Article
Pharmacology & Pharmacy
Taizhen Liang, Ziyao Wu, Yibin Li, Chao Li, Kangni Zhao, Xinman Qiao, Heng Duan, Xuanxuan Zhang, Shuwen Liu, Baomin Xi, Lin Li
Summary: The persistence of HIV-1 latent reservoir presents a major challenge in finding a cure for HIV-1. Existing latency-reversing agents (LRAs) have not proven to be effective and safe in reactivating HIV-1 latency. In this study, a new small molecule compound called Q205 was developed and shown to effectively reactivate latent HIV-1 without inducing potentially damaging cytokines.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Kyle D. Pedro, Luis M. Agosto, Jared A. Sewell, Kimberly A. Eberenz, Xianbao He, Juan I. Fuxman Bass, Andrew J. Henderson
Summary: Through a high-throughput screen, researchers identified 42 human transcription factors and 85 protein-DNA interactions related to HIV-1 and HIV-2, shedding light on their roles in HIV replication, transcription, and latency. Experimental results confirmed that transcription factors like KLF2, KLF3, and PLAGL1 have different regulatory effects on the transcription of HIV-1 and HIV-2.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Haruki Kitamura, Sayaka Sukegawa, Kouki Matsuda, Kousuke Tanimoto, Takuya Kobayakawa, Kazuho Takahashi, Hirokazu Tamamura, Kiyoto Tsuchiya, Hiroyuki Gatanaga, Kenji Maeda, Hiroaki Takeuchi
Summary: Combinational antiretroviral therapy (cART) successfully suppresses viral load but fails to eliminate HIV-1 reservoirs. "Shock and Kill" strategy using latently-reversing agents (LRAs) is being developed to reactivate latent HIV-1 and induce cell death. This study identified 4-phenylquinoline-8-amine (PQA) as a novel LRA candidate that effectively reactivated HIV-1 and induced cell death in latently-infected cells.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Joseph Hokello, Adhikarimayum Lakhikumar Sharma, Mudit Tyagi
Summary: This study reveals the roles of NF-kappa B, NFAT, and AP-1 transcription factors in the reactivation of latent HIV, and the competitive and synergistic relationships between them in regulating HIV transcription.
Article
Virology
Emily Cruz-Lorenzo, Nora-Guadalupe P. Ramirez, Jeon Lee, Sonali Pandhe, Lei Wang, Juan Hernandez-Doria, Adam M. Spivak, Vicente Planelles, Tianna Petersen, Mamta K. Jain, Elisabeth D. Martinez, Ivan D'Orso
Summary: This study discovered a small molecule activator that alters the state of CD4(+) T cells to promote transcription and reactivation of latent HIV-1 through a unique mechanism of action. The activator triggered oxidative stress and activated a redox-responsive program involving cell-signaling kinases and atypical transcription factors, resulting in changes in viral transcriptional rewiring.
Review
Virology
Ivan D'Orso, Christian V. Forst
Summary: This article reviews the use of viral dynamics models for studying HIV-1 latent infection. These models can explain the decline in viral load during antiretroviral therapy, the formation and clearance of latent reservoirs, the dynamics of viral blips, and more. Additionally, mathematical models can predict the efficacy of potential HIV-1 cure strategies and guide the design of new treatment trials.
Article
Virology
Awadh Alanazi, Andrey Ivanov, Namita Kumari, Xionghao Lin, Songping Wang, Dmytro Kovalskyy, Sergei Nekhai
Summary: This study identified a novel benzoxazole compound, T0516-4834, that disrupted Tat-TAR RNA interaction and inhibited Tat-induced transcription and HIV-1 infection, suggesting its potential as a new lead for anti-HIV-1 therapeutics.
Article
Microbiology
Melissa Stunnenberg, John L. van Hamme, Atze T. Das, Ben Berkhout, Teunis B. H. Geijtenbeek
Summary: The study reveals that mutations in the TAR hairpin structure and sequence of HIV-1 RNA genome can impact viral sensing, leading to increased antiviral immune responses. These findings highlight the robustness of HIV-1 RNA sensing mechanisms.
