Article
Biochemical Research Methods
Cong Wang, Chunjing Chen, Zhenrui Pan, Yaohui He, Zhanming Zhang, Rongdiao Liu, Yuhua Xue, Qiang Zhou, Xiang Gao
Summary: Brd4 has attracted significant attention as a potential drug target due to its involvement in oncogenesis, inflammation, and HIV-1 transcription. Mass spectrometry-based quantitative proteomics identified 352 proteins that interact with CDK9, among which the increased bindings of HSP90 and CDC37 were particularly notable. The findings advance our understanding of how the HSP90-CDC37-P-TEFb complex regulates HIV-1 latency.
JOURNAL OF PROTEOME RESEARCH
(2023)
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
Microbiology
Ariane Zutz, Lin Chen, Franziska Sippl, Andreas Humpe, Christian Schoelz
Summary: The study focused on screening latent reservoirs in HIV-1 infected individuals and identified two novel compounds with high reactivation efficiency and low toxicity as potential new treatment options for reversing latency.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Review
Virology
Thanarat Salahong, Christian Schwartz, Rungroch Sungthong
Summary: A key challenge in AIDS therapy is the evasive nature of HIV-1 and its latency, leading to the proposal of the "Shock and Kill" strategy to eliminate latent HIV-1-infected cell reservoirs. This strategy involves two crucial steps: reactivating HIV-1 and enhancing immune responses to destroy infected cells.
Article
Virology
Terry L. Hafer, Abby Felton, Yennifer Delgado, Harini Srinivasan, Michael Emerman
Summary: This study aimed to investigate whether host factors required for HIV-1 replication also play a role in latency reversal. By using a CRISPR gene library and analyzing RNA sequencing data, several key HIV-1 dependency factors were identified, with CCNT1 being the most crucial factor for latency reactivation.
Article
Immunology
Lesley R. de Armas, Christina Gavegnano, Suresh Pallikkuth, Stefano Rinaldi, Li Pan, Emilie Battivelli, Eric Verdin, Ramzi T. Younis, Rajendra Pahwa, Sion L. Williams, Raymond F. Schinazi, Savita Pahwa
Summary: The study used the dual reporter virus HIVGKO to investigate latency establishment and maintenance in CD4(+) T cells, and analyzed latently infected cells using single cell technologies. The research found that JAK1/2 inhibitors could reduce HIV infection events and block HIV reactivation from latent cells.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Plant Sciences
Haitao Zhang, Jinfeng Cai, Chunna Li, Lisi Deng, Hongqiong Zhu, Ting Huang, Jiacong Zhao, Jiasheng Zhou, Kai Deng, Zhongsi Hong, Jinyu Xia
Summary: This study found that wogonin can suppress latent HIV-1 reactivation by inhibiting the expression of histone acetyltransferase p300 and decreasing the crotonylation of histone H3/H4 in the HIV-1 promoter region. This discovery holds promising significance for future applications in HIV-1 functional cure.
Article
Virology
Ayaka Washizaki, Megumi Murata, Yohei Seki, Masayuki Kikumori, Yinpui Tang, Weikeat Tan, Nadita P. Wardani, Kazuhiro Irie, Hirofumi Akari
Summary: The study found that a novel PKC activator, 10MA-1, combined with the inhibitor JQ1 can strongly and synergistically reactivate latently infected HIV, with JQ1 effectively suppressing side effects induced by 10MA-1.
Review
Pharmacology & Pharmacy
Matthew Weichseldorfer, Marvin Reitz, Olga S. Latinovic
Summary: Combined antiretroviral therapy (cART) is widely recommended for controlling HIV-1 replication and improving the quality of life of infected individuals. However, latent infected cells remain a major barrier to treatment efficacy in the long term.
Article
Virology
Lendel Correia da Costa, Larissa Maciel Bomfim, Uilla Victoria Torres Dittz, Camila de Almeida Velozo, Rodrigo Delvecchio da Cunha, Amilcar Tanuri
Summary: This study successfully blocked the reactivation of HIV-1 using the CRISPR/dCas9-KRAB platform, and identified useful hotspot sequences for treatment design.
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.
