Article
Chemistry, Medicinal
Natalie Losada, Francesc X. Ruiz, Francesca Curreli, Kevin Gruber, Alyssa Pilch, Kalyan Das, Asim K. Debnath, Eddy Arnold
Summary: This study focuses on compounds (NBD derivatives) originally developed to bind to HIV-1 gp120, some of which inhibit RT. Crystal structures of three NBD compounds in complex with HIV-1 RT have been determined, correlating with RT enzyme inhibition and antiviral activity, to develop structure-activity relationships. Two lead compounds, NBD-14189 and NBD-14270, show potent antiviral activity and low cytotoxicity.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Yik Lim Kok, Valentina Vongrad, Sandra E. Chaudron, Mohaned Shilaih, Christine Leemann, Kathrin Neumann, Katharina Kusejko, Francesca Di Giallonardo, Herbert Kuster, Dominique L. Braun, Roger D. Kouyos, Huldrych F. Gunthard, Karin J. Metzner
Summary: Characteristics of HIV-1 integration sites are established as early as during primary infection and are found in both resting and activated CD4(+) T cells. HIV-1 integration sites preferentially occur in specific genes and highly expressed genes, regardless of the activation state of CD4(+) T cells. The preference for cancer-related genes is more prominent at later stages of HIV-1 infection.
Review
Cell Biology
Masyelly Rojas, Patricia Luz-Crawford, Ricardo Soto-Rifo, Sebastian Reyes-Cerpa, Daniela Toro-Ascuy
Summary: Human immunodeficiency virus type 1 (HIV-1) infection leads to the generation of latent viral reservoirs, associated with chronic immune activation and inflammation, where macrophages play a crucial role in balancing the IFN/ISG signaling network.
Article
Biochemistry & Molecular Biology
Kolin M. Clark, Josh G. Kim, Qiankun Wang, Hongbo Gao, Rachel M. Presti, Liang Shan
Summary: The sensitization of the CARD8 inflammasome to non-nucleoside reverse transcriptase inhibitors (NNRTIs) can be achieved through chemical inhibition of the negative regulator DPP9. The DPP9 inhibitor Val-boroPro (VbP) can kill HIV-1-infected cells without NNRTIs and synergize with NNRTIs to promote clearance of infected cells. This offers a promising strategy for enhancing NNRTI efficacy in eliminating HIV-1 reservoirs.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Microbiology
Lijun Cong, Scott M. Sugden, Pascal Leclair, Chinten James Lim, Tram N. Q. Pham, Eric A. Cohen
Summary: The HIV-1 accessory protein Vpu modulates macrophage infection by downregulating CD47 expression on infected cells, promoting phagocytosis. This mechanism enhances the susceptibility of macrophages to viral infection and allows for efficient infection by weakly macrophage-tropic virus strains. The findings provide new insights into intercellular transmission of HIV-1 to macrophages and have implications for viral reservoir establishment and early dissemination in vivo.
Article
Multidisciplinary Sciences
Marcela Pavova, Paul Eduardo Reyes-Gutierrez, Jaroslav Kozak, Juraj Dobias, Yevgen Yurenko, Martin Lepsik, Filip Teply, Jan Weber
Summary: G-quadruplexes, which are nucleic acids containing quartets of guanines, play a role in regulating gene transcription. Helquat-based compounds have been identified as a new class of anti-HIV-1 inhibitors that can stabilize G-quadruplexes in the HIV-1 long-terminal repeat sequence. This discovery can contribute to the rational design of inhibitors targeting G-quadruplexes in HIV-1.
SCIENTIFIC REPORTS
(2023)
Article
Multidisciplinary Sciences
Viviana Cobos Jimenez, Aviva Geretz, Andrey Tokarev, Philip K. Ehrenberg, Selase Deletsu, Kawthar Machmach, Prakriti Mudvari, J. Natalie Howard, Amanda Zelkoski, Dominic Paquin-Proulx, Gregory Q. Del Prete, Caroline Subra, Eli A. Boritz, Alberto Bosque, Rasmi Thomas, Diane L. Bolton
Summary: AP-1 transcription factor plays an important role in latent HIV-1 infection and reactivation. Inhibiting AP-1 may be a potential therapeutic approach to limit HIV-1 reservoirs.
Article
Pharmacology & Pharmacy
Hans Kek, Annemarie Laumaea, Srihari Parise, Pantelis Poumbourios, Anna C. Hearps, Anthony Jaworowski
Summary: The study found potential differences in epitope expression on HIV-infected macrophages and T cells. Infected macrophages were more susceptible to opsonization by certain antibodies, while infected T cells were more susceptible to opsonization by different antibodies. Neutralizing antibodies were relatively ineffective at opsonizing Env on the surface of infected cells compared to cell-free virions.