Article
Immunology
Alex Olson, Carolyn Coote, Jennifer E. Snyder-Cappione, Nina Lin, Manish Sagar
Summary: Individuals infected with HIV-1 experience increased inflammation with age, but this does not result in higher levels of HIV-1 transcription. While the older group showed higher inflammation levels, they also had higher levels of cell-associated RNA, with similar levels of intact proviruses compared to the younger group.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Review
Virology
Alexia Damour, Vera Slaninova, Ovidiu Radulescu, Edouard Bertrand, Eugenia Basyuk
Summary: This review summarizes the current advances in understanding the role of transcriptional stochasticity in HIV-1 latency. The stochastic switching of the viral promoter between ON and OFF states is the result of random binding dynamics of transcription factors and nucleosomes. Transcriptional bursts are controlled by core transcription factors, chromatin status, and RNA polymerase II pausing. Understanding this stochasticity will be crucial for developing effective therapeutic strategies.
Article
Virology
Shilpa Sonti, Adhikarimayum Lakhikumar Sharma, Mudit Tyagi
Summary: Understanding HIV latency in the Central Nervous System and HIV-1 associated neurological disorders is crucial for improving existing elimination strategies against the virus and developing potential therapeutic targets. Despite four decades of research, successful eradication of the virus post-infection remains a major challenge due to the persistence of the virus in anatomical reservoirs such as the CNS.
Article
Microbiology
Yue Zheng, Heidi L. Schubert, Parmit K. Singh, Laura J. Martins, Alan N. Engelman, Ivan D'Orso, Christopher P. Hill, Vicente Planelles
Summary: The study reveals a novel role of CPSF6 in HIV-1 transcription by regulating the stability of PP2A, which in turn affects the phosphorylation/dephosphorylation status of CDK9 and Pol II. This mechanism appears to be independent of CPSF6's known roles in cleavage and polyadenylation and integration of viral DNA.
Article
Multidisciplinary Sciences
Priya Sivaramakrishnan, Cameron Watkins, John Isaac Murray
Summary: Dynamic transcriptional changes are widespread in rapidly dividing developing embryos. The Caenorhabditis elegans embryo overcomes these constraints by producing high levels of transcription factor mRNAs. We estimated zygotic mRNA accumulation rates and identified core promoter elements associated with high transcription rates in the early C. elegans embryo.
Article
Multidisciplinary Sciences
Dajiang Li, Lilly M. Wong, Yuyang Tang, Brigitte Allard, Katherine S. James, George R. Thompson, Satya Dandekar, Edward P. Browne, Qingsheng Li, Jeremy M. Simon, Nancie M. Archin, David M. Margolis, Guochun Jiang
Summary: Activation of ISR/ATF4 signaling can reverse HIV latency and selectively eliminate HIV-positive CD4(+) T cells without affecting HIV-negative CD4(+) T cells.
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)
Article
Immunology
Jamaluddin Md Saha, Hongbing Liu, Pei-Wen Hu, Bryan C. Nikolai, Hulin Wu, Hongyu Miao, Andrew P. Rice
AIDS RESEARCH AND HUMAN RETROVIRUSES
(2018)
Article
Multidisciplinary Sciences
Archana Sehrawat, Lina Gao, Yuliang Wang, Armand Bankhead, Shannon K. McWeeney, Carly J. King, Jacob Schwartzman, Joshua Urrutia, William H. Bisson, Daniel J. Coleman, Sunil K. Joshi, Dae-Hwan Kim, David A. Sampson, Sheila Weinmann, Bhaskar V. S. Kallakury, Deborah L. Berry, Reina Haque, Stephen K. Van Den Eeden, Sunil Sharma, Jared Bearss, Tomasz M. Beer, George V. Thomas, Laura M. Heiser, Joshi J. Alumkal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2018)
Article
Oncology
Tamilla Nechiporuk, Stephen E. Kurtz, Olga Nikolova, Tingting Liu, Courtney L. Jones, Angelo D'Alessandro, Rachel Culp-Hill, Amanda d'Almeida, Sunil K. Joshi, Mara Rosenberg, Cristina E. Tognon, Alexey Danilov, Brian J. Druker, Bill H. Chang, Shannon K. McWeeney, Jeffrey W. Tyner
Article
