Article
Microbiology
Wei Pan, Nie Hui, Hongmei Wang, Hongbin He
Summary: Bovine parainfluenza virus 3 enters MDBK cells via macropinocytosis and clathrin-mediated endocytosis, requiring acid-dependent entry and cathepsin L. Additionally, macropinocytosis is dependent on actin dynamics during BPIV3 infection.
VETERINARY MICROBIOLOGY
(2021)
Article
Virology
Wei Li, Ji Liu, Yuanyuan Liu, Qin Li, Wen Yin, Kevin K. Wanderi, Xiaowei Zhang, Zhiping Zhang, Xian-En Zhang, Zongqiang Cui
Summary: This study reveals the dynamic podosome-mediated entry of HIV-1 into macrophages, where the core and ring structures of podosomes play complex roles in viral entry, with the CCR5 coreceptor recruited to form specific clusters. The podosome facilitates HIV-1 entry with a rotation mode triggered by dynamic actin.
JOURNAL OF VIROLOGY
(2021)
Article
Multidisciplinary Sciences
David A. Swan, Morgane Rolland, Joshua T. Herbeck, Joshua T. Schiffer, Daniel B. Reeves
Summary: Modern HIV research relies heavily on viral sequencing and population measurements, and the study found that viral evolution during primary infection is mainly driven by the intrinsic fitness distribution rather than positive selection by the host adaptive immune system. The infectivity of mutant variants is primarily determined by an exponential distribution, with most variants being slightly less infectious than their parents.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biology
Xia Li, Dianbing Wang, Zongqiang Cui, Qin Li, Min Li, Yingxin Ma, Qinxue Hu, Yikai Zhou, Xian-En Zhang
Summary: Research suggests that HIV-1 may enter the nucleus through nuclear vesicles, revealing a new mechanism for HIV-1 nuclear entry and expanding our understanding of HIV-1 virology.
SCIENCE CHINA-LIFE SCIENCES
(2021)
Article
Immunology
Federica De Santis, Ana Borrajo Lopez, Sara Virtuoso, Noemi Poerio, Patrizia Saccomandi, Tommaso Olimpieri, Leonardo Duca, Lucia Henrici De Angelis, Katia Aquilano, Marco Maria D'Andrea, Stefano Aquaro, Alessandra Borsetti, Francesca Ceccherini-Silberstein, Maurizio Fraziano
Summary: This study found that phosphatidylcholine (PC) liposomes can reduce the entry of HIV into human macrophages by decreasing the expression of the CD4 receptor. This may have implications for HIV transmission and pathogenesis.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Microbiology
Shiqian Li, Dai Xiao, Luwen Zhang, Rui Chen, Daili Song, Yiping Wen, Rui Wu, Qin Zhao, Senyan Du, Qigui Yan, Sanjie Cao, Xiaobo Huang
Summary: Porcine deltacoronavirus (PDCoV) enters swine testicle (ST) cells via clathrin-mediated endocytosis, requiring the involvement of dynamin and cholesterol. Additionally, the transport of PDCoV in ST cells does not require the participation of the endosomal system.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biochemistry & Molecular Biology
David Wensel, Shawn Williams, David P. Dixon, Paris Ward, Patti McCormick, Nestor Concha, Eugene Stewart, Xuan Hong, Charles Mazzucco, Shreya Pal, Bo Ding, Christoph Fellinger, Mark Krystal
Summary: GSK3732394, a multi-specific biologic inhibitor of HIV entry, binds to CD4 and inhibits downstream actions of gp160. The adnectin interacts with domains D2-D3 of CD4, stabilizing a novel T-shaped conformation. Amino acid F202 forms a key interaction with the adnectin and L151 contributes to the specificity for binding to human CD4.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Chemistry, Medicinal
Takuya Kobayakawa, Kohei Tsuji, Kiju Konno, Ai Himeno, Ami Masuda, Tingting Yang, Kohei Takahashi, Yusuke Ishida, Nami Ohashi, Takeo Kuwata, Kaho Matsumoto, Kazuhisa Yoshimura, Hiromi Sakawaki, Tomoyuki Miura, Shigeyoshi Harada, Shuzo Matsushita, Hirokazu Tamamura
Summary: The study synthesized hybrid molecules of CD4 mimics and found that modification with a PEG unit was more suitable than a long alkyl chain, showing higher anti-HIV activity and lower cytotoxicity. In a rhesus macaque pharmacokinetics study, the hybrid compound had a better PK profile, with intramuscular injection being more effective than intravenous injection to maintain high blood concentration of the CD4 mimic.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Microbiology
Geraldine Vilmen, Anna C. Smith, Hector Cervera Benet, Rajni Kant Shukla, Ross C. Larue, Alon Herschhorn, Amit Sharma
Summary: Infection of rhesus macaques with simian-human immunodeficiency viruses (SHIVs) is a key model for vaccine development, but most circulating HIV-1 envelope glycoproteins cannot infect macaques. This study found that the conformational state of HIV-1 envelope glycoproteins is a major determinant for rhesus CD4 usage, viral-host membrane fusion, and SHIV replication.
