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.
Interferon induces morphologic reversion with elimination of extrachromosomal viral genomes in bovine papillomavirus-transformed mouse cells
Destabilization of the RB tumor suppressor protein and stabilization of p53 contribute to HPV type 16 E7-induced apoptosis
Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts
A new phylogenetic marker, apolipoprotein B, provides compelling evidence for eutherian relationships
Vif overcomes the innate antiviral activity of APOBEC3G by promoting its degradation in the ubiquitin-proteasome pathway.
Repression of the human papillomavirus E6 gene initiates p53-dependent, telomerase-independent senescence and apoptosis in HeLa cervical carcinoma cells
Selective assembly of HIV-1 Vif-Cul5-ElonginB-ElonginC E3 ubiquitin ligase complex through a novel SOCS box and upstream cysteines
Extensive editing of both hepatitis B virus DNA strands by APOBEC3 cytidine deaminases in vitro and in vivo
Production of infectious human papillomavirus independently of viral replication and epithelial cell differentiation
Induction of APOBEC3 family proteins, a defensive maneuver underlying interferon-induced anti-HIV-1 activity
Selection of cervical keratinocytes containing integrated HPV16 associates with episome loss and an endogenous antiviral response
Interferon-inducible expression of APOBEC3 editing enzymes in human hepatocytes and inhibition of hepatitis B virus replication
Inhibition of cervical cancer cell growth in vitro and in vivo with lentiviral-vector delivered short hairpin RNA targeting human papillomavirus E6 and E7 oncogenes
Interferon-beta treatment of cervical keratinocytes naturally infected with human papillomavirus 16 episomes promotes rapid reduction in episome numbers and emergence of latent integrants
Evolutionarily conserved and non-conserved retrovirus restriction activities of artiodactyl APOBEC3F proteins
APOBEC3F can inhibit the accumulation of HIV-1 reverse transcription products in the absence of hypermutation. Comparisons with APOBEC3G
Human papillomavirus E7 repression in cervical carcinoma cells initiates a transcriptional cascade driven by the retinoblastoma family, resulting in senescence
Virion-associated uracil DNA glycosylase-2 and apurinic/apyrimidinic endonuclease are involved in the degradation of APOBEC3G-edited nascent HIV-1 DNA
The intrinsic antiretroviral factor APOBEC3B contains two enzymatically active cytidine deaminase domains
Antisense targeting human papillomavirus type 16 E6 and E7 genes contributes to apoptosis and senescence in SiHa cervical carcinoma cells
Human papillomavirus type 16 E7 oncoprotein associates with the cullin 2 ubiquitin ligase complex, which contributes to degradation of the retinoblastoma tumor suppressor
An increase in DNA double-strand breaks, induced by Ku70 depletion, is associated with human papillomavirus 16 episome loss and de novo viral integration events
Effects of point mutations in the cytidine deaminase domains of APOBEC3B on replication and hypermutation of hepatitis B virus in vitro
Equine infectious anemia virus resists the antiretroviral activity of equine APOBEC3 proteins through a packaging-independent mechanism
The artiodactyl APOBEC3 innate immune repertoire shows evidence for a multi-functional domain organization that existed in the ancestor of placental mammals
Genetic editing of HBV DNA by monodomain human APOBEC3 cytidine deaminases and the recombinant nature of APOBEC3G
Structure-function analyses point to a polynucleotide-accommodating groove essential for APOBEC3A restriction activities
Somatic hypermutation of human mitochondrial and nuclear DNA by APOBEC3 cytidine deaminases, a pathway for DNA catabolism
Genetic editing of herpes simplex virus 1 and Epstein-Barr herpesvirus genomes by human APOBEC3 cytidine deaminases in culture and in vivo
An ancient history of gene duplications, fusions and losses in the evolution of APOBEC3 mutators in mammals
Cervical cancers require the continuous expression of the human papillomavirus type 16 E7 oncoprotein even in the presence of the viral E6 oncoprotein
Subcellular localization of the APOBEC3 proteins during mitosis and implications for genomic DNA deamination
IFN-α induces APOBEC3G, F, and A in immature dendritic cells and limits HIV-1 spread to CD4+ T cells
Depletion of HPV16 early genes induces autophagy and senescence in a cervical carcinogenesis model, regardless of viral physical state
