Article
Virology
Ruohan Zhu, Xiaohong Sang, Jiao Zhou, Qian Meng, Lina S. M. Huang, Yan Xu, Jing An, Ziwei Huang
Summary: Human immunodeficiency virus-1 (HIV-1) uses the third variable loop (V3 loop) of its envelope glycoprotein gp120 to recognize the coreceptor CXCR4 on host cells during viral entry. Synthetic peptides containing the full-length V3 loop were used to investigate the molecular recognition mechanism between HIV-1 gp120 V3 loop and CXCR4. The results show that the cyclic L- and D-V3 loop peptides have comparable binding to CXCR4 and selectively interact with it, indicating the flexibility of the HIV-1 gp120 V3 loop-CXCR4 interface for ligands with different chiralities.
Article
Virology
Saumya Anang, Shijian Zhang, Christopher Fritschi, Ta-Jung Chiu, Derek Yang, Amos B. Smith, Navid Madani, Joseph Sodroski
Summary: CD4-mimetic compounds (CD4mcs) can inhibit the entry of HIV-1 into host cells. Changes distant from the binding pocket can influence the susceptibility of natural HIV-1 strains to the antiviral effects of multiple CD4mcs.
JOURNAL OF VIROLOGY
(2023)
Article
Immunology
Yueyang Yu, Yi Feng, Zehua Zhou, Kang Li, Xiaoyan Hu, Lingjie Liao, Hui Xing, Yimig Shao
Summary: HIV-1 infection is mediated by the viral envelope binding to CD4 receptor and coreceptors CCR5 and CXCR4. Switching between these coreceptors is associated with increased pathogenesis and disease progression. Our study identified that the V3 loop and C4 region of the HIV-1 envelope are determinants for coreceptor switching. The mechanisms include enabling envelope binding to the new coreceptor and compensating for fitness loss caused by V3 loop mutations. This study has implications for HIV-1 surveillance and the selection of antiviral therapy.
EMERGING MICROBES & INFECTIONS
(2023)
Article
Biophysics
Elizabeth Kruse, Tamer Abdalrahman, Philippe Selhorst, Thomas Franz
Summary: This study aimed to develop a mathematical model to explore the interactions between HIV particles and host cells, and investigate the effects of mechanical and morphological parameters on the engulfment process. The results showed that low invagination force and high ligand-receptor energy are associated with high virion entry ability. Changes during virion maturation and localized membrane features of immune cells also influence the engulfment energy. The developed mathematical model offers potential for improving the prevention and treatment of viral infections.
BIOMECHANICS AND MODELING IN MECHANOBIOLOGY
(2023)
Article
Microbiology
Chuyu Zhang, Yun Lan, Linghua Li, Ruiying He, Yu Meng, Jian Li, Weilie Chen
Summary: This study investigated the factors associated with different HIV-1 tropisms in low-level viral load HIV-1 infections in China. The majority of infections in Guangdong receiving highly active antiretroviral therapy for more than 6 months were R5-tropic, and the baseline immune level was lower in X4-tropic infections. Furthermore, certain amino acid variations were associated with X4-tropic HIV-1.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Chemistry, Medicinal
Ruohan Zhu, Qian Meng, Huijun Zhang, Ge Zhang, Lina S. M. Huang, Yan Xu, Robert T. Schooley, Jing An, Ziwei Huang
Summary: Through investigating the molecular recognition mechanism between HIV-1 gp120 V3 loop and coreceptor CXCR4, it was found that the ligand-receptor recognition between CXCR4 and V3 loop fragments exhibits flexible stereospecificity. This study is important for understanding the viral entry mechanism and how the virus evades immune detection with V3 loop mutations while maintaining effective recognition of the host cell's coreceptor.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Meng-Ting Liu, Jian-Xin Shen, Xin-Wei Li, Li Yang, Yi Li, Peng Sang, Li-Quan Yang
Summary: In this study, structural models of gp120 from two different HIV-1 strains were constructed and molecular dynamics simulations were carried out to investigate the differences in their neutralization phenotypes. The results showed that the gp120 from the CD4-independent strain R2 had higher structural flexibility and conformational diversity, leading to a more open conformation compared to the CD4-dependent strain JR-FL. This difference in conformational states explained the CD4-dependent and -independent phenotypes of the two strains. The study provides important insights into the molecular mechanisms of HIV-1 gp120 and contributes to the understanding of HIV-1 immune evasion.
