Article
Virology
Manabu Igarashi, Takatsugu Hirokawa, Yoshihiro Takadate, Ayato Takada
Summary: This study utilized molecular modeling and molecular dynamics simulations to investigate the structures of NPC1 complexed with GPcls of Ebola virus, Sudan virus, and Marburg virus. Similar binding structures were observed in the complexes of EBOV and SUDV, while differences were found in the RAVV complex. These structural variances may impact the size and shape of the receptor-binding pocket of GPcl, providing valuable insights for understanding host preference differences among filoviruses and contributing to structure-based drug design.
Article
Medicine, Research & Experimental
Anna Scotto Rosato, Einar K. Krogsaeter, Dawid Jaslan, Carla Abrahamian, Sandro Montefusco, Chiara Soldati, Barbara Spix, Maria Teresa Pizzo, Giuseppina Grieco, Julia Boeck, Amanda Wyatt, Daniela Wuenkhaus, Marcel Passon, Marc Stieglitz, Marco Keller, Guido Hermey, Sandra Markmann, Doris Gruber-Schoffnegger, Susan Cotman, Ludger Johannes, Dennis Crusius, Ulrich Boehm, Christian Wahl-Schott, Martin Biel, Franz Bracher, Elvira De Leonibus, Elena Polishchuk, Diego L. Medina, Dominik Paquet, Christian Grimm
Summary: This study found that TPC2 activation can improve cellular phenotypes associated with LSDs, including cholesterol or lipofuscin accumulation and abnormal vacuole formation. Validation in patient cells and mouse models suggests that TPC2 is a promising target for the treatment of different types of LSDs.
EMBO MOLECULAR MEDICINE
(2022)
Review
Chemistry, Medicinal
Marcos Morales-Tenorio, Tiziana Ginex, Miguel Angel Cuesta-Geijo, Nuria E. Campillo, Cesar Munoz-Fontela, Covadonga Alonso, Rafael Delgado, Carmen Gil
Summary: The Niemann-Pick C1 (NPC1) receptor plays a crucial role in regulating intracellular cholesterol trafficking and facilitating the entry of Ebola virus into host cells. Disruption of the NPC1/EBOV-GP interaction could be a promising strategy for developing drugs to inhibit viral entry and infection, although further research is needed to understand the molecular and structural details of this interaction.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Shiqian Han, Qijun Wang, Yongfeng Song, Mao Pang, Chunguang Ren, Jing Wang, Dongwei Guan, Wei Xu, Fangyong Li, Fengchao Wang, Xinyuan Zhou, Carlos Fernandez-Hernando, Huiwen Zhang, Dianqing Wu, Zhijia Ye
Summary: Niemann-Pick disease type C (NP-C) is a genetic lysosomal disorder with limited therapeutic options. This study demonstrates that lithium treatment improves phenotypes and extends survival in NP-C mouse models by suppressing STING activation, SREBP2 processing, and target gene expression. Lithium impedes STING/SREBP2 transport, providing a mechanistic explanation for its effects. This reveals a potential therapeutic option for NP-C patients and a strategy to reduce active STING/SREBP2 pathway.