Human APOBEC3A isoforms translocate to the nucleus and induce DNA double strand breaks leading to cell stress and death
CpG dinucleotide frequencies reveal the role of host methylation capabilities in parvovirus evolution
APOBEC3 deaminases induce hypermutation in human papillomavirus 16 DNA upon beta interferon stimulation
Full genome ultra-deep pyrosequencing associates G-to-A hypermutation of the hepatitis B virus genome with the natural progression of hepatitis B
Host restriction of murine gammaherpesvirus 68 replication by human APOBEC3 cytidine deaminases but not murine APOBEC3
Association of a germline copy number polymorphism of APOBEC3A and APOBEC3B with burden of putative APOBEC-dependent mutations in breast cancer
The antiviral restriction factors IFITM1, 2 and 3 do not inhibit infection of human papillomavirus, cytomegalovirus and adenovirus
APOBEC-mediated cytosine deamination links PIK3CA helical domain mutations to human papillomavirus-driven tumor development
Inactivation of the human papillomavirus E6 or E7 gene in cervical carcinoma cells by using a bacterial CRISPR/Cas RNA-guided endonuclease
A prevalent cancer susceptibility APOBEC3A hybrid allele bearing APOBEC3B 3'UTR enhances chromosomal DNA damage
Interferon treatment of human keratinocytes harboring extrachromosomal, persistent HPV-16 plasmid genomes induces de novo viral integration
Human papillomavirus E6 triggers upregulation of the antiviral and cancer genomic DNA deaminase APOBEC3B.
APOBEC3B expression in breast cancer reflects cellular proliferation, while a deletion polymorphism is associated with immune activation
Identification of APOBEC3B promoter elements responsible for activation by human papillomavirus type 16 E6
An APOBEC3A hypermutation signature is distinguishable from the signature of background mutagenesis by APOBEC3B in human cancers
Depletion of CpG Dinucleotides in Papillomaviruses and Polyomaviruses: A Role for Divergent Evolutionary Pressures
APOBEC-induced mutations in human cancers are strongly enriched on the lagging DNA strand during replication
Analysis of functional germline variants in APOBEC3 and driver genes on breast cancer risk in Moroccan study population
Subtypes of HPV-Positive Head and Neck Cancers Are Associated with HPV Characteristics, Copy Number Alterations, PIK3CA Mutation, and Pathway Signatures
Analysis of APOBEC3A/3B germline deletion polymorphism in breast, cervical and oral cancers from South India and its impact on miRNA regulation
In Vivo Examination of Mouse APOBEC3- and Human APOBEC3A- and APOBEC3G-Mediated Restriction of Parvovirus and Herpesvirus Infection in Mouse Models
Association of germline variants in the APOBEC3 region with cancer risk and enrichment with APOBEC-signature mutations in tumors
Landscape of immunogenic tumor antigens in successful immunotherapy of virally induced epithelial cancer
Crystal structure of APOBEC3A bound to single-stranded DNA reveals structural basis for cytidine deamination and specificity
Human Papillomaviruses Preferentially Recruit DNA Repair Factors to Viral Genomes for Rapid Repair and Amplification
The DNA deaminase APOBEC3B interacts with the cell-cycle protein CDK4 and disrupts CDK4-mediated nuclear import of Cyclin D1.
Distribution and difference of APOBEC-induced mutations in the TpCpW context of HBV DNA between HCC and non-HCC.
Association of HPV35 with cervical carcinogenesis among women of African ancestry: Evidence of viral-host interaction with implications for disease intervention.
Endogenous APOBEC3B overexpression characterizes HPV-positive and HPV-negative oral epithelial dysplasias and head and neck cancers.
Expression of estrogen receptor alpha is associated with pathogenesis and prognosis of human papillomavirus-positive oropharyngeal cancer
Expansions, diversification, and interindividual copy number variations of AID/APOBEC family cytidine deaminase genes in lampreys
High-Risk Human Papillomaviral Oncogenes E6 and E7 Target Key Cellular Pathways to Achieve Oncogenesis
Identification of human papillomavirus type 16 variants circulating in the Calabria region by sequencing and phylogenetic analysis of HPV16 from cervical smears
HPV-16/18 E6-induced APOBEC3B expression associates with proliferation of cervical cancer cells and hypomethylation of Cyclin D1.
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