Article
Biochemistry & Molecular Biology
Juan S. Rey, Wen Li, Alexander J. Bryer, Hagan Beatson, Christian Lantz, Alan N. Engelman, Juan R. Perilla
Summary: Transmission electron microscopy is widely used in biomedical imaging for discerning ultrastructure morphology at the nanometer scale, with a particular focus on visualizing virus particles. A newly developed RCNN backbone shows promising results in identifying and classifying HIV-1 virions at different stages of maturation and morphogenesis, outperforming common RCNN backbones.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Gastroenterology & Hepatology
Maika S. Deffieu, Camille M. H. Clement, Cristina M. Dorobantu, Emma Partiot, Yonis Bare, Orestis Faklaris, Benjamin Riviere, Nilda Vanesa Ayala-Nunez, Thomas F. Baumert, Philippe Ronde, Yves Mely, Vincent Lucansky, Raphael Gaudin
Summary: This study provides robust evidence that HCV particles interact with OCLN away from TJs and sheds mechanistic insights regarding the manipulation of transmembrane receptor localization by extracellular virus particles.
Article
Microbiology
James P. Cwick, Jonathan E. Owen, Irina Kochetkova, Kyle S. Hain, Nick Van Horssen, Matthew P. Taylor
Summary: Most viruses utilize superinfection exclusion (SIE) to conserve resources and control population dynamics. This study provides new insights into how alphaherpesviruses limit sequential infection through the undercharacterized gD-independent SIE, which differs between PRV and HSV-1.
MICROBIOLOGY SPECTRUM
(2022)
Article
Virology
Philippe Gatault, Iris K. A. Jones, Christine Meyer, Craig Kreklywich, Timothy Alexander, Patricia P. Smith, Michael Denton, Josh Powell, Susan L. Orloff, Daniel N. Streblow
Summary: Herpesviruses encode multiple glycoproteins for various stages of viral processes; HCMV UL116 forms a stable complex with glyocoprotein H; RCMV R116 is involved in viral infectivity.
Article
Biochemistry & Molecular Biology
Jimin Yoon, Emmanuel E. Nekongo, Jessica E. Patrick, Tiffani Hui, Angela M. Phillips, Anna I. Ponomarenko, Samuel J. Hendel, Rebecca M. Sebastian, Yu Meng Zhang, Vincent L. Butty, C. Brandon Ogbunugafor, Yu-Shan Lin, Matthew D. Shoulders
Summary: This study investigates the impact of proteostasis networks on the sequence space accessible to HIV-1 envelope protein. The upregulation of the unfolded protein response is found to globally reduce the mutational tolerance of the envelope protein, while specific regions targeted by broadly neutralizing antibodies exhibit enhanced mutational tolerance. These findings highlight the importance of proteostasis networks in shaping the mutational tolerance of client proteins and have implications for HIV adaptation.
Review
Biochemistry & Molecular Biology
Qiangmin Zhang, Peter A. Friedman
Summary: SARS-CoV-2 utilizes the respiratory epithelium and interacts with cell junction-associated proteins to disrupt the inter-epithelial barrier, causing multiorgan injury. ACE2 and NRP1 receptors with wide tissue distribution in lung, intestine, and kidney serve as major entry sites for the virus. PDZ interaction enhances viral invasion by supporting viral receptor membrane residence, suggesting a potential therapeutic strategy against COVID-19.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Jerry Joe E. K. Harrison, Dario Oliveira Passos, Jessica F. Bruhn, Joseph D. Bauman, Lynda Tuberty, Jeffrey J. DeStefano, Francesc Xavier Ruiz, Dmitry Lyumkis, Eddy Arnold
Summary: In this study, the cryo-electron microscopy structure of stable HIV-1 Pol was determined, revealing that RT in the Pol has a similar arrangement to the mature RT heterodimer. The dimerization of RT may activate proteolytic processing by bringing two PR monomers together. This finding suggests that HIV-1 leverages the dimerization interfaces in Pol to regulate assembly and maturation of polyprotein precursors.
