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
Multidisciplinary Sciences
Najla Arshad, Maudry Laurent-Rolle, Wesam S. Ahmed, Jack Chun-Chieh Hsu, Susan M. Mitchell, Joanna Pawlak, Debrup Sengupta, Kabir H. Biswas, Peter Cresswell
Summary: Two accessory proteins encoded by SARS-CoV-2, ORF3a and ORF7a, down-regulate MHC-I expression through distinct mechanisms, reducing surface MHC-I levels and enabling immune evasion by the virus.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Immunology
David Peterhoff, Stefanie Thalhauser, Jan M. Sobczak, Mona O. Mohsen, Christoph Voigt, Nicole Seifert, Patrick Neckermann, Alexandra Hauser, Song Ding, Quentin Sattentau, Martin F. Bachmann, Miriam Breunig, Ralf Wagner
Summary: Delivery of HIV-1 envelope (Env) trimer-based immunogens on nanoparticles can enhance immunogenicity and induce a potent, durable and broad neutralizing antibody response. Covalent conjugation of Env to silica nanoparticles (SiNPs) of different sizes shows high stability and improved uptake by dendritic cells. Multivalent Env displayed efficient activation of B cells even at low concentrations, and antibody responses to Env coupled with nanoparticles were stronger in mice compared to free protein.
Article
Biochemistry & Molecular Biology
Aathe Cangaree Arumugam, Fatima Ezzahra Agharbaoui, Ahmad Suhail Khazali, Rohana Yusof, Noorsaadah Abd Rahman, Abdullah Al Hadi Ahmad Fuaad
Summary: Dengue virus infection is a major global public health concern, without any specific antiviral treatment. This study aims to develop small peptide inhibitors targeting the virus entry process to block infection. One of the designed peptides, AC 001, shows the ability to reduce 40% of DV plaque formation. Computational analysis reveals the key residues involved in the binding of these peptides to the virus protein pocket.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Mario Cano-Munoz, Samuele Cesaro, Bertrand Morel, Julie Lucas, Christiane Moog, Francisco Conejero-Lara
Summary: The researchers increased the thermal stability of the gp41 single-chain proteins by mutating the core polar residues, but this also led to increased hydrophobicity. Furthermore, the mutations had a significant impact on the binding thermodynamics of CHR-derived peptides.
Article
Cell Biology
Angela R. Corrigan, Hongying Duan, Cheng Cheng, Christopher A. Gonelli, Li Ou, Kai Xu, Megan E. DeMouth, Hui Geng, Sandeep Narpala, Sarah O'Connell, Baoshan Zhang, Tongqing Zhou, Manjula Basappa, Jeffrey C. Boyington, Steven J. Chen, Sijy O'Dell, Amarendra Pegu, Tyler Stephens, Yaroslav Tsybovsky, Jelle van Schooten, John P. Todd, Shuishu Wang, Nicole A. Doria-Rose, Kathryn E. Foulds, Richard A. Koup, Adrian B. McDermott, Marit J. van Gils, Peter D. Kwong, John R. Mascola
Summary: The study found that priming with FP-conjugates, either alone or as part of a cocktail with SOSIP trimers, can reduce trimer-base responses and improve neutralization outcomes compared to priming with only trimers or a mixture of SOSIP trimer and FP conjugates.
Article
Multidisciplinary Sciences
Shang-Chuen Wu, Nourine A. Kamili, Marcelo Dias-Baruffi, Cassandra D. Josephson, Matthew F. Rathgeber, Melissa Y. Yeung, William J. Lane, Jianmei Wang, Hau-Ming Jan, Seth Rakoff-Nahoum, Richard D. Cummings, Sean R. Stowell, Connie M. Arthur
Summary: Adaptive immunity is regulated by tolerogenic mechanisms, but it faces challenges in combating microbes that mimic self-antigens. A study shows that the innate immune lectin Galectin-7 (Gal-7) can recognize various microbes that display blood group-like antigens, leading to their loss of viability without causing harm to host cells.
Article
Cell Biology
Zekun Mu, Kevin Wiehe, Kevin O. Saunders, Rory Henderson, Derek W. Cain, Robert Parks, Diana Martik, Katayoun Mansouri, Robert J. Edwards, Amanda Newman, Xiaozhi Lu, Shi-Mao Xia, Amanda Eaton, Mattia Bonsignori, David Montefiori, Qifeng Han, Sravani Venkatayogi, Tyler Evangelous, Yunfei Wang, Wes Rountree, Bette Korber, Kshitij Wagh, Ying Tam, Christopher Barbosa, S. Munir Alam, Wilton B. Williams, Ming Tian, Frederick W. Alt, Norbert Pardi, Drew Weissman, Barton F. Haynes
Summary: This study demonstrates that mRNA can encode antigenic Env trimers on ferritin nanoparticles, which can stimulate the expansion of broadly neutralizing antibody precursor B cells and induce neutralizing antibody activity against HIV-1. This finding has implications for the development of HIV-1 vaccines.
