scholarly journals HPV Meets APOBEC: New Players in Head and Neck Cancer

2021 ◽  
Vol 22 (3) ◽  
pp. 1402
Author(s):  
Giuseppe Riva ◽  
Camilla Albano ◽  
Francesca Gugliesi ◽  
Selina Pasquero ◽  
Sergio Fernando Castillo Pacheco ◽  
...  

Besides smoking and alcohol, human papillomavirus (HPV) is a factor promoting head and neck squamous cell carcinoma (HNSCC). In some human tumors, including HNSCC, a number of mutations are caused by aberrantly activated DNA-modifying enzymes, such as the apolipoprotein B mRNA editing enzyme catalytic polypeptide-like (APOBEC) family of cytidine deaminases. As the enzymatic activity of APOBEC proteins contributes to the innate immune response to viruses, including HPV, the role of APOBEC proteins in HPV-driven head and neck carcinogenesis has recently gained increasing attention. Ongoing research efforts take the cue from two key observations: (1) APOBEC expression depends on HPV infection status in HNSCC; and (2) APOBEC activity plays a major role in HPV-positive HNSCC mutagenesis. This review focuses on recent advances on the role of APOBEC proteins in HPV-positive vs. HPV-negative HNSCC.

2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Valdimara C. Vieira ◽  
Marcelo A. Soares

The APOBEC family of proteins comprises deaminase enzymes that edit DNA and/or RNA sequences. The APOBEC3 subgroup plays an important role on the innate immune system, acting on host defense against exogenous viruses and endogenous retroelements. The role of APOBEC3 proteins in the inhibition of viral infection was firstly described for HIV-1. However, in the past few years many studies have also shown evidence of APOBEC3 action on other viruses associated with human diseases, including HTLV, HCV, HBV, HPV, HSV-1, and EBV. APOBEC3 inhibits these viruses through a series of editing-dependent and independent mechanisms. Many viruses have evolved mechanisms to counteract APOBEC effects, and strategies that enhance APOBEC3 activity constitute a new approach for antiviral drug development. On the other hand, novel evidence that editing by APOBEC3 constitutes a source for viral genetic diversification and evolution has emerged. Furthermore, a possible role in cancer development has been shown for these host enzymes. Therefore, understanding the role of deaminases on the immune response against infectious agents, as well as their role in human disease, has become pivotal. This review summarizes the state-of-the-art knowledge of the impact of APOBEC enzymes on human viruses of distinct families and harboring disparate replication strategies.


Author(s):  
S. GEJALAKSHMI ◽  
N. HARIKRISHNAN ◽  
S. KOMAL

Apobec is an apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like" is a family of deaminases. It has two types of APOBEC enzymes n-terminal of apobec enzyme and C-terminal of APOBEC enzyme. N-terminal domain is catalytic domain and C-terminal domain is a pseudo catalytic domain. Pathogen and cellular genome undergo mutation by human DNA cytosine to uracil deaminases. Three subtypes of APOBEC3D. APOBEC3F, APOBEC3G and APOBEC3H restrict human deficiency virus-1. Two APOBEC enzymes are the sources of somatic mutagenesis in cancer cells that drive tumor evolution and manifest clinically as theraphy resistance. This review of the APOBEC family will focus on an open question in regulation, namely what role the interactions of these proteins with RNA have in editing substrate recognition or allosteric regulation of DNA mutagenic and host-defense activities.


1999 ◽  
Vol 40 (4) ◽  
pp. 623-635 ◽  
Author(s):  
Ba-Bie Teng ◽  
Scott Ochsner ◽  
Qian Zhang ◽  
Kizhake V. Soman ◽  
Paul P. Lau ◽  
...  

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Maria Pujantell ◽  
Roger Badia ◽  
Iván Galván-Femenía ◽  
Edurne Garcia-Vidal ◽  
Rafael de Cid ◽  
...  

