Article
Biochemistry & Molecular Biology
Mario Cano-Munoz, Julie Lucas, Li-Yun Lin, Samuele Cesaro, Christiane Moog, Francisco Conejero-Lara
Summary: This study identified the vulnerability of the gp41 C-terminal heptad repeat to inhibition and demonstrated that engineering stable miniproteins can enhance inhibitory potency against HIV-1. These findings have implications in the development of new strategies to inhibit HIV targeting the gp41 CHR region.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Xiaoqian Xin, Yifeng Liu, Lei Guo, Hui Wang, Daiqiang Lu, Yaotian Chang, Mingming Wan, Yong Zhang, Yaming Shan, Qiao Zhang, Xiaowen Liu, Feng Gao
Summary: The HIV virus poses a major threat to human health with over 84 million people infected. Developing a vaccine has been challenging due to the high genetic variation of the virus. However, a new HIV-1 envelope glycoprotein nanoparticle vaccine has been designed using amphiphilic polymers, which shows potent and broad neutralizing activities against multiple HIV-1 subtypes. Additionally, this vaccine remains stable under different storage conditions and can potentially be applied to other protein-based vaccines.
Article
Virology
Alba Torrents de la Pena, Ivan del Moral Sanchez, Judith A. Burger, Ilja Bontjer, Gozde Isik, Dirk Eggink, Marit J. van Gils, Rogier W. Sanders
Summary: Directed virus evolution was used to enhance the stability of the HIV-1 envelope glycoprotein (Env) trimer. By deliberately destabilizing the interface between Env subunits, compensatory mutations were identified in specific Env regions, indicating a potential to strengthen intersubunit interactions and enhance trimer stability. This study sheds light on the structural mechanisms involved in Env trimer stability, which can inform future immunogen design.
JOURNAL OF VIROLOGY
(2021)
Article
Virology
Ayna Alfadhli, CeAnn Romanaggi, Robin Lid Barklis, Eric Barklis
Summary: Trimers of HIV-1 envelope protein are crucial for the virus life cycle, and we studied a panel of Env variants to understand their activities. We found that CT truncations or baseplate mutations in Env led to defective replication in restrictive cells. We also identified determinants in HIV-1 sensitivity to amphotericin and characterized variants that escape amphotericin inhibition through CT cleavage by viral protease. Additionally, we showed that full-length, his tagged Env can oligomerize with CT truncations that delete parts of the baseplate, host protein binding sites, and trafficking signals. Our study provides new insights into the structure, interactions, and functions of the HIV-1 CT.
Review
Virology
Tianshu Xiao, Yongfei Cai, Bing Chen
Summary: HIV-1 infection begins with virion attachment to host cell membrane through Env, binding to receptors CD4 and coreceptors CCR5/CXCR4; understanding the structural biology of HIV-1 Env aids in designing antiviral therapeutics targeting viral entry.
Article
Biochemistry & Molecular Biology
Francesca Curreli, Young D. Kwon, Isabella Nicolau, Giancarla Burgos, Andrea Altieri, Alexander V. Kurkin, Raffaello Verardi, Peter D. Kwong, Asim K. Debnath
Summary: As part of the effort to discover drugs targeting HIV-1 entry, this study investigates the antiviral activity and crystal structures of two novel inhibitors in complex with a gp120 core. The results show that NBD-14204 exhibits better antiviral activity and sensitivity to certain mutants, making it a promising compound for further optimization.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Virology
Aurelie Drouin, Julie Migraine, Marie-Alice Durand, Alain Moreau, Julien Burlaud-Gaillard, Maxime Beretta, Philippe Roingeard, Melanie Bouvin-Pley, Martine Braibant
Summary: The cellular factor IFITM3 reduces HIV-1 infectivity through an unclear mechanism. IFITM3 interacts with Env of sensitive viruses, inducing conformational changes that decrease viral infectivity, but this antiviral action is modulated by the nature of Env, particularly the V1V2 and V3 loops, which may escape this interaction after processing in the Golgi apparatus.
JOURNAL OF VIROLOGY
(2021)
Article
Microbiology
Yuta Hikichi, Rachel Van Duyne, Phuong Pham, Jennifer L. Groebner, Ann Wiegand, John W. Mellors, Mary F. Kearney, Eric O. Freed
Summary: The presence of mutations in the HIV-1 envelope glycoprotein (Env) can lead to reduced susceptibility to multiple classes of antiretroviral drugs (ARVs) and may contribute to virological failure in patients. The accumulation of Env mutations in individuals failing integrase inhibitor therapy suggests a possible mechanism for drug resistance development without mutations in target genes. Understanding how Env mutations affect drug resistance may influence therapeutic strategies for ARV-treated patients.