Biology
Nathalie Javidi-Sharifi, Jacqueline Martinez, Isabel English, Sunil K. Joshi, Renata Scopim-Ribiero, David K. Edwards, Anupriya Agarwal, Claudia Lopez, Danielle Jorgens, Jeffrey W. Tyner, Brian J. Druker, Elie Traer
Article
Medicine, General & Internal
Emerson Y. Chen, Sunil K. Joshi, Audrey Tran, Vinay Prasad
JAMA INTERNAL MEDICINE
(2019)
Review
Oncology
Sunil K. Joshi, Monika A. Davare, Brian J. Druker, Cristina E. Tognon
Article
Virology
Sushama Telwatte, Sara Moron-Lopez, Dvir Aran, Peggy Kim, Christine Hsieh, Sunil Joshi, Mauricio Montano, Warner C. Greene, Atul J. Butte, Joseph K. Wong, Steven A. Yukl
Article
Hematology
Sunil K. Joshi, Kristin Qian, William H. Bisson, Kevin Watanabe-Smith, Ariane Huang, Daniel Bottomly, Elie Traer, Jeffrey W. Tyner, Shannon K. McWeeney, Monika A. Davare, Brian J. Druker, Cristina E. Tognon
Article
Oncology
Sunil K. Joshi, Jamie M. Keck, Christopher A. Eide, Daniel Bottomly, Elie Traer, Jeffrey W. Tyner, Shannon K. McWeeney, Cristina E. Tognon, Brian J. Druker
Letter
Hematology
Sunil K. Joshi, Setareh Sharzehi, Janet Pittsenbarger, Daniel Bottomly, Cristina E. Tognon, Shannon K. McWeeney, Brian J. Druker, Elie Traer
AMERICAN JOURNAL OF HEMATOLOGY
(2021)
Article
Oncology
Sunil K. Joshi, Tamilla Nechiporuk, Daniel Bottomly, Paul D. Piehowski, Julie A. Reisz, Janet Pittsenbarger, Andy Kaempf, Sara J. C. Gosline, Yi-Ting Wang, Joshua R. Hansen, Marina A. Gritsenko, Chelsea Hutchinson, Karl K. Weitz, Jamie Moon, Francesca Cendali, Thomas L. Fillmore, Chia-Feng Tsai, Athena A. Schepmoes, Tujin Shi, Osama A. Arshad, Jason E. McDermott, Ozgun Babur, Kevin Watanabe-Smith, Emek Demir, Angelo D'Alessandro, Tao Liu, Cristina E. Tognon, Jeffrey W. Tyner, Shannon K. McWeeney, Karin D. Rodland, Brian J. Druker, Elie Traer
Summary: The study reveals that the bone marrow microenvironment protects residual AML cells and AML cells develop resistance mechanisms over time. By integrating multiple methods, early resistant cells were found to undergo metabolic reprogramming and depend on AURKB, while late resistant cells are characterized by expansion of pre-existing NRAS mutant subclones and metabolic reprogramming.
Article
Oncology
Daniel Bottomly, Nicola Long, Anna Reister Schultz, Stephen E. Kurtz, Cristina E. Tognon, Kara Johnson, Melissa Abel, Anupriya Agarwal, Sammantha Avaylon, Erik Benton, Aurora Blucher, Uma Borate, Theodore P. Braun, Jordana Brown, Jade Bryant, Russell Burke, Amy Carlos, Bill H. Chang, Hyun Jun Cho, Stephen Christy, Cody Coblentz, Aaron M. Cohen, Amanda d'Almeida, Rachel Cook, Alexey Danilov, Kim-Hien T. Dao, Michie Degnin, James Dibb, Christopher A. Eide, Isabel English, Stuart Hagler, Heath Harrelson, Rachel Henson, Hibery Ho, Sunil K. Joshi, Brian Junio, Andy Kaempf, Yoko Kosaka, Ted Laderas, Matt Lawhead, Hyunjung Lee, Jessica T. Leonard, Chenwei Lin, Evan F. Lind, Selina Qiuying Liu, Pierrette Lo, Marc M. Loriaux, Samuel Luty, Julia E. Maxson, Tara Macey, Jacqueline Martinez, Jessica Minnier, Andrea Monteblanco, Motomi Mori, Quinlan Morrow, Dylan Nelson, Justin Ramsdill, Angela Rofelty, Alexandra Rogers, Kyle A. Romine, Peter Ryabinin, Jennifer N. Saultz, David A. Sampson, Samantha L. Savage, Robert Schuff, Robert Searles, Rebecca L. Smith, Stephen E. Spurgeon, Tyler Sweeney, Ronan T. Swords, Aashis Thapa, Karina Thiel-Klare, Elie Traer, Jake Wagner, Beth Wilmot, Joelle Wolf, Guanming Wu, Amy Yates, Haijiao Zhang, Christopher R. Cogle, Robert H. Collins, Michael W. Deininger, Christopher S. Hourigan, Craig T. Jordan, Tara L. Lin, Micaela E. Martinez, Rachel R. Pallapati, Daniel A. Pollyea, Anthony D. Pomicter, Justin M. Watts, Scott J. Weir, Brian J. Druker, Shannon K. McWeeney, Jeffrey W. Tyner
Summary: This report presents findings from a large cohort of AML patients, combining genomic, transcriptomic, and clinical data to uncover associations between drug sensitivity, cell differentiation state, and patient survival prediction.
