Article
Biochemistry & Molecular Biology
Kailash Chand, Muneesh Kumar Barman, Payel Ghosh, Debashis Mitra
Summary: The HSP40/DNAJ family of proteins is highly diverse and contains around 49 isoforms in humans. Some of these isoforms have been shown to play functional roles in the pathogenesis of viruses, including HIV-1. Our study found that several isoforms of HSP40 were significantly modulated during HIV-1 infection in T cells at the mRNA level. We investigated the biological role of these modulated isoforms and found that certain isoforms positively regulate virus replication, while others negatively regulate it. Additionally, we discovered that one isoform, DNAJB8, specifically regulates the infectivity of progeny virions by downregulating the Vif protein.
Article
Multidisciplinary Sciences
Fumiaki Ito, Ana L. Alvarez-Cabrera, Shiheng Liu, Hanjing Yang, Anna Shiriaeva, Z. Hong Zhou, Xiaojiang S. Chen
Summary: Human APOBEC3G (A3G) is a virus restriction factor that inhibits HIV-1 replication and triggers lethal hypermutation. HIV-1 viral infectivity factor (Vif) hijacks a cellular E3 ubiquitin ligase complex to target A3G and evade immune response. Understanding the molecular mechanism of this interaction is crucial for developing antiretroviral therapeutics.
Review
Microbiology
Daniel J. Salamango, Reuben S. Harris
Summary: Accessory proteins like Vif play a crucial role in distinguishing primate immunodeficiency viruses such as HIV-1, by not only antagonizing APOBEC3 enzymes but also triggering cell cycle arrest through the degradation of PPP2R5 proteins. These functions of Vif have opened up new avenues for accessory protein research and potential opportunities for drug development.
FRONTIERS IN MICROBIOLOGY
(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
Biochemistry & Molecular Biology
Camille Libre, Tanja Seissler, Santiago Guerrero, Julien Batisse, Cedric Verriez, Benjamin Stupfler, Orian Gilmer, Romina Cabrera-Rodriguez, Melanie M. Weber, Agustin Valenzuela-Fernandez, Andrea Cimarelli, Lucie Etienne, Roland Marquet, Jean-Christophe Paillart
Summary: The HIV-1 Vif protein decreases the expression of cellular restriction factors APOBEC3G, A3F, A3D, and A3H, which inhibit viral replication. The translation of A3G is regulated by a conserved uORF in the 5' untranslated region of its mRNA. This uORF is also important for Vif-mediated translation inhibition and redirection of A3G mRNA into stress granules.
Review
Virology
Benjamin Stupfler, Cedric Verriez, Sarah Gallois-Montbrun, Roland Marquet, Jean-Christophe Paillart
Summary: The ubiquitin-proteasome system plays a crucial role in normal cell physiology and during viral infections. HIV-1 viral infectivity factor (Vif) has been shown to counteract cellular deaminases by recruiting E3-ubiquitin ligase complex, leading to their polyubiquitination and degradation. Research on the degradation-independent inhibition of A3s by Vif remains limited, but it has been shown to impede A3s through other processes.
Article
Biochemical Research Methods
Robyn M. Kaake, Ignacia Echeverria, Seung Joong Kim, John Von Dollen, Nicholas M. Chesarino, Yuqing Feng, Clinton Yu, Hai Ta, Linda Chelico, Lan Huang, John Gross, Andrej Sali, Nevan J. Krogan
Summary: The study introduced a pipeline for structural characterization of host-pathogen protein complexes using integrative structure modeling based on chemical cross-links and residue-protein contacts inferred from mutagenesis studies. The approach was applied to determine the structure of the (A3G-Vif-CRL5-CBF beta) complex, revealing insights into the interactions within the complex. The model created using this approach was validated and used to rationalize previous structural, mutagenesis, and functional data related to the A3G-Vif interface.