ANTIVIRAL RESEARCH
(2021)
Article
Immunology
Jingjing Cao, Lili Ji, Yanxia Zhan, Xia Shao, Pengcheng Xu, Boting Wu, Pu Chen, Luya Cheng, Xibing Zhuang, Yang Ou, Fanli Hua, Lihua Sun, Feng Li, Hao Chen, Zhaocai Zhou, Yunfeng Cheng
Summary: This study reveals the critical role of MST4 kinase in ITP and identifies it as a potential therapeutic target for refractory ITP.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Article
Virology
Marta Calado, David Pires, Carolina Conceicao, Rita Ferreira, Quirina Santos-Costa, Elsa Anes, Jose Miguel Azevedo-Pereira
Summary: Macrophages and dendritic cells are important for the spread of HIV to CD4+ T lymphocytes during acute infection and constitute a persistently infected reservoir during chronic infection. Cell-to-cell contact triggers the production of infectious viral particles, contributing to viral replication. The phenotypic characteristics of HIV isolates do not correlate with their spread or the difference between HIV-1 and HIV-2 in terms of cis- or trans-infection. Understanding the cell-to-cell spread of HIV is critical for developing new therapeutic and vaccine approaches.
Article
Immunology
Vincent H. Wu, Jayme M. L. Nordin, Son Nguyen, Jaimy Joy, Felicity Mampe, Perla M. del Rio Estrada, Fernanda Torres-Ruiz, Mauricio Gonzalez-Navarro, Yara Andrea Luna-Villalobos, Santiago Avila-Rios, Gustavo Reyes-Teran, Pablo Tebas, Luis J. Montaner, Katharine J. Bar, Laura A. Vella, Michael R. Betts
Summary: In this study, a single-cell strategy was developed to define the HIV-infected memory CD4(+) T cell reservoir in ART-treated people living with HIV (ART-PLWH) using integrated accessible proviral DNA, epigenetic and cell surface protein profiling. The study identified a profound reservoir heterogeneity within and between ART-PLWH, characterized by new and known surface markers within memory CD4(+) T cell subsets. Furthermore, new epigenetic profiles and transcription factor motifs enriched in HIV-infected cells were uncovered, suggesting a potential for reactivation during ART treatment. These findings establish an initial multiomic atlas for targeted reservoir elimination strategies.
Article
Multidisciplinary Sciences
Jeremy Dufloo, Cyril Planchais, Stephane Fremont, Valerie Lorin, Florence Guivel-Benhassine, Karl Stefic, Nicoletta Casartelli, Arnaud Echard, Philippe Roingeard, Hugo Mouquet, Olivier Schwartz, Timothee Bruel
Summary: Researchers have found that broadly neutralizing antibodies (bNAbs) can not only neutralize HIV-1, but also block the release of viral particles by trapping them on the surface of infected cells. This study reveals an additional antiviral mechanism of bNAbs.
NATURE COMMUNICATIONS
(2022)
Article
Virology
Jingliang Chen, Yaozu He, Huolin Zhong, Fengyu Hu, Yonghong Li, Yeyang Zhang, Xia Zhang, Weiyin Lin, Quanmin Li, Feilong Xu, Shaozhen Chen, Hui Zhang, Weiping Cai, Linghua Li
Summary: Some HIV-infected individuals receiving antiretroviral therapy (ART) develop low-level viremia (LLV), which is associated with virologic failure. The characteristics of CD4+ T cells in LLV are largely unknown. In this study, we analyzed the transcriptome profiling of CD4+ T cells from healthy controls, HIV-infected patients with virologic suppression, and those with LLV. We found that CD4+ T cells in LLV expressed higher levels of Th1 signature transcription factors, toll-like receptors, anti-HIV entry chemokines, and antiIL-1& beta; factors compared to virologic suppression. We also identified pathways that could promote HIV-1 replication in LLV. Finally, we evaluated the effects of upregulated transcription factors on HIV-1 promoter activity and found that CXXC5 increased, while SOX5 suppressed HIV-1 transcription.
Article
Biochemistry & Molecular Biology
Samir Amrane, Chloe Jaubert, Amina Bedrat, Tiffany Rundstadler, Patricia Recordon-Pinson, Cindy Aknin, Aurore Guedin, Aurore De Rache, Laura Bartolucci, Ibra Diene, Frederic Lemoine, Olivier Gascuel, Genevieve Pratviel, Jean-Louis Mergny, Marie-Line Andreola
Summary: The formation of G-quadruplex structures during HIV-1 infection plays a crucial role in viral replication and processing of viral RNA genome. The use of G4-binders has shown to efficiently inhibit HIV-1 infectivity.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Microbiology
Shima Shahbaz, Isobel Okoye, Gregg Blevins, Shokrollah Elahi
Summary: CD8(+) T cells play an important role in chronic viral infections, but the expression of CD73 is compromised and its function impaired in HIV infection. CD73 expression is decreased in HIV-infected individuals at both cell surface and gene levels. CD73(+) T cells exhibit functional impairments while showing enhanced migration capabilities.
