Article
Immunology
Sarah Vollmers, Annabelle Lobermeyer, Annika Niehrs, Pia Fittje, Daniela Indenbirken, Jacqueline Nakel, Sanamjeet Virdi, Sebastien Brias, Timo Trenkner, Gabriel Sauer, Sven Peine, Georg M. N. Behrens, Clara Lehmann, Anja Meurer, Ramona Pauli, Nils Postel, Julia Roider, Stefan Scholten, Christoph D. Spinner, Christoph Stephan, Eva Wolf, Christoph Wyen, Laura Richert, Paul J. Norman, Juergen Sauter, Alexander H. Schmidt, Angelique Hoelzemer, Marcus Altfeld, Christian Koerner
Summary: NK cells play a crucial role in antiviral immunity, and KIR receptors regulate NK cell activity and recognition of target cells. HLA-C serves as the primary ligand for KIRs, and interactions between HLA-C and inhibitory KIR2DL receptors may contribute to HIV-1 immune evasion. This study found significant changes in the NK cell receptor repertoire in HIV-1-infected individuals and suggested that KIR/HLA-C genotypes may impact HIV-1 immune escape.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Chemistry, Medicinal
Xinxin Zhong, Ronghua Luo, Guoyi Yan, Kai Ran, Huifang Shan, Jie Yang, Yuanyuan Liu, Su Yu, Chunlan Pu, Yongtang Zheng, Rui Li
Summary: Through the optimization of the Vif antagonist ring C, compound 6m was discovered to exhibit stronger antiviral activity compared to 2, as well as effectively suppress the replication of various drug-resistant HIV strains, making it a more potent candidate for treating AIDS.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Infectious Diseases
Basma Abdi, Sidonie Lambert-Niclot, Marc Wirden, Aude Jary, Elisa Teyssou, Sophie Sayon, Romain Palich, Roland Tubiana, Anne Simon, Marc-Antoine Valantin, Christine Katlama, Laurence Morand-Joubert, Vincent Calvez, Anne-Genevieve Marcelin, Cathia Soulie
Summary: The study reveals an association between virological and clinical factors and APOBEC3 editing activity, with G-to-A mutations and stop codons in the reverse transcriptase gene as markers of HIV-1 diversity among virologically suppressed patients. A higher prevalence of hypermutated sequences was found in the APOBEC+ group, while the total cell-associated HIV-1 DNA level was lower in this group compared to the APOBEC- group.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Virology
Susana Bandarra, Eri Miyagi, Ana Clara Ribeiro, Joao Goncalves, Klaus Strebel, Isabel Barahona
Summary: A3G is a strong restriction factor for both HIV-1 and HIV-2, while A3C has no restriction potential. A3B exhibits potent antiviral activity against HIV-2 but not HIV-1, indicating different mechanisms for both viruses in antagonizing A3B. HIV-2 Vif targets A3B by reducing its levels and inhibiting its packaging into virions, while HIV-1 Vif does not antagonize A3B.
JOURNAL OF VIROLOGY
(2021)
Article
Infectious Diseases
Monray Edward Williams
Summary: This study explored the diversity of Viral Infectivity Factor (Vif) sequences in HIV-1C prevalent regions, focusing on South Africa. The findings revealed distinct genetic variations between different geographic groups, and specific amino acid substitutions in Vif were associated with these groups. Molecular modeling and docking analyses identified key residues responsible for the interaction between Vif and APOBEC3G.
EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES
(2023)
Article
Medicine, Research & Experimental
Anju Bansal, Mika N. Gehre, Kai Qin, Sarah Sterrett, Ayub Ali, Ying Dang, Sojan Abraham, Margaret C. Costanzo, Leon A. Venegas, Jianming Tang, N. Manjunath, Mark A. Brockman, Otto O. Yang, June Kan-Mitchell, Paul A. Goepfert
Summary: The study reveals that HLA-E-restricted CD8(+) T cell responses play a crucial role in determining the immunodominance of CD8(+) T cell responses in HIV infection, shedding light on the immune mechanisms involved in HIV pathogenesis.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Immunology
Hongbing Yang, Margarida Rei, Simon Brackenridge, Elena Brenna, Hong Sun, Shaheed Abdulhaqq, Michael K. P. Liu, Weiwei Ma, Prathiba Kurupati, Xiaoning Xu, Vincenzo Cerundolo, Edward Jenkins, Simon J. Davis, Jonah B. Sacha, Klaus Frueh, Louis J. Picker, Persephone Borrow, Geraldine M. Gillespie, Andrew J. McMichael
Summary: HLA-E plays a crucial role in immune response, and vaccine-induced HLA-E-restricted HIV-1-specific T cells have the potential to suppress HIV-1 replication.