Article
Biochemical Research Methods
Sara J. C. Gosline, Cristina Tognon, Michael Nestor, Sunil Joshi, Rucha Modak, Alisa Damnernsawad, Camilo Posso, Jamie Moon, Joshua R. Hansen, Chelsea Hutchinson-Bunch, James C. Pino, Marina A. Gritsenko, Karl K. Weitz, Elie Traer, Jeffrey Tyner, Brian Druker, Anupriya Agarwal, Paul Piehowski, Jason E. McDermott, Karin Rodland
Summary: This study describes a systematic, multi-omic approach to evaluate proteomic signatures of drug response in AML. The study demonstrates strong promise for proteomics-based patient stratification to assess drug sensitivity in AML.
CLINICAL PROTEOMICS
(2022)
Editorial Material
Biochemical Research Methods
Sunil K. Joshi, Cristina E. Tognon, Brian J. Druker, Karin D. Rodland
EXPERT REVIEW OF PROTEOMICS
(2022)
Letter
Hematology
Sunil K. Joshi, Janet Pittsenbarger, Vanessa E. Kennedy, Cheryl A. C. Peretz, Alexander E. Perl, Catherine C. Smith, Jeffrey W. Tyner, Brian J. Druker, Elie Traer
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Biochemical Research Methods
Atif Khurshid Wani, Chirag Chopra, Daljeet Singh Dhanjal, Nahid Akhtar, Himanshu Singh, Poorvi Bhau, Anjuvan Singh, Varun Sharma, Rafael Silvio Bonilha Pinheiro, Juliana Heloisa Pine Americo-Pinheiro, Reena Singh
Summary: Zoonotic viral infections pose significant threats to global public health. Understanding the origins and dynamics of these infections is crucial for prevention and management of future outbreaks. Metagenomics is a powerful tool for studying the diversity of viral populations and potential zoonotic events.
JOURNAL OF VIROLOGICAL METHODS
(2024)
Article
Biochemical Research Methods
Michel V. F. Sucupira, Ana P. C. Argondizzo, Mariana Miguez, Anna E. de Araujo, Leila B. R. Silva, Marcelle B. Mello, Christiane F. S. Marques, Danielle Brito Cunha, Renata C. Bastos, Vanessa S. de Paula, Luciane A. Amado Leon
Summary: This study focuses on improving the purification, solubility, and protein expression levels of recombinant VP1-2A, a hepatitis A virus (HAV) structural protein with immunogenic activity. The results show that the modified approach successfully produces biologically active HAV VP1-2A, which can be used as a diagnostic tool for HAV infection.
JOURNAL OF VIROLOGICAL METHODS
(2024)
Article
Biochemical Research Methods
Arun K. Dhar, Roberto Cruz-Flores, Hung N. Mai, Janet Warg
Summary: A sensitive and robust TaqMan PCR method for detecting IHHNV in three commercially important shrimp species was developed and compared with other published methods. Multiple primer/probe sets, including qIH-Fw/qIH-Rv and 3144F/3232R, are recommended for the detection of IHHNV. These findings are valuable for large-scale screening of shrimp using a TaqMan real-time PCR assay.
JOURNAL OF VIROLOGICAL METHODS
(2024)
Article
Biochemical Research Methods
Kemal Mehinagic, Matthias Liniger, Maksym Samoilenko, Nick Soltermann, Markus Gerber, Nicolas Ruggli
Summary: A plasmid-based reporter assay has been developed for sensitive detection and titration of infectious African swine fever virus (ASFV). This novel method allows accurate measurement of ASFV titers and is applicable to ASFV of different genotypes, virulence, and sources.
JOURNAL OF VIROLOGICAL METHODS
(2024)
Article
Biochemical Research Methods
Jan Van Slambrouck, Charlotte Schoenaers, Lies Laenen, Xin Jin, Kurt Beuselinck, Ann Verdonck, Joost Wauters, Geert Molenberghs, Bart M. Vanaudenaerde, Robin Vos, Peter Mombaerts, Katrien Lagrou, Laurens J. Ceulemans
Summary: The ability to detect SARS-CoV-2 RNA or antigen in BAL fluid samples using point-of-care tests (POCTs) can reduce the risk of developing severe COVID-19 after lung transplantation.
JOURNAL OF VIROLOGICAL METHODS
(2024)