Article
Microbiology
Safia S. Aljedani, Tyler J. Liban, Karen Tran, Ganesh Phad, Suruchi Singh, Viktoriya Dubrovskaya, Pradeepa Pushparaj, Paola Martinez-Murillo, Justas Rodarte, Alex Mileant, Vidya Mangala Prasad, Rachel Kinzelman, Sijy O'Dell, John R. Mascola, Kelly K. Lee, Gunilla B. Karlsson Hedestam, Richard T. Wyatt, Marie Pancera
Summary: Understanding how antibodies target and neutralize specific regions of the HIV-1 envelope glycoprotein is crucial for vaccine development. Structural analysis revealed that vaccine-induced antibodies from different clonal lineages can penetrate the glycan shield to recognize a unique region within the V2 area, leading to potent neutralization of the autologous virus.
Review
Oncology
Saeid Taghiloo, Hossein Asgarian-Omran
Summary: Immune surveillance mechanisms are designed to eliminate AML development, but leukemic cells use immune evasion mechanisms to resist host immune responses, leading to tumor progression. While immune checkpoint inhibitors have achieved success in tumor-targeted therapy, their effectiveness in AML patients is less remarkable.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2021)
Article
Cell Biology
Jeong Hyun Lee, Catherine Nakao, Michael Appel, Amber Le, Elise Landais, Oleksandr Kalyuzhniy, Xiaozhen Hu, Alessia Liguori, Tina-Marie Mullen, Bettina Groschel, Robert K. Abbott, Devin Sok, William R. Schief, Shane Crotty
Summary: Inducing broadly neutralizing antibodies against HIV is challenging, but this study shows that using germline-targeting immunogens can lead to the accumulation of high-affinity antibodies with potent neutralization after a single immunization.
Review
Biochemistry & Molecular Biology
Nicole Hartwig Trier, Gunnar Houen, Giuseppe Murdaca
Summary: Autoimmunity is characterized by the presence of antibodies and/or T cells targeting self-components. It is often associated with infections, which may increase the risk of autoimmune diseases. Molecular mimicry, referring to cross-reactivity between foreign pathogens and self-antigens, can cause tissue damage and contribute to autoimmunity. This review aims to explore the nature of potential cross-reactive immune reactions between infectious non-self and self-tissue antigens associated with autoimmunity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Adam S. Dingens, Payal Pratap, Keara Malone, Sarah K. Hilton, Thomas Ketas, Christopher A. Cottrell, Julie Overbaugh, John P. Moore, P. J. Klasse, Andrew B. Ward, Jesse D. Bloom
Summary: The study utilized two methods to directly map the neutralizing and binding antibody specificities of polyclonal sera from rabbits immunized with HIV-1 antigens. Mutational antigenic profiling and electron microscopy polyclonal epitope mapping revealed differences in antibody specificities and provided important insights into polyclonal serum responses.
Review
Virology
Ariana Arduini, Frederique Laprise, Chen Liang
Summary: The COVID-19 pandemic has resulted in over 6.8 million deaths in the past three years, and the emergence of variants continues to strain global health. Understanding the viral mechanisms of SARS-CoV-2 and discovering new antiviral therapeutics are crucial to mitigating the impact of the virus.
Review
Cell Biology
Valeria Castelli, Andrea Lombardi, Emanuele Palomba, Giorgio Bozzi, Riccardo Ungaro, Laura Alagna, Davide Mangioni, Antonio Muscatello, Alessandra Bandera, Andrea Gori
Summary: ICIs play a crucial role in restoring the immune exhaustion state of T lymphocytes in cancer treatment; Their potential use and impact on safety and effectiveness in HIV-infected individuals are being explored; The administration of ICIs may influence opportunistic infections.
Article
Biochemistry & Molecular Biology
Acacia F. Dishman, Francis C. Peterson, Brian F. Volkman
Summary: XCL1 is a metamorphic protein that switches between two distinct native structures with different functions in the human immune system. Recent studies show that an engineered XCL1 variant called CC5 can regulate XCL1's structural equilibrium, resulting in an enrichment of the antimicrobial structure.
Article
Multidisciplinary Sciences
Acacia F. Dishman, Robert C. Tyler, Jamie C. Fox, Andrew B. Kleist, Kenneth E. Prehoda, M. Madan Babu, Francis C. Peterson, Brian F. Volkman
Summary: Through ancestral reconstruction and nuclear magnetic resonance, this study investigated the evolution of the metamorphic protein XCL1 and how it switches between two distinct folds. The evolution of XCL1 involved changes in dimer interface, structural constraints, and intramolecular protein contacts, leading to the development of its two different folds. These findings offer insights into how one sequence can evolve to encode multiple structures, with implications for protein design and engineering.