MOLECULAR & CELLULAR PROTEOMICS
(2021)
Article
Multidisciplinary Sciences
Yen-Li Li, Caroline A. Langley, Caleigh M. Azumaya, Ignacia Echeverria, Nicholas M. Chesarino, Michael Emerman, Yifan Cheng, John D. Gross
Summary: The APOBEC3 (A3) proteins are host antiviral cellular proteins that hypermutate the viral genome of diverse viral families. A3G protein of humans binds to HIV-1 Vif and inhibits its function by RNA-mediated mechanisms. This discovery sheds light on the molecular arms race between viruses and hosts.
Article
Infectious Diseases
Basma Abdi, Sidonie Lambert-Niclot, Marc Wirden, Aude Jary, Elisa Teyssou, Sophie Sayon, Romain Palich, Roland Tubiana, Anne Simon, Marc-Antoine Valantin, Christine Katlama, Laurence Morand-Joubert, Vincent Calvez, Anne-Genevieve Marcelin, Cathia Soulie
Summary: The study reveals an association between virological and clinical factors and APOBEC3 editing activity, with G-to-A mutations and stop codons in the reverse transcriptase gene as markers of HIV-1 diversity among virologically suppressed patients. A higher prevalence of hypermutated sequences was found in the APOBEC+ group, while the total cell-associated HIV-1 DNA level was lower in this group compared to the APOBEC- group.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Virology
Nicholas M. Chesarino, Michael Emerman
Summary: APOBEC3G (A3G) is an antiviral protein that restricts retroviruses like HIV. HIV-1 Vif has evolved to antagonize A3G. Two rapidly evolving sites in A3G act as a barrier to cross-species transmission of retroviruses. This study explores the evolutionary space of A3G at these sites to understand the advantage gained by HIV-1 Vif in its arms race with A3G.
JOURNAL OF VIROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Xiaoxuan Yan, Chao Chen, Chunxi Wang, Wenxian Lan, Jianguo Wang, Chunyang Cao
Summary: APOBEC3G is a member of the cytosine deaminase family with innate immune functions. This research screened and identified five asymmetrical disulfides that inhibit the interaction between A3G and Vif, restoring A3G expression and opening up possibilities for the discovery of new anti-HIV drugs.
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
(2022)
Article
Biochemistry & Molecular Biology
Amjad Ali, Vivek Kumar, Akhil C. Banerjea
Summary: HIV-1 accessory protein Vif neutralizes the cellular restriction factor APOBEC3G through ubiquitination and degradation, which is regulated by the E3 ubiquitin ligase CHIP. Increased CHIP expression leads to reduced Vif levels and destabilization of APOBEC3G, confirming CHIP's role as a negative regulator of Vif.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
A. S. Tikhonov, R. R. Mintaev, D. V. Glazkova, E. V. Bogoslovskaya, G. A. Shipulin
Summary: The mechanisms for protecting the human body from viral or bacterial agents are diverse. APOBEC3 family proteins, including APOBEC3G, play an important role in congenital immunity and can protect against HIV. However, viral protein Vif counteracts the action of APOBEC3G by promoting its degradation. This review discusses potential strategies to enhance the anti-HIV activity of APOBEC3G and utilize modified APOBEC3G in HIV gene therapy.
Article
Multidisciplinary Sciences
Takahide Kouno, Satoshi Shibata, Megumi Shigematsu, Jaekyung Hyun, Tae Gyun Kim, Hiroshi Matsuo, Matthias Wolf
Summary: HIV-1 utilizes Vif to degrade A3G, an antiviral factor, by hijacking a host ubiquitin ligase complex. The cryoEM structure of the A3G-Vif complex and A3G ubiquitination in vitro using solubility-enhanced variants were reported. The study reveals the atomic model of the A3G-Vif interface, which involves both protein-protein interaction and RNA. The findings suggest potential pharmacophores for inhibiting the A3G-Vif interaction.
NATURE COMMUNICATIONS
(2023)
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
Biochemistry & Molecular Biology
Orian Gilmer, Elodie Mailler, Jean-Christophe Paillart, Assia Mouhand, Carine Tisne, Johnson Mak, Redmond P. Smyth, Roland Marquet, Valerie Vivet-Boudou
Summary: Maturation of HIV-1 viral particles is essential for infectivity. While the structural rearrangements of viral proteins during maturation are well-known, the maturation of genomic RNA (gRNA) structure is less explored. This study investigates the interactions between Pr55(Gag) or its maturation products and the gRNA region, revealing their distinct contributions to gRNA structural maturation.