Article
Microbiology
Geraldine Vilmen, Anna C. Smith, Hector Cervera Benet, Rajni Kant Shukla, Ross C. Larue, Alon Herschhorn, Amit Sharma
Summary: Infection of rhesus macaques with SHIVs encoding HIV-1 Envs is a common model for vaccine development, but the challenge lies in the fact that most circulating HIV-1 Envs do not efficiently use the rhesus CD4 receptor for viral entry. By altering the conformational state of HIV-1 Envs, open Env conformations can overcome this barrier and enhance SHIV replication in rhesus lymphocytes, indicating that the conformational state of the Env is crucial for SHIV replication and viral entry in rhesus macaques.
Article
Immunology
Pierre Gantner, Supranee Buranapraditkun, Amelie Pagliuzza, Caroline Dufour, Marion Pardons, Julie L. Mitchell, Eugene Kroon, Carlo Sacdalan, Nicha Tulmethakaan, Suteeraporn Pinyakorn, Merlin L. Robb, Nittaya Phanuphak, Jintanat Ananworanich, Denise Hsu, Sandhya Vasan, Lydie Trautmann, Remi Fromentin, Nicolas Chomont
Summary: During early stages of HIV infection, the virus initially targets a small population of proliferating memory CD4+ T cells with high surface expression of CCR5. Productively infected cells exhibit different phenotypes and TCR sequences depending on the stage of infection and location within the body. The TCR repertoire of infected cells is biased towards previously expanded and disseminated clones, suggesting independent infection events. Latent genetically intact proviruses are present early in infection, indicating simultaneous generation of latent infected cells.
Article
Microbiology
Laura P. Kincer, Sarah Beth Joseph, Maria M. Gilleece, Blake M. Hauser, Sabrina Sizemore, Shuntai Zhou, Clara Di Germanio, Henrik Zetterberg, Dietmar Fuchs, Steven G. Deeks, Serena Spudich, Magnus Gisslen, Richard W. Price, Ronald Swanstrom
Summary: HIV-1 can persist in a latent reservoir in individuals receiving antiretroviral therapy, and rebound virus can be detected in the cerebrospinal fluid during treatment interruption. In this study, we found that high viral loads and clonally amplified viral lineages in the cerebrospinal fluid were correlated with the influx of white blood cells. Additionally, we did not observe rebound macrophage-tropic virus in the cerebrospinal fluid, indicating that the CNS may not be a source of this virus. We propose a model in which R5 T cell-tropic virus is released from infected T cells in the CNS during treatment interruption.