Article
Oncology
Deepak Parashar, Anjali Geethadevi, Donna McAllister, Johnathan Ebben, Francis C. Peterson, Davin R. Jensen, Erin Bishop, Sunila Pradeep, Brian F. Volkman, Michael B. Dwinell, Pradeep Chaluvally-Raghavan, Michael A. James
Summary: Recurrence of therapy-resistant tumors remains a major challenge in the field of solid tumor oncology, particularly in ovarian and pancreatic cancer. High expression of CLPTM1L in ovarian tumor cells is associated with poor prognosis, and inhibiting CLPTM1L can re-sensitize resistant ovarian cancer cells to platinum-based therapy. Additionally, CLPTM1L can confer intercellular resistance to chemotherapeutic killing in an ectodomain-dependent manner, which can be blocked by anti-CLPTM1L biologics.
NPJ PRECISION ONCOLOGY
(2021)
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)
Review
Virology
Qingbo Liu, Peng Zhang, Paolo Lusso
Summary: The entry of HIV-1 into host cells relies on interactions between the viral envelope spike and CD4 receptor, with complex conformational changes playing significant roles in the process. Understanding the quaternary nature of CD4-binding site in HIV-1 Env and its impact on interactions with CD4 receptor may offer insights for developing improved immunogens and antibodies targeting the CD4-binding site.
Article
Biochemistry & Molecular Biology
Eric M. Lewandowski, Kyle G. Kroeck, Lian M. C. Jacobs, Tyler G. Fenske, Robin N. Witt, Alyssa M. Hintz, Elizabeth R. Ramsden, Xiujun Zhang, Francis Peterson, Brian F. Volkman, Christopher T. Veldkamp, Yu Chen
Summary: This study presents the X-ray crystal structure of CCL19 and provides insights into its molecular features and potential receptor recognition sites. The computational analysis reveals differences in binding hotspots between CCL19 and CCL21.
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
Biochemistry & Molecular Biology
Acacia F. Dishman, Brian F. Volkman
Summary: Metamorphic proteins are single amino acid sequences that can reversibly convert between different conformations and have multiple functions. The challenges in this field include discovering more metamorphic proteins and designing new proteins that can switch conformations, which are important for disease treatment and protein-based therapies.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
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.
Article
Microbiology
Christian M. Berg, Michael R. Wedemeyer, Motiejus Melynis, Roman F. Schlimgen, Lasse Hansen, Jon F. Vabeno, Francis Peterson, Brian F. Volkman, Mette Rosenkilde, Hans F. Luettichau
Summary: This study investigates how the diversity of the UL146 gene in human cytomegalovirus (HCMV) affects its signaling and structural properties. The researchers find that certain genotypes exhibit similar functions despite lacking key structural domains, and many of the genotypes contain novel structural elements critical for protein folding. The findings highlight the host-adaptation of HCMV and propose novel structural interactions with implications for the virus-host interplay.
Article
Biochemistry & Molecular Biology
Holly N. Haver, Michael Wedemeyer, Erin Butcher, Francis C. Peterson, Brian F. Volkman, K. Matthew Scaglione
Summary: Protein aggregation is a key feature of polyglutamine diseases. This study focuses on understanding how serine-rich chaperone protein 1 (SRCP1) suppresses polyglutamine aggregation and its potential therapeutic implications. Through protein modeling and experimental validation, the study reveals the structural basis of SRCP1's inhibitory effect on protein aggregation and its mechanism of action. The findings also demonstrate that SRCP1 can inhibit aggregation of different polyglutamine-expanded proteins.
ACS CHEMICAL BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Acacia F. Dishman, Brian F. Volkman
Summary: Metamorphic proteins can switch between different stable structures with different functions, and they are not rare or transient exceptions to the 'one sequence, one fold' paradigm. The NusG family and the chemokine XCL1 are examples of metamorphic proteins that have preserved and optimized their folding over evolutionary time. Analysis of current protein families and resurrected protein ancestors shows that a large portion of sequence space is compatible with metamorphic folding. As a category that enhances biological fitness, metamorphic proteins are likely to utilize fold switching for important biological functions and may be more common than previously thought.
TRENDS IN BIOCHEMICAL SCIENCES
(2023)
Article
Biochemical Research Methods
Angela L. Zhou, Davin R. Jensen, Francis C. Peterson, Monica A. Thomas, Roman R. Schlimgen, Michael B. Dwinell, Brian C. Smith, Brian F. Volkman
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)