Review
Cell Biology
Irfan Ahmad, Seyede Narges Fatemi, Mohammad Ghaheri, Ali Rezvani, Dorsa Azizi Khezri, Mohammad Natami, Saman Yasamineh, Omid Gholizadeh, Zahra Bahmanyar
Summary: Viruses communicate with their hosts through interactions with proteins, lipids, and carbohydrates on the plasma membrane. The large endo/lysosomal membrane protein Niemann-Pick C1 (NPC1) is an essential intracellular receptor for viral infection and a potential therapeutic target for treating viral illnesses. NPC1 plays a crucial role in viral entry, replication, and infection by controlling cholesterol levels.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Biochemical Research Methods
Wenping Li, Melissa R. R. Pergande, Christopher A. A. Crutchfield, Brian C. C. Searle, Peter S. S. Backlund, Jaqueline A. A. Picache, Kathryn Burkert, Nicole M. M. Yanjanin-Farhat, Paul S. S. Blank, Cynthia L. L. Toth, Christopher A. A. Wassif, Forbes D. D. Porter, Stephanie M. M. Cologna
Summary: Niemann-Pick, type C1 (NPC1) is a fatal, neurodegenerative disease characterized by endo/lysosomal accumulation of unesterified cholesterol and sphingolipids. In this study, CSF samples from NPC1 individuals and controls were used to identify protein biomarkers. Pro-neuropeptide Y (NPY) was found to be significantly increased in NPC1 individuals, but levels were comparable to controls in individuals treated with miglustat. NPY could be a potential therapeutic target for NPC1 due to its roles in attenuating neuroinflammation and reducing excitotoxicity.
Article
Multidisciplinary Sciences
Ting-Ting Chu, Xintao Tu, Kun Yang, Jianjun Wu, Joyce J. Repa, Nan Yan
Summary: This study identifies a cGAS- and cGAMP-independent mode of STING activation that affects neuropathology and provides a therapeutic target for the treatment of Niemann-Pick disease type C.
Article
Pharmacology & Pharmacy
Isabel Garcia-Dorival, Miguel Angel Cuesta-Geijo, Lucia Barrado-Gil, Inmaculada Galindo, Urtzi Garaigorta, Jesus Urquiza, Ana del Puerto, Nuria E. Campillo, Ana Martinez, Pablo Gastaminza, Carmen Gil, Covadonga Alonso
Summary: The study found a novel interaction between the SARSCoV-2 nucleoprotein (N) and the cholesterol transporter NPC1, and identified compounds that can reduce viral infection, highlighting the importance of NPC1 for SARS-CoV-2 infection and suggesting a potential new therapeutic target against COVID-19.
ANTIVIRAL RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Jiang Du, Xinlei Liu, Yan Zhang, Xiaojing Han, Chunya Ma, Yanli Liu, Lihong Guan, Liang Qiao, Juntang Lin
Summary: This study found that combination treatment with HP beta CD and metformin did not prolong survival time or increase body weight in Npc1(-/-) mice, but it reduced inflammatory response.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biology
Cristin D. Davidson, Alana L. Gibson, Tansy Gu, Laura L. Baxter, Benjamin E. Deverman, Keith Beadle, Arturo A. Incao, Jorge L. Rodriguez-Gil, Hideji Fujiwara, Xuntian Jiang, Randy J. Chandler, Daniel S. Ory, Viviana Gradinaru, Charles P. Venditti, William J. Pavan
Summary: Niemann-Pick C1 disease (NPC1) is a rare, fatal neurodegenerative disease caused by mutations in NPC1 gene, resulting in cholesterol accumulation in lysosomes and leading to neurological complications. AAV-PHP.B vector shows greater efficiency in transducing the central nervous system of Npc1 mutant mice compared to AAV9, indicating potential for improved gene therapy in NPC1.