Article
Virology
Nicholas Weaver, Jason Hammonds, Lingmei Ding, Grigoriy Lerner, Krista Dienger-Stambaugh, Paul Spearman
Summary: The molecular motor protein KIF16B regulates the outward sorting step involved in human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trafficking, limiting lysosomal degradation and enhancing particle incorporation. The absence of KIF16B reduces Env expression on cell surface, leading to a decrease in Env incorporation into particles and particle infectivity. HIV-1 replication is substantially reduced in KIF16B knockout cells.
JOURNAL OF VIROLOGY
(2023)
Article
Chemistry, Analytical
Nicole A. Schneck, Alison L. Vinitsky, Vera B. Ivleva, Xiangchun Wang, Daniel B. Gowetski, Q. Paula Lei
Summary: This paper introduces a new RPLC-UV method coupled with reduction to determine the percentage of uncleaved gp140 relative to the cleaved gp120 and gp41 subunits. This approach has been successfully applied to support the development of Env vaccine candidates.
ANALYTICAL METHODS
(2021)
Article
Biochemistry & Molecular Biology
Evan M. Cale, Jefferson Driscoll, Myungjin Lee, Jason Gorman, Tongqing Zhou, Maolin Lu, Hui Geng, Yen-Ting Lai, Gwo-Yu Chuang, Nicole A. Doria-Rose, Walther Mothes, Peter D. Kwong, John R. Mascola
Summary: This study reveals the antigenic differences between different conformational states of HIV-1 envelope trimer (Env) and explores the structural insights of State 1, which is not well understood. The results show consistent but minor binding differences between State 1 and State 2 of HIV-1 Env, and a more than 10-fold difference in binding compared to State 3.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Cell Biology
Annemarie Laumaea, Lorie Marchitto, Shilei Ding, Guillaume Beaudoin-Bussieres, Jeremie Prevost, Romain Gasser, Debashree Chatterjee, Gabrielle Gendron-Lepage, Halima Medjahed, Hung-Ching Chen, Amos B. Smith III, Haitao Ding, John C. Kappes, Beatrice H. Hahn, Frank Kirchhoff, Jonathan Richard, Ralf Duerr, Andres Finzi
Summary: The conformation of HIV-1 envelope (Env) determines the susceptibility of infected CD4(+) T cells to antibody-dependent cellular cytotoxicity (ADCC). The downregulation of CD4 on infected macrophages by Nef, Vpu, and Env has a lesser impact on Env conformation and ADCC sensitivity compared to CD4(+) T cells. However, treatment of infected macrophages with small CD4 mimetics exposes vulnerable CD4-induced Env epitopes and sensitizes them to ADCC.
Article
Virology
Tarana A. Mangukia, Joy Ramielle L. Santos, Weijie Sun, Dominik Cesarz, Carlos D. Ortiz Hidalgo, Marcelo Marcet-Palacios
Summary: The molecular structure of HIV-1 is closely related to its entry mechanism. The virus lacks a matrix (MA) shell in a specific region and during viral maturation, Env proteins cluster in this region. This cluster formation in the region without the MA shell is likely to play a crucial role in viral entry.
Article
Multidisciplinary Sciences
Jeremie Prevost, Yaozong Chen, Fei Zhou, William D. Tolbert, Romain Gasser, Halima Medjahed, Manon Nayrac, Dung N. Nguyen, Suneetha Gottumukkala, Ann J. Hessell, Venigalla B. Rao, Edwin Pozharski, Rick K. Huang, Doreen Matthies, Andres Finzi, Marzena Pazgier
Summary: Resistance to the HIV-1 entry inhibitor temsavir is not solely determined by residue 375, but also involves other residues within the gp120 inner domain layers. The resistance is mediated by crosstalk between residue 375 and the inner domain layers. Additionally, temsavir has the ability to adjust its binding mode to accommodate changes in Env conformation, contributing to its broad antiviral activity.
NATURE COMMUNICATIONS
(2023)
Article
Microbiology
Peng Zhang, Alice L. Kwon, Christina Guzzo, Qingbo Liu, Hana Schmeisser, Huiyi Miao, Yin Lin, Raffaello Cimbro, Jinghe Huang, Mark Connors, Stephen D. Schmidt, Michael A. Dolan, Anthony A. Armstrong, Paolo Lusso
Summary: Research has identified key hydrophobic constraints at the apex of the HIV-1 envelope trimer that act as global stabilizers of the spike configuration. Mutations at the apex can increase sensitivity to certain neutralizing antibodies while decreasing sensitivity to others. Sera from chronically HIV-infected patients show enhanced potency in neutralizing open mutants compared to wild-type virus, indicating a significant target of antibodies on concealed epitopes.