Article
Biochemistry & Molecular Biology
Camille Libre, Tanja Seissler, Santiago Guerrero, Julien Batisse, Cedric Verriez, Benjamin Stupfler, Orian Gilmer, Romina Cabrera-Rodriguez, Melanie M. Weber, Agustin Valenzuela-Fernandez, Andrea Cimarelli, Lucie Etienne, Roland Marquet, Jean-Christophe Paillart
Summary: The HIV-1 Vif protein decreases the expression of cellular restriction factors APOBEC3G, A3F, A3D, and A3H, which inhibit viral replication. The translation of A3G is regulated by a conserved uORF in the 5' untranslated region of its mRNA. This uORF is also important for Vif-mediated translation inhibition and redirection of A3G mRNA into stress granules.
Article
Biochemistry & Molecular Biology
Romina Cabrera-Rodriguez, Silvia Perez-Yanes, Rafaela Montelongo, Jose M. Lorenzo-Salazar, Judith Estevez-Herrera, Jonay Garcia-Luis, Antonio Inigo-Campos, Luis A. Rubio-Rodriguez, Adrian Munoz-Barrera, Rodrigo Trujillo-Gonzalez, Roberto Dorta-Guerra, Concha Casado, Maria Pernas, Julia Blanco, Carlos Flores, Agustin Valenzuela-Fernandez
Summary: TDP-43 plays a significant role in regulating cell permissivity to HIV-1 infection, affecting viral fusion and infection capacities by altering HDAC6 levels and associated tubulin-deacetylase anti-HIV-1 activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Letter
Infectious Diseases
Laura Ciuffreda, Julia Alcoba-Florez, Jose M. Lorenzo-Salazar, Helena Gil-Campesino, Diego Garcia-Martinez de Artola, Oscar Diez-Gil, Hector Rodriguez-Perez, Antonio Inigo-Campos, Agustin Valenzuela-Fernandez, Rafaela Gonzalez-Montelongo, Carlos Flores
JOURNAL OF INFECTION
(2022)
Article
Biochemistry & Molecular Biology
Nicole Kaminski, Anne R. Wondisford, Youngho Kwon, Michelle Lee Lynskey, Ragini Bhargava, Jonathan Barroso-Gonzalez, Laura Garcia-Exposito, Boxue He, Meng Xu, Dattatreya Mellacheruvu, Simon C. Watkins, Mauro Modesti, Kyle M. Miller, Alexey Nesvizhskii, Huaiying Zhang, Patrick Sung, Roderick J. O'Sullivan
Summary: In this study, the researchers found that RAD51AP1 interacts with TERRA and utilizes it to generate D and R-loop HR intermediates. RAD51AP1 binds to and stabilizes TERRA-containing R-loops, playing a role in the suppression of TERRA and prevention of TRCs during ALT-HDR. These findings provide insights into the important role of RAD51AP1 in the ALT mechanism and regulation of TERRA.
Article
Multidisciplinary Sciences
Robert Drillien, Karine Pradeau-Aubreton, Julien Batisse, Joelle Mezher, Emma Schenckbecher, Justine Marguin, Eric Ennifar, Marc Ruff
Summary: This study reports further improvements in the production of full length, biologically active proteins in mammalian cells using Modified vaccinia virus Ankara encoding the bacteriophage T7 RNA polymerase (MVA-T7). The methods developed in this study allow for easier and faster recombinant virus isolation, scale-up of protein production, and simultaneous synthesis of multiple polypeptides belonging to a protein complex using a single virus vector.