SCIENCE IMMUNOLOGY
(2021)
Article
Immunology
Yu Wang, Gui Qian, Lingyan Zhu, Zhuo Zhao, Yinan Liu, Wendong Han, Xiaokai Zhang, Yihua Zhang, Tingrong Xiong, Hao Zeng, Xianghui Yu, Xiaofang Yu, Xiaoyan Zhang, Jianqing Xu, Quanming Zou, Dapeng Yan
Summary: HIV-1 infection inhibits the production of type I interferon by using Vif to evade host immune response, providing insights into a novel mechanism for HIV-1 to escape antiviral immunity by interfering with STING posttranslational modification. These findings could offer a foundation for developing new therapeutic strategies for treating HIV-1 infection.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Boye Li, Xiaoxiao Dong, Wenmei Zhang, Tian Chen, Boyang Yu, Wenyue Zhao, Yishu Yang, Xiaoli Wang, Qin Hu, Xiayan Wang
Summary: BST-2 is a host restriction factor that suppresses the release of enveloped viruses by tethering viral particles to the cell surface. Inhibiting the interaction between Vpu and BST-2 could provide a promising strategy for anti-HIV therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Microbiology
Daniel J. Salamango, Reuben S. Harris
Summary: Accessory proteins like Vif play a crucial role in distinguishing primate immunodeficiency viruses such as HIV-1, by not only antagonizing APOBEC3 enzymes but also triggering cell cycle arrest through the degradation of PPP2R5 proteins. These functions of Vif have opened up new avenues for accessory protein research and potential opportunities for drug development.
FRONTIERS IN MICROBIOLOGY
(2021)
Editorial Material
Microbiology
Robert Z. Zhang, Melissa Kane
Summary: HIV-1 both inhibits and activates the NF-kappa B pathway, which is important for the viral life cycle. The viral protein U has contrasting effects on beta-TrCP1 and beta-TrCP2, leading to dysregulation of the NF-kappa B pathways. These findings enhance our understanding of how the NF-kappa B pathway functions during viral infection.
Article
Medicine, Research & Experimental
Gabriel Duette, Bonnie Hiener, Hannah Morgan, Fernando G. Mazur, Vennila Mathivanan, Bethany A. Horsburgh, Katie Fisher, Orion Tong, Eunok Lee, Haelee Ahn, Ansari Shaik, Remi Fromentin, Rebecca Hoh, Charline Bacchus-Souffan, Najla Nasr, Anthony L. Cunningham, Peter W. Hunt, Nicolas Chomont, Stuart G. Turville, Steven G. Deeks, Anthony D. Kelleher, Timothy E. Schlub, Sarah Palmer
Summary: Through studying CD4(+) T cells of HIV-1 patients, the importance of effector memory T cells in the persistence of HIV-1 has been identified, and Nef has been suggested as a potential therapeutic target.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Microbiology
Pia Fittje, Angelique Hoelzemer, Wilfredo F. Garcia-Beltran, Sarah Vollmers, Annika Niehrs, Kerri Hagemann, Gloria Martrus, Christian Korner, Frank Kirchhoff, Daniel Sauter, Marcus Altfeld
Summary: This study identified the binding of KIR2DL5 with the poliovirus receptor (PVR, CD155) rather than HLA class I or class II molecules. It demonstrated that HIV-1 decreases CD155 expression on infected CD4(+) T cells via a Nef-dependent mechanism, leading to enhanced anti-viral activity of KIR2DL5(+) NK cells against HIV-1-infected cells.
Article
Microbiology
Suzanne Pickering, Jonathan Sumner, Claire Kerridge, Marianne Perera, Stuart Neil
Summary: The HIV-1 Vpu protein inhibits NF-κB signaling by binding and inhibiting β-TrCP, and it simultaneously exploits the different paralogues of β-TrCP to degrade its cellular targets, resulting in potent inhibition of both the canonical and non-canonical NF-κB pathways.
Article
Biochemistry & Molecular Biology
Chiara Stefani, Antonella Sangalli, Elena Locatelli, Tania Federico, Giovanni Malerba, Maria Grazia Romanelli, Gustavo Adolfo Arganaraz, Bosco Christiano Maciel Da Silva, Alberto Jose Duarte Da Silva, Jorge Casseb, Enrique Roberto Arganaraz, Alessandra Ruggiero, Donato Zipeto
Summary: This study found a correlation between unstable HLA-C variants and rapid progression to AIDS, providing new insights into the impact of host genetic factors on AIDS progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Immunology
Jung-Hyun Lee, Lennart Koepke, Frank Kirchhoff, Konstantin M. J. Sparrer
Summary: The innate immune system relies on interferons to combat viral infections. However, successful viruses like SARS-CoV-2 have evolved strategies to evade the interferon system and establish an anti-viral state.