Review
Biochemistry & Molecular Biology
Xia Li, Donghyun Park, Yunjie Chang, Abhijith Radhakrishnan, Hangjun Wu, Pei Wang, Jun Liu
Summary: The study introduces a model system based on PC12(+) cells and optimized imaging pipeline for high resolution imaging of organelles and molecular machines. The combination of various imaging techniques allows for quick generation of three-dimensional snapshots of organelles and molecular machines in mammalian cells, aiding in the dissection of specific cellular processes.
PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Tianshu Xiao, Jianming Lu, Jun Zhang, Rebecca I. Johnson, Lindsay G. A. McKay, Nadia Storm, Christy L. Lavine, Hanqin Peng, Yongfei Cai, Sophia Rits-Volloch, Shen Lu, Brian D. Quinlan, Michael Farzan, Michael S. Seaman, Anthony Griffiths, Bing Chen
Summary: This study introduces a trimeric ACE2 ectodomain variant engineered using a structure-based approach, which has a high binding affinity for the spike protein of SARS-CoV-2, preserved peptidase activity, and the ability to block angiotensin II receptor activation. The engineered ACE2 also shows potent inhibition of SARS-CoV-2 infection in cell culture, suggesting it may be a promising therapeutic agent for COVID-19.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Jun Zhang, Yongfei Cai, Tianshu Xiao, Jianming Lu, Hanqin Peng, Sarah M. Sterling, Richard M. Walsh, Sophia Rits-Volloch, Haisun Zhu, Alec N. Woosley, Wei Yang, Piotr Sliz, Bing Chen
Summary: Substitution of aspartic acid (D) with glycine (G) at position 614 in the spike protein of SARS-CoV-2 enhances viral spread. Cryo-electron microscopy structures reveal that the G614 strain has increased infectivity compared to the D614 strain. These findings provide insights for vaccine development and understanding viral entry mechanisms.
Article
Biotechnology & Applied Microbiology
Zhifang Zhang, Annie Yang, Shyambabu Chaurasiya, Anthony K. Park, Jianming Lu, Sang-In Kim, Susanne G. Warner, Yate-Ching Yuan, Zheng Liu, Haiyong Han, Daniel Von Hoff, Yuman Fong, Yanghee Woo
Summary: The study demonstrates that genetically modified oncolytic viruses can significantly upregulate PD-L1 expression in PDAC, and virus-delivered anti-PD-L1 antibodies can enhance anti-tumor immune killing in PDAC.
CANCER GENE THERAPY
(2022)
Article
Metallurgy & Metallurgical Engineering
Jianming Lu, David Dreisinger
Summary: The hydrometallurgical recovery of lead through methane sulfonic acid provides a green and potentially cost-effective lead production route. Electrowinning is the most feasible and economic way to produce lead metal in this method. The primary challenge is to produce smooth and dense lead deposits without the significant formation of PbO2 on an anode.
Article
Multidisciplinary Sciences
Yongfei Cai, Jun Zhang, Tianshu Xiao, Christy L. Lavine, Shaun Rawson, Hanqin Peng, Haisun Zhu, Krishna Anand, Pei Tong, Avneesh Gautam, Shen Lu, Sarah M. Sterling, Richard M. Walsh, Sophia Rits-Volloch, Jianming Lu, Duane R. Wesemann, Wei Yang, Michael S. Seaman, Bing Chen
Summary: The study found that the B.1.1.7 variant has increased receptor binding affinity, while the B.1.351 variant has developed resistance to some neutralizing antibodies by reshaping antigenic surfaces on the spike protein.
Review
Oncology
Shyambabu Chaurasiya, Sang-In Kim, Michael O'Leary, Anthony K. Park, Jianming Lu, Seonah Kang, Zhifang Zhang, Annie Yang, Yanghee Woo, Yuman Fong, Susanne G. Warner
Summary: Oncolytic viruses infect and kill cancer cells, while activating immune cells against tumors. Real-time tracking of viral replication and immune responses is crucial for enhancing treatment effects. Additional modalities to track virus-induced changes in tumor microenvironments are being explored.
MOLECULAR THERAPY-ONCOLYTICS
(2021)
Article
Engineering, Environmental
Wangbiao Guo, Lingchong Feng, Zhenyi Wang, Jiansheng Guo, Donghyun Park, Brittany L. Carroll, Xing Zhang, Jun Liu, Jun Cheng
Summary: This study uses a multidisciplinary approach to analyze the wild-type Chlorella pyrenoidosa and a nuclear-irradiated mutant. The mutant shows increased volume in subcellular organelles, overexpression of rubisco, and enlarged membrane width in the thylakoid, indicating enhanced carbon fixation and chlorophyll synthesis. This research provides detailed insights into how subcellular organelles collaborate to support macroscopic traits in microalgae.