Article
Clinical Neurology
Angel Lin, Weam Othman Elbezanti, Alexis Schirling, Adel Ahmed, Rachel Van Duyne, Simon Cocklin, Zachary Klase
Summary: The HIV-1 pandemic poses a significant challenge to the field of medicine, with no cure yet found. Research has identified that the benzodiazepine Alprazolam could be an ideal candidate for latency reversal as it inhibits the transcription factor RUNX1 and increases STAT5 activation, potentially playing a positive role in addressing neuroinflammation associated with neuroHIV-1.
FRONTIERS IN NEUROLOGY
(2021)
Article
Virology
Erich J. Baker, Kelly Hughes, Tatianna Travieso, Mary E. Klotman, Maria Blasi
Summary: Anti-retroviral therapy (ART) has significantly reduced HIV-related morbidity and mortality. However, the long-term persistence of latent viral reservoirs capable of reactivation remains a challenge. This study explores the establishment of HIV-1 latency in renal epithelial cells and finds that current latency reversing agents (LRAs) have limited effectiveness in reactivating HIV-1 in these cells. Further research on LRAs in non-T cells is needed to assess their suitability for a sterilizing cure strategy.
JOURNAL OF VIROLOGY
(2022)
Article
Virology
Michelle E. Wong, Chad J. Johnson, Anna C. Hearps, Anthony Jaworowski
Summary: In this study, a robust experimental model was established to quantify and investigate HIV reactivation in latently infected macrophages, showing that different macrophage phenotypes, cellular and tissue environments influence HIV reactivation. Additionally, the study demonstrated that certain latency-reversing agents may have different effects on latently infected macrophages compared to T cells, suggesting the need for dedicated strategies to target these populations in vivo.
JOURNAL OF VIROLOGY
(2021)
Article
Chemistry, Medicinal
Wensheng Yu, James Fells, Dane Clausen, Jian Liu, Daniel J. Klein, C. Christine Chung, Robert W. Myers, Jin Wu, Guoxin Wu, Bonnie J. Howell, Richard J. O. Barnard, Joseph Kozlowski
Summary: A series of unique macrocyclic HDACs 1, 2, and 3 selective inhibitors were identified, showing good enzymatic activity and high selectivity over HDACs 6 and 8. Compounds 25 and 26 stood out as leads with low double-digit nM EC(50)s in the 2C4 cell-based HIV latency reactivation assay, but the PK profiles of these macrocyclic HDAC inhibitors still needed improvement.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Organic
Xiaoming Ma, Xiaofeng Zhang, John Mark Awad, Guoshu Xie, Weiqi Qiu, Rachel E. Muriph, Wei Zhang
TETRAHEDRON LETTERS
(2020)
Article
Chemistry, Physical
Chuan Tian, Koushik Kasavajhala, Kellon A. A. Belfon, Lauren Raguette, He Huang, Angela N. Migues, John Bickel, Yuzhang Wang, Jorge Pincay, Qin Wu, Carlos Simmerling
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2020)
Article
Chemistry, Organic
Xiaoming Ma, Suzhi Meng, Xiaofeng Zhang, Qiang Zhang, Shenghu Yan, Yue Zhang, Wei Zhang
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2020)
Article
Cell Biology
Meera Singh, Sumanun Suwunnakorn, Sydney R. Simpson, Emily A. Weber, Vir B. Singh, Pawel Kalinski, Sanjay B. Maggirwar
Summary: Activated platelets form complexes with monocytes, inhibiting the development of functional dendritic cells and decreasing immune responses to HIV antigens. Disruption of these complexes with antiplatelet drugs may enhance immunization against HIV.
JOURNAL OF LEUKOCYTE BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Dawei Zhou, Tsuyoshi Hayashi, Maxime Jean, Weili Kong, Guillaume Fiches, Ayan Biswas, Shuai Liu, Hailemichael O. Yosief, Xiaofeng Zhang, Jay Bradner, Jun Qi, Wei Zhang, Netty Santoso, Jian Zhu
Article
Hematology
Sydney R. Simpson, Meera Singh, Stephen Dewhurst, Giovanni Schifitto, Sanjay B. Maggirwar
Article
Virology
Diana M. Dunn, Irene Rodriguez-Sanchez, Xenia Schafer, Joshua Munger
Summary: Human cytomegalovirus (HCMV) infection modulates cellular metabolism by relying on specific CaMKK and AMPK isoforms to support glycolytic activation and productive infection.