Review
Biotechnology & Applied Microbiology
Agustin Valenzuela-Fernandez, Romina Cabrera-Rodriguez, Laura Ciuffreda, Silvia Perez-Yanes, Judith Estevez-Herrera, Rafaela Gonzalez-Montelongo, Julia Alcoba-Florez, Rodrigo Trujillo-Gonzalez, Diego Garcia-Martinez de Artola, Helena Gil-Campesino, Oscar Diez-Gil, Jose M. Lorenzo-Salazar, Carlos Flores, Jonay Garcia-Luis
Summary: The outbreak of the novel coronavirus has prompted the development of nanotechnological applications and nano-based materials for the prevention, diagnosis, and treatment of COVID-19. These advancements have enabled rapid and accurate surveillance and diagnosis of SARS-CoV-2 infection, as well as monitoring of virus mutations and disease severity, aiding in decision-making by authorities and public health services.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Microbiology
Damien Bonnard, Erwann Le Rouzic, Matthew R. Singer, Zhe Yu, Frederic Le Strat, Claire Batisse, Julien Batisse, Celine Amadori, Sophie Chasset, Valerie E. Pye, Stephane Emiliani, Benoit Ledoussal, Marc Ruff, Francois Moreau, Peter Cherepanov, Richard Benarous
Summary: HIV-1 integrase-LEDGF allosteric inhibitors (INLAIs) bind to the same site on viral protein as the host factor LEDGF/p75. These molecules promote hyper-multimerization of HIV-1 integrase, disrupting viral particle maturation. A new series of INLAIs based on a benzene scaffold exhibit potent antiviral activity. They inhibit the late stages of HIV-1 replication and remain active against drug-resistant variants.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Review
Biochemistry & Molecular Biology
Romina Cabrera-Rodriguez, Silvia Perez-Yanes, Iria Lorenzo-Sanchez, Rodrigo Trujillo-Gonzalez, Judith Estevez-Herrera, Jonay Garcia-Luis, Agustin Valenzuela-Fernandez
Summary: HIV-1 uses various strategies to overcome the cytoskeletal barrier, allowing it to enter and infect cells and then spread infection. It modifies the cytoskeletal organization and dynamics by acting on adaptors and molecular motors, and regulates cytoskeleton dynamics to ensure viral expression and assembly.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
E. Mauro, D. Lapaillerie, C. Tumiotto, C. Charlier, F. Martins, S. F. Sousa, M. Metifiot, P. Weigel, K. Yamatsugu, M. Kanai, H. Munier-Lehmann, C. Richetta, M. Maisch, J. Dutrieux, J. Batisse, M. Ruff, O. Delelis, P. Lesbats, V. Parissi
Summary: Researchers used AlphaLISA technology to monitor the interaction between retroviral intasomes and nucleosomes, and identified drugs that disrupt or prevent their association, inhibiting HIV-1 integration.
Article
Cell Biology
Jose Rivera Alvarez, Laure Asselin, Peggy Tilly, Roxane Benoit, Claire Batisse, Ludovic Richert, Julien Batisse, Bastien Morlet, Florian Levet, Noemie Schwaller, Yves Mely, Marc Ruff, Anne-Cecile Reymann, Juliette D. Godin
Summary: Completion of neuronal migration is crucial for brain development. Kif21b, a plus-end-directed kinesin motor protein, has been found to play a physiological role in the radial migration of projection neurons in the developing cortex. It regulates the locomotion of newborn neurons guided by radial glia independently of microtubules, and directly binds and regulates the actin cytoskeleton during migration. The Kif21b-mediated regulation of actin cytoskeleton dynamics influences branching and nucleokinesis during neuronal locomotion.
Article
Biochemistry & Molecular Biology
Cecilia Rocchi, Camille Louvat, Adriana Erica Miele, Julien Batisse, Christophe Guillon, Lionel Ballut, Daniela Lener, Matteo Negroni, Marc Ruff, Patrice Gouet, Francesca Fiorini
Summary: Recent evidence suggests that HIV-1 Integrase (IN) plays a critical role in the morphogenesis of the viral particle and the stability of viral genomic RNA (gRNA) in host cells. The C-terminal tail of IN interacts with the apical structure of TAR RNA, modifying its structure and facilitating the binding of HIV transcriptional trans-activator Tat to TAR. This process eventually displaces IN from TAR. These findings provide insights into the mechanism of IN in the early stages of proviral transcription and could contribute to the development of anti-HIV-1 therapeutics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)