Review
Biochemistry & Molecular Biology
Atanu Maiti, Shurong Hou, Celia A. Schiffer, Hiroshi Matsuo
Summary: APOBEC3 enzymes play a crucial role in regulating antiviral response in HIV, but may also contribute to diversity in cancer. Recent studies have revealed the diversity of epitopes involved in APOBEC3 binding to nucleic acids, highlighting the importance of the interplay between these interactions in uncovering how APOBEC3s recognize and process their substrates.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Fumiaki Ito, Ana L. Alvarez-Cabrera, Kyumin Kim, Z. Hong Zhou, Xiaojiang S. Chen
Summary: The study reveals the mechanism by which HIV-1 virus evades the antiviral response of human APOBEC3 (A3) cytidine deaminases. The cryo-EM structures of the viral infectivity factor (Vif) in complex with A3H, CBF-ss, and components of CUL5 ubiquitin ligase shed light on the interplay between HIV and humans.
NATURE COMMUNICATIONS
(2023)
Article
Biochemical Research Methods
Zi-Rui Huang, Xiang-Rong Chen, Dan-Feng Liu, You-Zhi Cui, Bing-Zhi Li, Ying-Jin Yuan
Summary: Random mutations in the genome can enhance diversity and drive the evolution of organisms. Efficient mutagenesis techniques can greatly accelerate the evolutionary process. In this study, a targeted mutagenesis system called MutaT7(trans) was developed to significantly increase mutation rate and generate mutations across all four nucleotides in yeast.
BIOTECHNOLOGY JOURNAL
(2023)
Article
Virology
Jeremy Ratcliff, Peter Simmonds
Summary: After spillover, viruses need to adapt to new antiviral responses in their new hosts. In mammals, cellular defenses include viral nucleic acid editing pathways mediated by ADAR and APOBECs. APOBEC3 paralogs have influenced the evolution of HIV and show evidence of mutagenic impact on monkeypox virus and SARS-CoV-2. ADAR-1 induces A-I substitutions in RNA, but its role in virus adaptation and epigenetic modifications like methylation is still unclear. Nucleic acid editing restricts viral evolution and may limit viral-host range.
CURRENT OPINION IN VIROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yelena Britan-Rosich, Jing Ma, Eran Kotler, Faizan Hassan, Alexander Botvinnik, Yoav Smith, Ofra Moshel, Abed Nasereddin, Gunjan Sharma, Eli Pikarsky, Susan Ross, Moshe Kotler
Summary: APOBEC3G (A3G) promotes repair of DNA double-strand breaks (DSBs) and facilitates error-free rejoining, in addition to its role in immunity. Inhibiting A3G may improve the efficacy of genotoxic therapies, while enhancing A3G activity may reduce acute radiation syndrome.
Article
Medicine, General & Internal
Simin Zhao, Baisong Zheng, Liuli Wang, Wenzhe Cui, Chunlai Jiang, Zhuo Li, Wenying Gao, Wenyan Zhang
Summary: This study reveals that ubiquitin-specific protease 3 (USP3) inhibits HIV-1 replication by stabilizing antiviral factor A3G and increasing its mRNA level. Furthermore, the expression of USP3 is positively correlated with A3G expression and CD4(+) T-cell counts.
CHINESE MEDICAL JOURNAL
(2022)
Article
Virology
Madushi Wanaguru, Kate N. Bishop
Summary: The p12 protein of MLV and the p6 protein of HIV-1 are both supplementary Gag cleavage products that carry proline-rich motifs facilitating virus budding. While p12 is essential for early viral replication events, the role of Vpr and mature p6 in early replication remains unclear. Mutagenesis studies suggest that p6 is not crucial for early viral replication, with most mature p6 and recruited Vpr being rapidly lost upon target cell entry.
JOURNAL OF VIROLOGY
(2021)
Article
Virology
Ananda Ayyappan Jaguva Vasudevan, Kannan Balakrishnan, Andre Franken, Aikaterini Krikoni, Dieter Haeussinger, Tom Luedde, Carsten Muenk
Summary: The study demonstrated that the A3A protein has antiviral activity against certain viruses, including Moloney-MLV and related strains. The glycosylated Gag of MLV can affect the encapsidation and activity of A3A, potentially leading to A3A-induced mutations in gene therapy applications.
Review
Chemistry, Medicinal
Qiqi Bao, Jinming Zhou
Summary: The host restriction factor APOBEC3G (A3G) restricts Vif-deficient HIV-1 replication by causing mutations during viral DNA synthesis. HIV-1 expresses Vif protein to counteract A3G by degrading it. The self-association of Vif with A3G proteins, chaperones, and factors of the ubiquitination machinery is a potential target for novel anti-HIV drugs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Plant Sciences
Yingying Yang, Bastian Oldenkott, Shyam Ramanathan, Elena Lesch, Mizuki Takenaka, Mareike Schallenberg-Ruedinger, Volker Knoop
Summary: Protein factors for specific RNA editing events in plant mitochondria and chloroplasts have unique RNA-binding PPRs and DYW domains. The function of E1 and E2 motifs in these factors is unclear. In this study, the tolerance of PPR56 and PPR65 for creating chimeras by replacing their C-terminal protein regions was investigated. Results showed that heterologous DYW domains can restrict or widen the spectrum of off-targets in the bacterial transcriptome for PPR56, possibly due to their preference for the immediate sequence of the editing site and long-range impact on upstream PPRs' nucleotide selectivity.
Article
Biochemistry & Molecular Biology
Sajjad Ahmad, Yasir Waheed, Saba Ismail, Saadia Bhatti, Sumra Wajid Abbasi, Khalid Muhammad
Summary: This study aimed to predict phytochemicals with high binding affinity to SARS-CoV-2 helicase, as a potential therapeutic strategy against COVID-19.
Article
Virology
Cody J. Warren, Mario L. Santiago, Dohun Pyeon
Summary: This review focuses on the role of APOBEC3 proteins in HPV infection and HPV-driven oncogenesis. Elevated APOBEC3 expression and activity have been found to be significant contributors to somatic mutagenesis in HPV-positive tumors.
ANNUAL REVIEW OF VIROLOGY
(2022)
Article
Multidisciplinary Sciences
Rosana S. Molina, Gordon Rix, Amanuella A. Mengiste, Beatriz Alvarez, Daeje Seo, Haiqi Chen, Juan E. Hurtado, Qiong Zhang, Jorge Donato Garcia-Garcia, Zachary J. Heins, Patrick J. Almhjell, Frances H. Arnold, Ahmad S. Khalil, Andrew D. Hanson, John E. Dueber, David Schaffer, Fei Chen, Seokhee Kim, Luis Angel Fernandez, Matthew D. Shoulders, Chang C. Liu
Summary: By achieving rapid cycles of mutation, amplification, and selection fully inside living cells, genetic systems have advanced the scale, depth, and overall power of directed evolution, accessing important new areas of protein evolution and engineering.
NATURE REVIEWS METHODS PRIMERS
(2022)
Article
Oncology
Anni I. Soikkeli, Minna K. Kylaniemi, Harri Sihto, Jukka Alinikula
Summary: This study explored the contribution of activation-induced cytidine deaminase (AID)/APOBEC family cytidine deaminases to Merkel cell polyomavirus (MCPyV) induced Merkel cell carcinoma (MCC). The study found cytosine-targeting mutations in the MCPyV LT region of MCCs, and observed a strong APOBEC3 mutation signature in MCC sequences.
CANCER RESEARCH COMMUNICATIONS
(2022)