AbstractInfection by human papillomavirus (HPV) alters the microenvironment of keratinocytes as a mechanism to evade the immune system. A-to-I editing by ADAR1 has been reported to regulate innate immunity in response to viral infections. Here, we evaluated the role of ADAR1 in HPV infection in vitro and in vivo. Innate immune activation was characterized in human keratinocyte cell lines constitutively infected or not with HPV. ADAR1 knockdown induced an innate immune response through enhanced expression of RIG-I-like receptors (RLR) signaling cascade, over-production of type-I IFNs and pro-inflammatory cytokines. ADAR1 knockdown enhanced expression of HPV proteins, a process dependent on innate immune function as no A-to-I editing could be identified in HPV transcripts. A genetic association study was performed in a cohort of HPV/HIV infected individuals followed for a median of 6 years (range 0.1–24). We identified the low frequency haplotype AACCAT significantly associated with recurrent HPV dysplasia, suggesting a role of ADAR1 in the outcome of HPV infection in HIV+ individuals. In summary, our results suggest that ADAR1-mediated innate immune activation may influence HPV disease outcome, therefore indicating that modification of innate immune effectors regulated by ADAR1 could be a therapeutic strategy against HPV infection.


2020 ◽  
Vol 29 (2) ◽  
pp. 120-8
Author(s):  
Rizkyana Avissa ◽  
Silvia Tri Widyaningtyas ◽  
Budiman Bela

BACKGROUND Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like-3G (APOBEC3G) can abolish HIV infection by inducing lethal mutations in the HIV genome. The HIV protein virion infectivity factor (Vif) can interact with APOBEC3G protein and cause its degradation. Development of a method that can screen substances inhibiting the APOBEC3G-Vif interaction is necessary for identification of substances that potentially used in anti-HIV drug development. In order to increase expression of recombinant APOBEC3G protein that will be used in APOBEC3G-Vif interaction assay, we developed an optimized APOBEC3G gene for expression in Escherichia coli.  METHODS The gene coding APOBEC3G was codon-optimized in accordance with prokaryotic codon using DNA 2.0 software to avoid bias codons that could inhibit its expression. The APOBEC3G gene was synthesized and sub-cloned into pQE80L plasmid vector. pQE80L containing APOBEC3G was screened by polymerase chain reaction, enzyme restriction, and sequencing to verify its DNA sequence. The recombinant APOBEC3G was expressed in E. coli under isopropyl-β-D-thiogalactoside (IPTG) induction and purified by using nickel-nitrilotriacetic acid (Ni-NTA) resin.  RESULTS The synthetic gene coding APOBEC3G was successfully cloned into the pQE80L vector and could be expressed abundantly in E. coli BL21 in the presence of IPTG.  CONCLUSIONS Recombinant APOBEC3G is robustly expressed in E. coli BL21, and the APOBEC3G protein could be purified by using Ni-NTA. The molecular weight of the recombinant APOBEC3G produced is smaller than the expected value. However, the protein is predicted to be able to interact with Vif because this interaction is determined by a specific domain located on the N-terminal of APOBEC3G. 


2000 ◽  
Vol 275 (26) ◽  
pp. 19848-19856 ◽  
Author(s):  
Heinrich Lellek ◽  
Romy Kirsten ◽  
Ines Diehl ◽  
Frank Apostel ◽  
Friedrich Buck ◽  
...  

2007 ◽  
Vol 195 (7) ◽  
pp. 960-964 ◽  
Author(s):  
Mara Biasin ◽  
Luca Piacentini ◽  
Sergio Lo Caputo ◽  
Yasuyoshi Kanari ◽  
Giuliana Magri ◽  
...  

Genomics ◽  
1994 ◽  
Vol 24 (2) ◽  
pp. 414-415 ◽  
Author(s):  
Rafael Espinosa ◽  
Toru Funahashi ◽  
Christos Hadjiagapiou ◽  
Michelle M. Le Beau ◽  
Nicholas O. Davidson

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