NATURE MICROBIOLOGY
(2023)
Article
Immunology
Hongxia Yan, Tong Wu, Yue Chen, Hongliang Jin, Li Li, Yuanmei Zhu, Huihui Chong, Yuxian He
Summary: A bifunctional inhibitor, 2P23-iMab, was designed in this study by genetically conjugating a potent HIV fusion inhibitor, 2P23, to the scFv of ibalizumab. This new inhibitor showed significantly improved inhibitory activity against a broad panel of HIV-1 pseudoviruses and displayed potent activity against viruses resistant to iMab, T-20, or 2P23. The study provides insights into the development of novel bispecific HIV entry inhibitors with potent and broad-spectrum antiviral activity.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(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
Gustavo F. Contreras, Jonathan Saavedra, Nieves Navarro-Quezada, Guido Mellado, Carlos Gonzalez, Alan Neely
Summary: This study investigated the inhibition of Ca(V)2.3 channels by RGK proteins in the absence of CaV beta. It was found that only Gem protein had an effect, reducing the number of channels in the plasma membrane through enhanced endocytosis mediated by dynamin.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Letter
Hematology
Jan-Inge Henter, Egle Kvedaraite, Daniel Martin Munoz, Monica Cheng Munthe-Kaas, Bernward Zeller, Tove A. Nystad, Caroline Bjorklund, Isabella Donner, Magda Lourda, Henrik Zetterberg, Kaj Blennow, Nikolas Herold, Desiree Gavhed, Tatiana von Bahr Greenwood
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Letter
Immunology
Jessica Seessle, Tim Waterboer, Cora Freund, Barbara Muller, Uta Merle
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Pathology
Magali Merrien, Agata M. Wasik, Elin Ljung, Mohammad H. A. Morsy, Joana de Matos Rodrigues, Mattias Carlsten, Georgios Z. Rassidakis, Birger Christensson, Arne Kolstad, Mats Jerkeman, Sara Ek, Nikolas Herold, Bjorn E. Wahlin, Birgitta Sander
Summary: SAMHD1 is highly variably expressed in mantle cell lymphoma (MCL) patients, with higher levels in blastoid/pleomorphic cases and correlation to tumor cell proliferation. Despite its association with known adverse prognostic factors, the expression of SAMHD1 did not correlate with progression-free survival (PFS) or overall survival (OS) in MCL patients treated according to the Nordic MCL2 or MCL3 protocols.
Article
Virology
Chen Qian, Annica Flemming, Barbara Muller, Don C. Lamb
Summary: Researchers used fluorescence lifetime imaging microscopy and single virus tracking to study the processing of Gag protein in HIV-1 particles. They found that, in the majority of viral particles, processing of Gag protein occurs with a delay after particle assembly.
Article
Multidisciplinary Sciences
Hanna Renk, Alex Dulovic, Alina Seidel, Matthias Becker, Dorit Fabricius, Maria Zernickel, Daniel Junker, Ruediger Gross, Janis Mueller, Alexander Hilger, Sebastian F. N. Bode, Linus Fritsch, Pauline Frieh, Anneke Haddad, Tessa Goerne, Jonathan Remppis, Tina Ganzemueller, Andrea Dietz, Daniela Huzly, Hartmut Hengel, Klaus Kaier, Susanne Weber, Eva-Maria Jacobsen, Philipp D. Kaiser, Bjoern Traenkle, Ulrich Rothbauer, Maximilian Stich, Burkhard Toenshoff, Georg F. Hoffmann, Barbara Mueller, Carolin Ludwig, Bernd Jahrsdoerfer, Hubert Schrezenmeier, Andreas Peter, Sebastian Hoerber, Thomas Iftner, Jan Muench, Thomas Stamminger, Hans-Juergen Gross, Martin Wolkewitz, Corinna Engel, Weimin Liu, Marta Rizzi, Beatrice H. Hahn, Philipp Henneke, Axel R. Franz, Klaus-Michael Debatin, Nicole Schneiderhan-Marra, Ales Janda, Roland Elling
Summary: This study compares the humoral immune response in children and adults following SARS-CoV-2 infection and finds that children are more likely to have asymptomatic infections and higher levels of specific antibodies that persist for a longer time. Symptomatic and asymptomatic infections induce similar humoral responses across all age groups.