LIFE SCIENCE ALLIANCE
(2021)
Article
Genetics & Heredity
Jorge L. Rodriguez-Gil, Simona E. Bianconi, Nicole Farhat, David E. Kleiner, Marie Nelson, Forbes D. Porter
Summary: Niemann-Pick disease type C (NPC) is a rare and fatal disorder characterized by neurodegeneration and hepatic involvement. Patients with NPC have an increased risk of hepatocellular carcinoma, suggesting the need for screening in this population.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Article
Biochemistry & Molecular Biology
Carsten Holzmann, Martin Witt, Arndt Rolfs, Veronica Antipova, Andreas Wree
Summary: In a mouse model of Niemann-Pick disease type C1 (NPC1), combination treatment (COMBI) and individual treatments with MIGLU or HPssCD were beneficial in terms of body and brain weight, with differences observed based on gender. While all treatments had some beneficial effects on evaluated parameters, locomotor activity reduction was not significantly improved.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Martijn J. C. van der Lienden, Jan Aten, Andre R. A. Marques, Ingeborg S. E. Waas, Per W. B. Larsen, Nike Claessen, Nicole N. van der Wel, Roelof Ottenhoff, Marco van Eijk, Johannes M. F. G. Aerts
Summary: Niemann-Pick type C (NPC) disease is caused by impaired cholesterol efflux from lysosomes, and deficiency in lysosomal proteins like NPC1 may lead to abnormal levels of GCase and GBA2, as well as markers of lipid-stressed macrophages in the liver. The overexpression of LIMP2 in hepatocytes of NPC1(-/-) liver suggests a potential role in cholesterol export and protection of hepatocytes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Laura L. Baxter, Dawn E. Watkins-Chow, Nicholas L. Johnson, Nicole Y. Farhat, Frances M. Platt, Ryan K. Dale, Forbes D. Porter, William J. Pavan, Jorge L. Rodriguez-Gil
Summary: This study validates the use of LysoTracker as a predictor for age of onset and disease severity in NPC1 patients, using primary fibroblasts from a large cohort. The study also identifies a set of genes significantly associated with lysosomal defects or age of onset, particularly neurological symptom onset, and shows distinct expression patterns of these genes among patient subgroups.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Pilar Guatibonza Moreno, Luba M. M. Pardo, Catarina Pereira, Sabine Schroeder, Deepthi Vagiri, Ligia S. S. Almeida, Carlos Juaristi, Heba Hosny, Clarice C. Y. Loh, Anika Leubauer, Galina Torres Morales, Sebastian Oppermann, Marius-Ionut Iurascu, Steffen Fischer, Tara-Marisa Steinicke, Nikenza Viceconte, Claudia Cozma, Krishna Kumar Kandaswamy, Jorge Pinto Basto, Tobias Boettcher, Peter Bauer, Aida Bertoli-Avella
Summary: Niemann-Pick type C1 disease is a rare and severe autosomal recessive disorder characterized by neurovisceral clinical manifestations. This study analyzed the clinical, genetic, and biomarker data of 602 patients diagnosed with NPC1, finding that biomarkers may indicate disease severity and progression.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Review
Microbiology
Cesar Munoz-Fontela, Lina Widerspick, Randy A. Albrecht, Martin Beer, Miles W. Carroll, Emmie de Wit, Michael S. Diamond, William E. Dowling, Simon G. P. Funnell, Adolfo Garcia-Sastre, Nora M. Gerhards, Rineke de Jong, Vincent J. Munster, Johan Neyts, Stanley Perlman, Douglas S. Reed, Juergen A. Richt, Ximena Riveros-Balta, Chad J. Roy, Francisco J. Salguero, Michael Schotsaert, Lauren M. Schwartz, Robert A. Seder, Joaquim Segales, Seshadri S. Vasan, Ana Maria Henao-Restrepo, Dan H. Barouch
Summary: Animal models play a crucial role in evaluating the virulence, transmission, and immune escape of SARS-CoV-2 variants and are continuously being improved to better replicate the demographic characteristics of COVID-19.
Article
Microbiology
Julia R. Port, Claude Kwe Yinda, Victoria A. Avanzato, Jonathan E. Schulz, Myndi G. Holbrook, Neeltje van Doremalen, Carl Shaia, Robert J. Fischer, Vincent J. Munster
Summary: The major transmission route for SARS-CoV-2 is airborne. Experimental evidence shows that the Alpha variant has a higher competition advantage in airborne transmission compared to lineage A.
NATURE MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Neeltje van Doremalen, Manmeet Singh, Taylor A. Saturday, Claude Kwe Yinda, Lizzette Perez-Perez, W. Forrest Bohler, Zachary A. Weishampel, Matthew Lewis, Jonathan E. Schulz, Brandi N. Williamson, Kimberly Meade-White, Shane Gallogly, Atsushi Okumura, Friederike Feldmann, Jamie Lovaglio, Patrick W. Hanley, Carl Shaia, Heinz Feldmann, Emmie de Wit, Vincent J. Munster, Kyle Rosenke
Summary: In rhesus macaque model, disease severity and viral loads were lower in those inoculated with Omicron VOC compared to Delta VOC, suggesting reduced clinical disease caused by Omicron.