MEDICAL MICROBIOLOGY AND IMMUNOLOGY
(2023)
Article
Virology
Lukas Wettstein, Patrick Immenschuh, Tatjana Weil, Carina Conzelmann, Yasser Almeida-Hernandez, Markus Hoffmann, Amy Kempf, Inga Nehlmeier, Rishikesh Lotke, Moritz Petersen, Steffen Stenger, Frank Kirchhoff, Daniel Sauter, Stefan Poehlmann, Elsa Sanchez-Garcia, Jan Muench
Summary: Host cell protease TMPRSS2 plays a critical role in the tropism and pathogenesis of SARS-CoV-2, and antithrombin (AT) is identified as a broad-spectrum inhibitor of coronavirus infection by blocking TMPRSS2 activity. AT can inhibit the entry of various coronaviruses, including SARS-CoV, MERS-CoV, hCoV-229E, SARS-CoV-2, and the Omicron variant, as well as suppress lung cell infection with genuine SARS-CoV-2. Activation of AT by anticoagulants enhances its activity against TMPRSS2 and SARS-CoV-2, suggesting the potential of repurposing AT for COVID-19 treatment.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Chemistry, Medicinal
Cheyenne Chaplain, Christopher J. Fritschi, Saumya Anang, Zhen Gong, Jonathan Richard, Catherine Bourassa, Shuaiyi Liang, Mohammadjavad Mohammadi, Jun Park, Andres Finzi, Navid Madani, Joseph G. Sodroski, Cameron F. Abrams, Wayne A. Hendrickson, Amos B. Smith III
Summary: CD4-mimetic compounds have the potential to block the entry of HIV-1 into host cells. By modifying the compound structure, it is possible to enhance its antiviral activity and sensitivity, opening up the possibility for the development of more potent drugs.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
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
Cell Biology
Irfan Ullah, Guillaume Beaudoin-Bussieres, Kelly Symmes, Marc Cloutier, Eric Ducas, Alexandra Tauzin, Annemarie Laumaea, Michael W. Grunst, Katrina Dionne, Jonathan Richard, Philippe Begin, Walther Mothes, Priti Kumar, Renee Bazin, Andres Finzi, Pradeep D. Uchil
Summary: COVID-19 convalescent plasmas (CCPs) for plasma therapy are selected based on neutralizing titers and anti-Spike immunoglobulin levels. CCPs with moderate to high Fc-effector activity, despite low neutralizing ability, delay mortality and/or improve survival in SARS-CoV-2-challenged mice. The Fc-effector functions of CCPs contribute to immunity against variant strains.
CELL REPORTS MEDICINE
(2023)
Letter
Critical Care Medicine
Daniel Gagiannis, Carsten Hackenbroch, Wilhelm Bloch, Fabian Zech, Frank Kirchhoff, Sonja Djudjaj, Saskia von Stillfried, Roman Buelow, Peter Boor, Konrad Steinestel
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Lia-Raluca Olari, Richard Bauer, Marta Gil Miro, Verena Vogel, Laura Cortez Rayas, Ruediger Gross, Andrea Gilg, Raphael Klevesath, Armando A. Rodriguez Alfonso, Kuebra Kaygisiz, Ulrich Rupp, Pradeep Pant, Joel Mieres-Perez, Lena Steppe, Ramona Schaeffer, Lena Rauch-Wirth, Carina Conzelmann, Janis A. Mueller, Fabian Zech, Fabian Gerbl, Jana Bleher, Nico Preising, Ludger Staendker, Sebastian Wiese, Dietmar R. Thal, Christian Haupt, Hendrik R. A. Jonker, Manfred Wagner, Elsa Sanchez-Garcia, Tanja Weil, Steffen Stenger, Marcus Faendrich, Jens von Einem, Clarissa Read, Paul Walther, Frank Kirchhoff, Barbara Spellerberg, Jan Muench
Summary: Antimicrobial peptides (AMPs) are important components of innate immune defense and their antibacterial activity is often dependent on the formation of amyloid-like fibrils. In this study, a spleen-derived peptide library was used to identify novel fibril forming AMPs, leading to the discovery of HBA(111-142), a fragment of alpha-hemoglobin. HBA(111-142) fibrils exhibited membranolytic activity against bacteria and selectively inhibited certain viruses, suggesting its potential role in innate antimicrobial immune responses.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Virology
Moritz Petersen, Rishikesh Lotke, Kristina Hopfensperger, Sabina Victoria, Isabell Haussmann, Timo Burster, Hanna-Mari Baldauf, Daniel Sauter
Summary: Serpins are a superfamily of proteins that irreversibly inhibit serine proteases and regulate physiological processes. Serpin B8 can inhibit the proteolytic activation of HIV-1 Env by binding to furin, but only when it is relocalized to the secretory pathway. This study provides insights into the biology of Serpins and demonstrates the potential of protein engineering for antiviral treatment.
