Abstract
The apolipoprotein B messenger RNA-editing, enzyme-catalytic, polypeptide-like 3 (APOBEC3) family of cytidine deaminases plays an important role in the innate immune response to viral infections by editing viral genomes. However, the cytidine deaminase activity of APOBEC3 enzymes also induces somatic mutations in host genomes, which may drive cancer progression. Recent studies of human papillomavirus (HPV) infection and disease outcome highlight this duality. HPV infection is potently inhibited by one family member, APOBEC3A. Expression of APOBEC3A and APOBEC3B is highly elevated by the HPV oncoproteins E6 and E7 during persistent virus infection and disease progression. Furthermore, there is a high prevalence of APOBEC3A and APOBEC3B mutation signatures in HPV-associated cancers. These findings suggest that induction of an APOBEC3-mediated antiviral response during HPV infection may inadvertently contribute to cancer mutagenesis and virus evolution. Here, we discuss current understanding of APOBEC3A and APOBEC3B biology in HPV restriction, evolution, and associated cancer mutagenesis.
Highlights
The family members of apolipoprotein B messenger RNA-editing, enzyme-catalytic, polypeptide-like 3 (APOBEC3; A3) are DNA cytidine deaminases that remove the amino group from a cytosine, converting it to uracil
Several studies from our and other groups have revealed a broader range of viruses restricted by A3A and A3B: human immunodeficiency virus 1 (HIV-1) [8,9,10], parvovirus [11,12,13], herpesvirus [14,15], hepatitis B virus (HBV) [16,17], and human papillomavirus (HPV) [18,19,20] (Table 1)
A3 deaminase activity is causally associated with helical domain hotspot mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene, which are more prevalent in HPV-positive cancers when compared to HPV-negative cancers [131]
Summary
The family members of apolipoprotein B messenger RNA-editing, enzyme-catalytic, polypeptide-like 3 (APOBEC3; A3) are DNA cytidine deaminases that remove the amino group from a cytosine, converting it to uracil. Recent studies have identified additional important roles for these family members in diverse cellular processes, including (1) promoting catabolism of foreign DNA [21,22]; (2) editing of mRNA transcripts [23,24,25]; and (3) promoting host genome mutations and DNA damage that may contribute to cellular transformation [26,27,28,29,30,31,32,33,34]
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