NATURE COMMUNICATIONS
(2022)
Article
Virology
Thorsten G. Mueller, Vojtech Zila, Barbara Muller, Hans-Georg Kraeusslich
Summary: Recent evidence suggests that reverse transcription and viral genome uncoating of HIV-1 occur in the nucleus rather than the cytoplasm. The cone-shaped capsid may play a crucial role in nuclear import of HIV-1. Rupture of the capsid may be triggered by completion of reverse transcription, nuclear factors, or physical damage, and is closely associated with the integration process.
ANNUAL REVIEW OF VIROLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Andrea Volpato, Dirk Ollech, Jonatan Alvelid, Martina Damenti, Barbara Mueller, Andrew G. York, Maria Ingaramo, Ilaria Testa
Summary: The authors introduce a method called STARSS, which uses reversible molecular transitions of switchable fluorescent proteins to resolve the rotational diffusion rate of large macromolecular complexes, thus extending the observable mass range. They applied STARSS to investigate the rotational mobility of several molecular complexes in cells.
NATURE BIOTECHNOLOGY
(2023)
Article
Oncology
Claudia M. Denkinger, Maike Janssen, Ulrike Schaekel, Julia Gall, Albrecht Leo, Patrick Stelmach, Stefan F. Weber, Johannes Krisam, Lukas Baumann, Jacek Stermann, Uta Merle, Markus A. Weigand, Christian Nusshag, Lars Bullinger, Jens-Florian Schrezenmeier, Martin Bornhaeuser, Nael Alakel, Oliver Witzke, Timo Wolf, Maria J. G. T. Vehreschild, Stefan Schmiedel, Marylyn M. Addo, Felix Herth, Michael Kreuter, Phil-Robin Tepasse, Bernd Hertenstein, Mathias Haenel, Anke Morgner, Michael Kiehl, Olaf Hopfer, Mohammad-Amen Wattad, Carl C. Schimanski, Cihan Celik, Thorsten Pohle, Matthias Ruhe, Winfried Kern, Anita Schmitt, Hanns-Martin Lorenz, Margarida Souto-Carneiro, Mary Gaeddert, Niels Halama, Stefan Meuer, Hans-Georg Kraeusslich, Barbara Mueller, Paul Schnitzler, Sylvia Parthe, Ralf Bartenschlager, Martina Gronkowski, Jennifer Klemmer, Michael Schmitt, Peter Dreger, Katharina Kriegsmann, Richard F. Schlenk, Carsten Muller-Tidow
Summary: Patients with cancer and compromised immune systems may benefit from convalescent/vaccinated plasma treatment to improve COVID-19 outcomes.
Article
Biochemistry & Molecular Biology
Lara Gallucci, Tobias Abele, Raffaele Fronza, Bettina Stolp, Vibor Laketa, Samy Sid Ahmed, Annica Flemming, Barbara Mueller, Kerstin Goepfrich, Oliver T. Fackler
Summary: Compared to 2D suspension cultures, 3D collagen as a tissue-like environment alters immature dendritic cell (iDC) properties and their response to HIV-1 infection. iDCs in 3D collagen have an elongated morphology with increased deformability, reduced HIV-1 particle uptake, and increased fusion efficiency. Adhesion to a 2D collagen matrix is sufficient to increase iDC deformability, HIV-1 receptor exposure, and permissivity to infection. These findings suggest that mechano-physical cues of 2D and 3D collagen environments regulate iDC function and shape divergent roles during HIV-1 infection.