Article
Biochemical Research Methods
Rachel M. Miller, Rachel A. Knoener, Bayleigh E. Benner, Brian L. Frey, Mark Scalf, Michael R. Shortreed, Nathan M. Sherer, Lloyd M. Smith
Summary: Through proteomic analysis of HIV-1 virions, novel post-translational modifications of highly conserved residues within the viral matrix and capsid proteins were discovered, forming dehydroamino acids dehydroalanine and dehydrobutyrine. These rare and understudied dehydroamino acids may play an important role in viral particle maturation and provide valuable insights into HIV infectivity mechanisms.
JOURNAL OF PROTEOME RESEARCH
(2022)
Article
Plant Sciences
Chang-Kwon Kim, Dongdong Wang, Heidi R. Bokesch, Richard W. Fuller, Emily Smith, Curtis J. Henrich, David E. Durrant, Deborah K. Morrison, Carole A. Bewley, Kirk R. Gustafson
JOURNAL OF NATURAL PRODUCTS
(2020)
Article
Microbiology
T. Parks Remcho, Sravanthi D. Guggilapu, Phillip Cruz, Glenn A. Nardone, Gavin Heffernan, Robert D. O'Connor, Carole A. Bewley, Thomas E. Wellems, Kristin D. Lane
Summary: WR99210 selectively targets Plasmodium parasites, with compound 1 effective against Plasmodium falciparum at low concentrations, while compound 2 is ineffective. Structural evaluations revealed compound 1 as WR99210 and compound 2 as a dihydrotriazine regioisomer, with different binding capabilities to the parasite's enzyme.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Chemistry, Organic
Jiadong Sun, Gengxiang Zhao, Robert D. OConnor, Jack R. Davison, Carole A. Bewley
Summary: Six novel pyranonaphthoquinones, named vertirhodins A-F, were discovered from a soil-derived Streptomyces sp. B15-008. Their chemical structures and absolute configurations were determined using nuclear magnetic resonance and comparison of experimental and theoretical electronic circular dichroism spectra. A plausible biosynthetic gene cluster for these compounds was identified through whole genome sequencing, providing insights into their unique structural features.
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.
Article
Cell Biology
Arvin Tejnarine Persaud, Stephen Andrew Bennett, Laxshaginee Thaya, Jonathan Burnie, Christina Guzzo
Summary: This study identifies a previously undescribed reservoir of preformed chemokine CCL5 in circulating human monocytes, allowing for immediate secretion of immune mediators upon activation, bypassing the time lag associated with de novo synthesis of cytokines. This finding implicates endosomal compartments in the intracellular storage and trafficking of CCL5 in monocytes.
JOURNAL OF LEUKOCYTE BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Gengxiang Zhao, Dalibor Kosek, Hong-Bing Liu, Shannon Ohlemacher, Brittney Blackburne, Anastasia Nikolskaya, Kira S. Makarova, Jiadong Sun, Clifton E. Barry, Eugene Koonin, Fred Dyda, Carole A. Bewley
Summary: Chryseoviridin, a newly discovered multicore RiPP, contains four consecutive five- or six-residue macrocycles ending with a microviridin-like core. The crystal structure reveals a significant conformational change in the B-domain of the ATP-grasp ligase CdnC upon substrate binding, providing insights into omega-ester bond formation in RiPP biosynthesis. Experimental validation confirms a model where macrocyclization occurs in the N- to C-terminal direction for core peptides containing multiple Thr/Ser-to-Asp macrocycles.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Hong-Bing Liu, Jack R. Davison, Rahim Rajwani, Gengxiang Zhao, Shannon I. Ohlemacher, Robert D. O'Connor, Carole A. Bewley
Summary: Pyrazines are a significant group of natural products with various biological effects, isolated from Lentzea sp. GA3-008 in this study. The structures of lentzeacins and known analogues were determined using NMR spectroscopy and HR-ESI-MS, shedding light on the biosynthesis possibilities in this strain. The presence of 40 biosynthetic gene clusters in Lentzea sp. indicates its potential for producing bioactive compounds.