Article
Immunology
Beiqing Wu, Jianhui Liu, Runze Zhao, Yuju Li, Justin Peer, Alexander L. Braun, Lixia Zhao, Yi Wang, Zenghan Tong, Yunlong Huang, Jialin C. Zheng
JOURNAL OF NEUROINFLAMMATION
(2018)
Article
Immunology
Miao He, Hainan Zhang, Yuju Li, Guangshun Wang, Beisha Tang, Jeffrey Zhao, Yunlong Huang, Jialin Zheng
FRONTIERS IN IMMUNOLOGY
(2018)
Article
Cell Biology
Yunlong Huang, Yuju Li, Hainan Zhang, Runze Zhao, Ran Jing, Yinghua Xu, Miao He, Justin Peer, Yeong C. Kim, Jiangtao Luo, Zenghan Tong, Jialin Zheng
Article
Neurosciences
Miao He, Hainan Zhang, Yuju Li, Changhai Tian, Beisha Tang, Yunlong Huang, Jialin Zheng
NEUROSCIENCE LETTERS
(2019)
Article
Neurosciences
Kangmu Ma, Xiaobei Deng, Xiaohuan Xia, Zhaohuan Fan, Xinrui Qi, Yongxiang Wang, Yuju Li, Yizhao Ma, Qiang Chen, Hui Peng, Jianqing Ding, Chunhong Li, Yunlong Huang, Changhai Tian, Jialin C. Zheng
TRANSLATIONAL NEURODEGENERATION
(2018)
Article
Neurosciences
Yizhao Ma, Kaizhe Wang, Jiabin Pan, Zhaohuan Fan, Changhai Tian, Xiaobei Deng, Kangmu Ma, Xiaohuan Xia, Yunlong Huang, Jialin C. Zheng
NEUROBIOLOGY OF DISEASE
(2019)
Article
Neurosciences
Ge Gao, Shu Zhao, Xiaohuan Xia, Chunhong Li, Congcong Li, Chenhui Ji, Shiyang Sheng, Yalin Tang, Jie Zhu, Yi Wang, Yunlong Huang, Jialin C. Zheng
FRONTIERS IN CELLULAR NEUROSCIENCE
(2019)
Article
Pharmacology & Pharmacy
Runze Zhao, Yuju Li, Santhi Gorantla, Larisa Y. Poluektova, Hai Lin, Fengtong Gao, Hongyun Wang, Jeffrey Zhao, Jialin C. Zheng, Yunlong Huang
ANTIVIRAL RESEARCH
(2019)
Article
Cell Biology
Yizhao Ma, Chunhong Li, Yunlong Huang, Yi Wang, Xiaohuan Xia, Jialin C. Zheng
CELL COMMUNICATION AND SIGNALING
(2019)
Article
Immunology
Jianhui Liu, Yuju Li, Xiaohuan Xia, Xiaoyu Yang, Runze Zhao, Justin Peer, Hongyun Wang, Zenghan Tong, Fengtong Gao, Hai Lin, Beiqing Wu, Yunlong Huang, Jialin C. Zheng
JOURNAL OF NEUROIMMUNOLOGY
(2019)
Meeting Abstract
Neurosciences
Miao He, Hainan Zhang, Yuju Li, Guangshun Wang, Beisha Tang, Jeffrey Zhao, Yunlong Huang, Jialin Zheng
JOURNAL OF NEUROVIROLOGY
(2018)
Meeting Abstract
Neurosciences
Runze Zhao, Yunlong Huang, Jialin Zheng
JOURNAL OF NEUROVIROLOGY
(2018)
Meeting Abstract
Neurosciences
Miao He, Hainan Zhang, Yuju Li, Guangshun Wang, Beisha Tang, Jeffrey Zhao, Yunlong Huang, Jialin Zheng
JOURNAL OF NEUROIMMUNE PHARMACOLOGY
(2018)
Meeting Abstract
Neurosciences
Runze Zhao, Yunlong Huang, Jialin Zheng
JOURNAL OF NEUROIMMUNE PHARMACOLOGY
(2018)
Article
Immunology
Yi Wang, Yuju Li, Runze Zhao, Beiqing Wu, Blaise Lanoha, Zenghan Tong, Justin Peer, Jianhui Liu, Huangui Xiong, Yunlong Huang, Jialin Zheng
BRAIN BEHAVIOR AND IMMUNITY
(2017)