(4):e1009560. PMC: 8115780. DOI: 10.1371/journal.ppat.1009560. View

Hedegaard J, Lamy P, Nordentoft I, Algaba F, Hoyer S, Ulhoi B . Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma. Cancer Cell. 2016; 30(1):27-42. DOI: 10.1016/j.ccell.2016.05.004. View

Halemano K, Guo K, Heilman K, Barrett B, Smith D, Hasenkrug K . Immunoglobulin somatic hypermutation by APOBEC3/Rfv3 during retroviral infection. Proc Natl Acad Sci U S A. 2014; 111(21):7759-64. PMC: 4040588. DOI: 10.1073/pnas.1403361111. View

Lindskrog S, Prip F, Lamy P, Taber A, Groeneveld C, Birkenkamp-Demtroder K . An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer. Nat Commun. 2021; 12(1):2301. PMC: 8052448. DOI: 10.1038/s41467-021-22465-w. View

Lawrence M, Stojanov P, Polak P, Kryukov G, Cibulskis K, Sivachenko A . Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature. 2013; 499(7457):214-218. PMC: 3919509. DOI: 10.1038/nature12213. View

DeCarlo C, Severini A, Edler L, Escott N, Lambert P, Ulanova M . IFN-κ, a novel type I IFN, is undetectable in HPV-positive human cervical keratinocytes. Lab Invest. 2010; 90(10):1482-91. DOI: 10.1038/labinvest.2010.95. View

Wang Z, Wakae K, Kitamura K, Aoyama S, Liu G, Koura M . APOBEC3 deaminases induce hypermutation in human papillomavirus 16 DNA upon beta interferon stimulation. J Virol. 2013; 88(2):1308-17. PMC: 3911654. DOI: 10.1128/JVI.03091-13. View

Van Doorslaer K . Evolution of the papillomaviridae. Virology. 2013; 445(1-2):11-20. DOI: 10.1016/j.virol.2013.05.012. View

10.

Qi G, Xiong H, Zhou C . APOBEC3 deletion polymorphism is associated with epithelial ovarian cancer risk among Chinese women. Tumour Biol. 2014; 35(6):5723-6. DOI: 10.1007/s13277-014-1758-7. View

11.

Nik-Zainal S, Wedge D, Alexandrov L, Petljak M, Butler A, Bolli N . Association of a germline copy number polymorphism of APOBEC3A and APOBEC3B with burden of putative APOBEC-dependent mutations in breast cancer. Nat Genet. 2014; 46(5):487-91. PMC: 4137149. DOI: 10.1038/ng.2955. View

12.

Roberts S, Lawrence M, Klimczak L, Grimm S, Fargo D, Stojanov P . An APOBEC cytidine deaminase mutagenesis pattern is widespread in human cancers. Nat Genet. 2013; 45(9):970-6. PMC: 3789062. DOI: 10.1038/ng.2702. View

13.

Sheehy A, Gaddis N, Choi J, Malim M . Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature. 2002; 418(6898):646-50. DOI: 10.1038/nature00939. View

14.

Suspene R, Aynaud M, Koch S, Pasdeloup D, Labetoulle M, Gaertner B . Genetic editing of herpes simplex virus 1 and Epstein-Barr herpesvirus genomes by human APOBEC3 cytidine deaminases in culture and in vivo. J Virol. 2011; 85(15):7594-602. PMC: 3147940. DOI: 10.1128/JVI.00290-11. View

15.

Strickland S, Brimer N, Lyons C, Vande Pol S . Human Papillomavirus E6 interaction with cellular PDZ domain proteins modulates YAP nuclear localization. Virology. 2018; 516:127-138. PMC: 5826896. DOI: 10.1016/j.virol.2018.01.003. View

16.

Stadler D, Kachele M, Jones A, Hess J, Urban C, Schneider J . Interferon-induced degradation of the persistent hepatitis B virus cccDNA form depends on ISG20. EMBO Rep. 2021; 22(6):e49568. PMC: 8183418. DOI: 10.15252/embr.201949568. View

17.

Henderson S, Chakravarthy A, Su X, Boshoff C, Fenton T . APOBEC-mediated cytosine deamination links PIK3CA helical domain mutations to human papillomavirus-driven tumor development. Cell Rep. 2014; 7(6):1833-41. DOI: 10.1016/j.celrep.2014.05.012. View

18.

Granadillo Rodriguez M, Flath B, Chelico L . The interesting relationship between APOBEC3 deoxycytidine deaminases and cancer: a long road ahead. Open Biol. 2020; 10(12):200188. PMC: 7776566. DOI: 10.1098/rsob.200188. View

19.

Harris R, Bishop K, Sheehy A, Craig H, Petersen-Mahrt S, Watt I . DNA deamination mediates innate immunity to retroviral infection. Cell. 2003; 113(6):803-9. DOI: 10.1016/s0092-8674(03)00423-9. View

20.

Kukimoto I, Mori S, Aoyama S, Wakae K, Muramatsu M, Kondo K . Hypermutation in the E2 gene of human papillomavirus type 16 in cervical intraepithelial neoplasia. J Med Virol. 2015; 87(10):1754-60. DOI: 10.1002/jmv.24215. View