Article
Virology
Arvin T. Persaud, Jonathan Burnie, Laxshaginee Thaya, Liann DSouza, Steven Martin, Christina Guzzo
Summary: This study demonstrates the effectiveness of ultraviolet light-emitting diodes in inactivating viruses and bacteria, suggesting that UV-LED could be a practical tool for sanitizing public spaces.
Article
Microbiology
Rahim Rajwani, Shannon Ohlemacher, Gengxiang Zhao, Hong-Bing Liu, Carole A. Bewley
Summary: Genome mining is crucial for discovering new natural products, and long-read sequencing methods are necessary for obtaining contiguous DNA assemblies for analyzing biosynthetic gene clusters. The Flongle platform by Oxford Nanopore Technologies provides a low-cost option for such sequencing needs, allowing for multiplexing and efficient analysis of BGCs even at low sequencing depth.
Article
Biochemistry & Molecular Biology
Jiadong Sun, Gengxiang Zhao, Tatsiana Bylund, Myungjin Lee, Srikar Adibhatla, Peter D. Kwong, Gwo-Yu Chuang, Reda Rawi, Carole A. Bewley
Summary: Lectins, such as the therapeutic lectin griffithsin (GRFT), have the potential to bind to carbohydrates and glycan shields, making them promising for therapeutic and diagnostic applications. By studying the structure and activity of GRFT, researchers have identified a critical core structure that is important for antiviral activity and binding to high mannose glycans. This discovery may help in designing carbohydrate receptors and improving the affinity and stability of known lectins.
ACS CHEMICAL BIOLOGY
(2022)
Article
Biology
Kira S. Makarova, Brittney Blackburne, Yuri Wolf, Anastasia Nikolskaya, Svetlana Karamycheva, Marlene Espinoza, Clifton E. Barry, Carole A. Bewley, Eugene Koonin
Summary: This study comprehensively analyzed BGCs encoding graspetides and reported several novel graspetide groups and associated proteins involved in their biosynthesis and expression. The results revealed previously unsuspected diversity in graspetide sequences and expanded the known diversity of RiPPs. The findings of this study are important for advancing approaches to identify RiPPs.
Article
Virology
Jonathan Burnie, Arvin Tejnarine Persaud, Laxshaginee Thaya, Qingbo Liu, Huiyi Miao, Stephen Grabinsky, Vanessa Norouzi, Paolo Lusso, Vera A. Tang, Christina Guzzo
Summary: PSGL-1 plays diverse roles in HIV-1 infection due to its functional activity on virion surfaces and broad incorporation among a wide range of viral isolates.
Review
Chemistry, Multidisciplinary
Carole A. Bewley, Gary A. Sulikowski, Zhongyue J. Yang, Giuseppe Bifulco, Hyo-Moon Cho, Christopher R. Fullenkamp
Summary: Natural products, produced by enzymatic assembly lines, have played a crucial role in the discovery of antibiotics, antineoplastics, and therapeutics. They have unique three-dimensional shapes and stereochemistry, which determine their diverse functions and biological activities. With advancements in methods and tools, research on atropisomerism in natural products and related scaffolds is progressing.
ACCOUNTS OF CHEMICAL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Edurne Rujas, Hong Cui, Jonathan Burnie, Clare Burn Aschner, Tiantian Zhao, Sara Insausti, Krithika Muthuraman, Anthony Semesi, Jasper Ophel, Jose L. Nieva, Michael S. Seaman, Christina Guzzo, Bebhinn Treanor, Jean-Philippe Julien
Summary: In this study, HIV-1 bNAbs were engineered by directly fusing their Fab fragments to the human apoferritin light chain, resulting in a multispecific and avid molecule. The molecule exhibited high neutralization potency against a broad panel of HIV-1 pseudoviruses and demonstrated IgG-like bioavailability in vivo through Fc receptor modulation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Virology
Jonathan Burnie, Vera A. Tang, Joshua A. Welsh, Arvin T. Persaud, Laxshaginee Thaya, Jennifer C. Jones, Christina Guzzo