Article
Infectious Diseases
Andrea Marzi, Paige Fletcher, Friederike Feldmann, Greg Saturday, Patrick W. Hanley, Heinz Feldmann
Summary: This study aimed to develop an emergency vaccine against Sudan virus (SUDV) outbreaks. The results showed that the Sudan virus-specific vaccine effectively protected non-human primates from lethal SUDV infection. Additionally, previous vaccination with the Ebola virus vaccine had little cross-protective effect against SUDV challenge.
Article
Pathology
H. Nida Sen, Kevin M. Vannella, Yujuan Wang, Joon-Yong Chung, Shilpa Kodati, Sabrina C. Ramelli, Jung Wha Lee, Paola Perez, Sydney R. Stein, Alison Grazioli, James M. Dickey, Kris Ylaya, Manmeet Singh, Kwe Claude Yinda, Andrew Platt, Marcos J. Ramos-Benitez, Christa Zerbe, Vincent J. Munster, Emmie de Wit, Blake M. Warner, Daniel L. Herr, Joseph Rabin, Kapil K. Saharia, David E. Kleiner, Stephen M. Hewitt, Chi-Chao Chan, Daniel S. Chertowt
Summary: This study evaluated the pathology and cellular localization of SARS-CoV-2 in ocular tissues through autopsy. It found histopathologic abnormalities in ocular tissues and identified the localization of SARS-CoV-2 RNA in multiple cell types. Further studies are needed to determine the cause of these alterations.
AMERICAN JOURNAL OF PATHOLOGY
(2023)
Editorial Material
Immunology
Andrea Marzi, Heinz Feldmann
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Immunology
John Tyler Manning, Junki Maruyama, Timothy Wanninger, Rachel A. Reyna, Heather L. Stevenson, Bi-Hung Peng, Emily K. Mantlo, Cheng Huang, Slobodan Paessler
Summary: Junin virus, the cause of Argentine hemorrhagic fever, can be attenuated through specific mutations in the glycoprotein precursor gene. Early mutations attenuate the visceral disease and enhance immunogenicity in guinea pigs, while a specific mutation within an N-linked glycosylation motif is necessary for complete attenuation and enhanced immunogenicity of the Candid#1 vaccine strain.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Medicine, General & Internal
Kyle L. O'Donnell, Friederike Feldmann, Benjamin Kaza, Chad S. Clancy, Patrick W. Hanley, Paige Fletcher, Andrea Marzi
Summary: Marburg virus (MARV) is a highly pathogenic agent with no available treatments or vaccines. This study demonstrates that a vesicular stomatitis virus (VSV)-based vaccine expressing the MARV-Angola glycoprotein has a potential as a viable and fast-acting MARV vaccine candidate, providing uniform protection against the virus when administered in lower doses.
Editorial Material
Medicine, General & Internal
Kyle L. O'Donnell, Andrea Marzi
Review
Immunology
Takeshi Saito, Rachel A. A. Reyna, Satoshi Taniguchi, Kirsten Littlefield, Slobodan Paessler, Junki Maruyama
Summary: The Arenaviridae family includes viruses that cause severe and often fatal diseases in humans. High-containment facilities are required to handle these highly pathogenic viruses. The development of vaccines is essential for combating arenavirus infections, but currently there are limited options available. We provide a summary of the recent updates on vaccine candidates against these viruses.