Article
Hematology
Daniel W. Hagey, Egle Kvedaraite, Mira Akber, Andre Goergens, Joman Javadi, Tatiana von Bahr Greenwood, Caroline Bjorklund, Selma Olsson Akefeldt, Tova Hannegard-Hamrin, Henrik Arnell, Katalin Dobra, Nikolas Herold, Mattias Svensson, Samir El Andaloussi, Jan-Inge Henter, Magda Lourda
Summary: This study compared monocyte-derived dendritic cells from LCH patients to those from healthy controls or patients with Crohn's disease. The findings showed that LCH cells exhibited increased endo- and exocytosis gene activity and the enrichment of pathological transcripts in extracellular vesicles. The study also indicated that the LCH secretome had a significant effect on lymphocyte activity.
Article
Virology
Maximilian Stich, Louise Benning, Claudius Speer, Sven F. Garbade, Marie Bartenschlager, Heeyoung Kim, Kathrin Jeltsch, Julia Tabatabai, Moritz Niesert, Ales Janda, Hanna Renk, Roland Elling, Georg Friedrich Hoffmann, Hans-Georg Kraeusslich, Barbara Mueller, Ralf Bartenschlager, Burkhard Toenshoff
Summary: Data on cross-neutralization of the SARS-CoV-2 omicron variant more than 1 year after infection show that previous wild-type infection does not provide sufficient immunity against the omicron variant. Only a small percentage of unvaccinated individuals, including children and adolescents, had neutralizing activity against omicron, indicating the urgency of vaccination strategies. mRNA vaccination in convalescent adults significantly increased neutralization against both delta and omicron variants, but the neutralization of omicron was still lower than that of delta.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Biochemical Research Methods
Zeynep Cakir, Samuel J. Lord, Yuan Zhou, Gwendolyn M. Jang, Benjamin J. Polacco, Manon Eckhardt, David Jimenez-Morales, Billy W. Newton, Adam L. Orr, Jeffrey R. Johnson, Alexandre da Cruz, R. Dyche Mullins, Nevan J. Krogan, Robert W. Mahley, Danielle L. Swaney
Summary: Apolipoprotein E4 is the major genetic risk factor for Alzheimer's disease. Neuronal expression of apoE4 increases in response to stress and it disrupts VASP interactions with actin cytoskeletal and microtubular proteins, leading to cytoskeletal defects. Blocking the phosphorylation of VASP can restore cytoskeletal defects caused by apoE4.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Article
Oncology
Maria Sjoborg Alpman, Annica Jarting, Kerstin Magnusson, Aristomenis Manouras, Jan-Inge Henter, Agneta Mansson Broberg, Nikolas Herold
Summary: This study investigated the feasibility of different echocardiographic methods to evaluate left ventricular systolic function and the incidence of subclinical left ventricular dysfunction in childhood sarcoma patients. The results showed that more than 40% of the patients had impaired longitudinal strain, and most of them also had impairment of left ventricular ejection fraction or fractional shortening. Therefore, the inclusion of longitudinal strain in pediatric echocardiographic surveillance protocols is recommended.
Review
Oncology
Roelof van Ewijk, Morgane Cleirec, Nikolas Herold, Marie-Cecile le Deley, Natasha van Eijkelenburg, Pascaline Boudou-Rouquette, Severine Risbourg, Sandra J. Strauss, Emanuela Palmerini, Kjetil Boye, Leo Kager, Stefanie Hecker-Nolting, Antonin Marchais, Nathalie Gaspar
Summary: This study analyzed changes in phase II trials for recurrent/refractory osteosarcoma and found high heterogeneity in trial design, characteristics, and efficacy data. Despite an increase in the number of trials and changes in trial design, issues remain regarding patient selection, primary endpoints, and statistical hypotheses for osteosarcoma trials.
CANCER TREATMENT REVIEWS
(2023)
Meeting Abstract
Oncology
Jan-Inge Henter, Egle Kvedaraite, Daniel Martin Munoz, Monica Cheng Munthe-Kaas, Bernward Zeller, Tove Nystad, Caroline Bjorklund, Isabella Donner, Magda Lourda, Henrik Zetterberg, Kaj Blennow, Nikolas Herold, Desiree Gavhed, Tatiana von Bahr Greenwood
PEDIATRIC BLOOD & CANCER
(2022)