JOURNAL OF VIROLOGY
(2021)
Article
Immunology
Sergio Castro-Gonzalez, Sydney Simpson, Yuhang Shi, Yuexuan Chen, Jared Benjamin, Ruth Serra-Moreno
Summary: Ubiquitination plays a critical role in various aspects of HIV replication, influencing factors such as activity, localization, and stability. It also impacts the interactions between HIV and the cellular environment, specifically with regards to autophagy and apoptosis.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Chemistry, Organic
Wensheng Zhang, Yan Li, Hongyan Zhou, Xiaoli Su, Xiaofeng Zhang, Wei Zhang
Summary: This method involves the reductive amination of o-azidobenzaldehydes and aryl amines followed by the Staudinger-aza-Wittig reaction with CS2 to synthesize 3-aryl-3,4-dihydroquinazoline-2(1H)-thiones in one pot and two steps.
TETRAHEDRON LETTERS
(2021)
Article
Chemistry, Multidisciplinary
Xiaofeng Zhang, Miao Liu, Desheng Zhan, Manpreet Kaur, Jerry P. Jasinski, Wei Zhang
Summary: A three-component reaction of nonstabilized azomethine ylides derived from alpha-C-H functionalization of tetrahydroisoquinoline has been developed for the regio- and diastereoselective synthesis of spirooxindole-pyrrolidines. This method provides a pot, atom and step economy (PASE) approach for preparing spiro-heterocyclic compounds with biological interest, using readily available cyclic amines, aryl aldehydes, and olefinic oxindoles.
NEW JOURNAL OF CHEMISTRY
(2022)
Article
Chemistry, Organic
Juan Lu, Bin Yao, Desheng Zhan, Zhuo Sun, Yun Ji, Xiaofeng Zhang
Summary: A novel four-component reaction has been developed for the synthesis of diastereoselective-ly spirooxindolepyrrolothiazoles. The reaction involves sequential N,S-acetalation of aldehydes with cysteine and decarboxylative [3 + 2] cycloaddition with olefinic oxindoles. The use of EtOH as solvent and the release of only CO2 and H2O as side products make this approach favorable in green chemistry metrics analysis.
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Wensheng Zhang, Wei Zheng, Guoqiang Zuo, Xiaole Li, Xiaofeng Zhang, Wei Zhang
Summary: A one-pot synthesis for the preparation of 1,2,3,4-tetrahydroacridines involving a Zr(iv)-catalyzed Mannich reaction of o-azidobenzaldehydes and arylamines with cycloketones, followed by aza-Witting cyclization and deaminative aromatization, is developed. This method can be extended for the synthesis of cyclohepta[b]quinolines.
NEW JOURNAL OF CHEMISTRY
(2022)
Article
Chemistry, Organic
Xiaofeng Zhang, Xiaoming Ma, Wei Zhang
Summary: This article highlights recent work on the development of alpha-amino acid-based [3 + 2] cycloaddition reactions of N-H-type AMYs in multicomponent, one-pot, and stepwise reactions for the synthesis of diverse heterocycles related to some bioactive compounds and natural products.
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Oncology
Hiroto Ohguchi, Paul M. C. Park, Tingjian Wang, Berkley E. Gryder, Daisuke Ogiya, Keiji Kurata, Xiaofeng Zhang, Deyao Li, Chengkui Pei, Takeshi Masuda, Catrine Johansson, Virangika K. Wimalasena, Yong Kim, Shinjiro Hino, Shingo Usuki, Yawara Kawano, Mehmet K. Samur, Yu-Tzu Tai, Nikhil C. Munshi, Masao Matsuoka, Sumio Ohtsuki, Mitsuyoshi Nakao, Takashi Minami, Shannon Lauberth, Javed Khan, Udo Oppermann, Adam D. Durbin, Kenneth C. Anderson, Teru Hideshima, Jun Qi
Summary: The study revealed that KDM5A can interact with the P-TEFb complex and cooperate with MYC to control MYC-targeted genes in multiple myeloma cells. They developed a KDM5 inhibitor, JQKD82, which paradoxically increases H3K4me3 but inhibits downstream MYC-driven transcriptional output in vitro and in vivo.
BLOOD CANCER DISCOVERY
(2021)
Article
Chemistry, Multidisciplinary
Xiaoming Ma, Xiaofeng Zhang, John Mark Awad, Guoshu Xie, Weiqi Qiu, Wei Zhang