Article
Virology
Miyuki Kimura, Risa Matsuoka, Satoshi Taniguchi, Junki Maruyama, Slobodan Paessler, Saori Oka, Atsushi Yamashita, Takasuke Fukuhara, Yoshiharu Matsuura, Hideki Tani
Summary: Through screening drug libraries, CB1 antagonists were found to effectively inhibit the entry of Lujo virus into cells and reduce infectivity. These findings provide promising candidate drugs for the treatment of Lujo virus infections.
Article
Multidisciplinary Sciences
Julia R. Port, Claude Kwe Yinda, Jade C. Riopelle, Zachary A. Weishampel, Taylor A. Saturday, Victoria A. Avanzato, Jonathan E. Schulz, Myndi G. Holbrook, Kent Barbian, Rose Perry-Gottschalk, Elaine Haddock, Craig Martens, Carl. I. Shaia, Teresa Lambe, Sarah C. Gilbert, Neeltje van Doremalen, Vincent J. Munster
Summary: Limited data is available on the effect of vaccination and previous virus exposure on the nature of SARS-CoV-2 transmission and immune-pressure on variants. A study found that transmission efficacy was reduced by approximately 60% in hamsters vaccinated via the intramuscular route and by 80% in previously infected hamsters and those vaccinated via the intranasal route. Additionally, the Omicron B.1.1.529 variant showed increased competitiveness in groups with pre-existing immunity against the Delta B.1.617.2 variant. These findings highlight the importance of improving vaccination strategies.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Cecilia A. Prator, Brianna M. Dorratt, Kyle L. O'Donnell, Justin Lack, Amanda N. Pinski, Stacy Ricklefs, Craig A. Martens, Ilhem Messaoudi, Andrea Marzi
Summary: This study found that infection with Marburg virus causes a highly fatal disease in humans, with no currently available vaccines or therapeutics. However, a low dose of the VSV-MARV vaccine has shown promise in protecting nonhuman primates from the disease. This suggests that the low dose VSV-MARV vaccine could be a beneficial option in public health efforts during future outbreaks.
EMERGING MICROBES & INFECTIONS
(2023)
Article
Multidisciplinary Sciences
Mackenzie Zendt, Fausto A. Bustos Carrillo, Sophie Kelly, Taylor Saturday, Maureen Degrange, Anita Ginigeme, Lurline Wu, Viviane Callier, Ana Ortega-Villa, Mondreakest Faust, Emma Chang-Rabley, Kara Bugal, Heather Kenney, Pavel Khil, Jung-Ho Youn, Gloria Osei, Pravesh Regmi, Victoria Anderson, Marita Bosticardo, Janine Daub, Thomas Dimaggio, Samantha Kreuzburg, Francesca Pala, Justina Pfister, Jennifer Treat, Jean Ulrick, Maria Karkanitsa, Heather Kalish, Douglas B. Kuhns, Debra L. Priel, Danielle L. Fink, John S. Tsang, Rachel Sparks, Gulbu Uzel, Meryl A. Waldman, Christa S. Zerbe, Ottavia M. Delmonte, Jenna R. E. Bergerson, Sanchita Das, Alexandra F. Freeman, Michail S. Lionakis, Kaitlyn Sadtler, Neeltje van Doremalen, Vincent Munster, Luigi D. Notarangelo, Steven M. Holland, Emily E. Ricotta
Summary: Research on coronavirus disease 2019 vaccination in immune-deficient/disordered people has primarily focused on cancer and organ transplantation populations. Three doses of the vaccine induced antispike IgG in most immune-deficient/disordered individuals, but additional doses are required for increased protection. The reduced IgG response to the Omicron BA.1 variant highlights the need for studying the efficacy of additional vaccinations, including bivalent vaccines, in this population.
Article
Multidisciplinary Sciences
Bharti Bhatia, Tsing-Lee Tang-Huau, Friederike Feldmann, Patrick W. Hanley, Rebecca Rosenke, Carl Shaia, Andrea Marzi, Heinz Feldmann
Summary: This study demonstrates the efficacy of a VSV-based vaccine in providing protection against KFDV and related diseases, and inducing cross-reactive immune responses.