CHEMICAL ENGINEERING JOURNAL
(2022)
Article
Metallurgy & Metallurgical Engineering
Jianming Lu, David Dreisinger, Rod McElroy, Colin Oloman, Bruce Downing, David Trueman
Summary: Cascadero Copper Corp. has developed a hydrometallurgical process to recover cesium from mineral samples in Argentina, optimizing the extraction and acid consumption.
Article
Multidisciplinary Sciences
Jun Zhang, Tianshu Xiao, Yongfei Cai, Christy L. Lavine, Hanqin Peng, Haisun Zhu, Krishna Anand, Pei Tong, Avneesh Gautam, Megan L. Mayer, Richard M. Walsh, Sophia Rits-Volloch, Duane R. Wesemann, Wei Yang, Michael S. Seaman, Jianming Lu, Bing Chen
Summary: The Delta variant of SARS-CoV-2 is more efficient at fusing membranes at low levels of cellular receptor ACE2, possibly contributing to its heightened transmissibility. Each variant shows different rearrangement of the antigenic surface of the S protein, but only the changes in the RBD make it a better target for therapeutic antibodies.
Article
Oncology
Sang-In Kim, Shyambabu Chaurasiya, Venkatesh Sivanandam, Seonah Kang, Anthony K. Park, Jianming Lu, Annie Yang, Zhifang Zhang, Isabella A. Bagdasarian, Yanghee Woo, Joshua T. Morgan, Zhirong Yin, Yuman Fong, Susanne G. Warner
Summary: Pancreatic cancer resistance to immunotherapies is partly due to deficits in tumor-infiltrating immune cells and stromal density. Combination therapies that modify stroma and recruit immune cells are needed. This study found that using Calcipotriol to modify the stroma can enhance oncolytic viroimmunotherapy. The results showed that Calcipotriol decreases fibrosis, increases immune cell infiltration, and reduces T cell exhaustion.
MOLECULAR THERAPY-ONCOLYTICS
(2022)
Article
Cell Biology
Jun Zhang, Yongfei Cai, Christy L. Lavine, Hanqin Peng, Haisun Zhu, Krishna Anand, Pei Tong, Avneesh Gautam, Megan L. Mayer, Sophia Rits-Volloch, Shaowei Wang, Piotr Sliz, Duane R. Wesemann, Wei Yang, Michael S. Seaman, Jianming Lu, Tianshu Xiao, Bing Chen
Summary: The Omicron variant of SARS-CoV-2 has a high number of mutations, which requires a higher level of ACE2 receptor for membrane fusion and shows increased resistance to neutralizing antibodies. This suggests that Omicron has acquired the ability to evade host immunity through excessive mutations.
Article
Oncology
Zhifang Zhang, Annie Yang, Shyambabu Chaurasiya, Anthony K. Park, Sang-In Kim, Jianming Lu, Tove Olafsen, Susanne G. Warner, Yuman Fong, Yanghee Woo
Summary: CF33-hNIS-antiPDL1 has anti-pancreatic adenocarcinoma activity and can infect, detect, and kill peritoneal tumors.
MOLECULAR THERAPY-ONCOLYTICS
(2022)
Article
Instruments & Instrumentation
Ling-Feng Lai, Deng -Maw Lu, Jian-Ming Lu
Summary: This study used the MD simulation method to investigate the thermomechanical properties of nanoscale hollow Pd nanoparticle pairs during additive manufacturing. The results showed that nanoscale Pd has much lower melting and coalescence temperatures than its macroscopic melting point, and solid-state sintering can occur at room temperature.
SENSORS AND MATERIALS
(2022)
Article
Virology
Hyung J. J. Kwon, Jun Zhang, Matina Kosikova, Weichun Tang, Uriel Ortega-Rodriguez, Hanqin Peng, Clement A. A. Meseda, Cyntia L. L. Pedro, Falko Schmeisser, Jianming Lu, Insung Kang, Bin Zhou, Charles T. T. Davis, David E. E. Wentworth, Wilbur H. H. Chen, Mallory C. C. Shriver, Robin S. S. Barnes, Marcela F. F. Pasetti, Jerry P. P. Weir, Bing Chen, Hang Xie
Summary: Researchers produced a set of mouse monoclonal antibodies targeting the ancestral SARS-CoV-2 receptor binding domain (RBD). Two antibodies, 17A7 and 17B10, showed high potency in inhibiting viral infection and protecting mice from lethal infections. Another antibody, 3A6, demonstrated strong neutralizing effects against Delta and Omicron BA.1 variants. These findings are valuable for antibody/vaccine design and for studying SARS-CoV-2 variants and immune responses.
JOURNAL OF MEDICAL VIROLOGY
(2023)