JOURNAL OF VIROLOGY
(2023)
Article
Pediatrics
Alina Seidel, Eva-Maria Jacobsen, Dorit Fabricius, Magdalena Class, Maria Zernickel, Carmen Blum, Carina Conzelmann, Tatjana Weil, Ruediger Gross, Sebastian F. N. Bode, Hanna Renk, Roland Elling, Maximillian Stich, Frank Kirchhoff, Klaus-Michael Debatin, Jan Muench, Ales Janda
Summary: This study investigated the serum neutralization capacity and T cell memory responses of 36 seropositive adults and 34 children approximately one year after infection with the ancestral Wuhan strain of SARS-CoV-2. The results showed that a high percentage of both adults and children retained neutralizing activity against the SARS-CoV-2 Wuhan strain, although the neutralization effect against the Omicron BA.1 variant was lower. Additionally, specific T cell memory responses against the Wuhan strain and the BA.1 variant were detected in both adults and children.
FRONTIERS IN PEDIATRICS
(2023)
Article
Multidisciplinary Sciences
Qinya Xie, Caterina Prelli Bozzo, Laura Eiben, Sabrina Noettger, Dorota Kmiec, Rayhane Nchioua, Daniela Niemeyer, Meta Volcic, Jung-Hyu Lee, Fabian Zech, Konstantin M. J. Sparrer, Christian Drosten, Frank Kirchhoff
Summary: Opposing effects of IFITMs on SARS-CoV-2 infection have been reported, but their role in other hCoVs remains unclear. This study finds that IFITM2 and/or IFITM3 are critical for efficient replication of SARS-CoV-1, SARS-CoV-2, and hCoV-OC43, but have little effect on MERS, NL63, and 229E-hCoVs. Overexpression of IFITMs inhibits all hCoVs except OC43, and impairs cell surface expression of ACE2, the entry receptor for SARS-CoVs and hCoV-NL63. These results explain the inhibitory effects of artificial IFITM overexpression on ACE2-tropic SARS-CoVs and demonstrate the hijacking of IFITMs by three hCoVs for efficient infection in human cells.
Article
Biology
Rayhane Nchioua, Annika Schundner, Susanne Klute, Lennart Koepke, Maximilian Hirschenberger, Sabrina Noettger, Giorgio Fois, Fabian Zech, Alexander Graf, Stefan Krebs, Peter Braubach, Helmut Blum, Steffen Stenger, Dorota Kmiec, Manfred Frick, Frank Kirchhoff, Konstantin M. J. Sparrer
Summary: The IFN system is a powerful antiviral defense mechanism. Effective IFN responses protect against severe COVID-19 and exogenous IFNs inhibit SARS-CoV-2 in vitro. However, emerging SARS-CoV-2 variants of concern (VOCs) may have evolved reduced IFN sensitivity. This study found that the Omicron variant was least restricted by exogenous IFNs, suggesting that enhanced innate immune evasion contributed to its effective spread.
LIFE SCIENCE ALLIANCE
(2023)
Article
Microbiology
Lorie Marchitto, Mehdi Benlarbi, Jeremie Prevost, Annemarie Laumaea, Jade Descoteaux-Dinelle, Halima Medjahed, Catherine Bourassa, Gabrielle Gendron-Lepage, Frank Kirchhoff, Daniel Sauter, Beatrice H. Hahn, Andres Finzi, Jonathan Richard
Summary: HIV-1 evades antibody-dependent cellular cytotoxicity (ADCC) responses by downregulating the ligands of SLAM receptors, including NTB-A and 2B4. Vpu-mediated downregulation of CD48, the ligand of 2B4, prevents NK cell degranulation and contributes to ADCC evasion by HIV-1. This finding is important for understanding the mechanisms used by HIV-1 to evade ADCC.
Article
Multidisciplinary Sciences
Chiara Pastorio, Sabrina Noettger, Rayhane Nchioua, Fabian Zech, Konstantin M. J. Sparrer, Frank Kirchhoff
Summary: Additional mutations in the Spike protein of SARS-CoV-2 Omicron subvariants BA.2.12.1 and BA.4/5 help them outcompete the parental BA.2 subvariant. These mutations affect the infectivity, fusogenicity, and immune evasion of the virus, explaining the dominance and increased pathogenicity of these Omicron subvariants.
Letter
Biochemistry & Molecular Biology
Fabian Zech, Stefanie Weber, Hanna Dietenberger, Linyun Zhang, Sabrina Noettger, Meta Volcic, Tim Bergner, Clarissa Read, Konstantin M. J. Sparrer, Thomas F. E. Barth, Frank Kirchhoff
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)