Article
Biology
Lenka Stejskal, Mphatso D. Kalemera, Charlotte B. Lewis, Machaela Palor, Lucas Walker, Tina Daviter, William D. Lees, David S. Moss, Myrto Kremyda-Vlachou, Zisis Kozlakidis, Giulia Gallo, Dalan Bailey, William Rosenberg, Christopher J. R. Illingworth, Adrian J. Shepherd, Joe Grove
Summary: This study reveals that the hypervariable region-1 (HVR-1) of the fusion proteins E1E2 in Hepatitis C Virus (HCV) has an autoinhibitory function that controls the activity of the proteins. The mechanism is turned off by host receptor interactions, allowing virus entry. Mutations or deletion of HVR-1 results in enhanced virus entry but increased sensitivity to neutralising antibodies.
Article
Cell Biology
Georgia Papadopoulou, Stavroula Petroulia, Eirini Karamichali, Alexios Dimitriadis, Dimitrios Marousis, Elisavet Ioannidou, Panagiota Papazafiri, John Koskinas, Pelagia Foka, Urania Georgopoulou
Summary: Hepatitis C virus (HCV) alters gene expression epigenetically to rearrange the cellular microenvironment in a beneficial way for its life cycle. Lysine-specific demethylase 1 (LSD1) is an epigenetic controller of critical cellular functions that are essential for HCV propagation. This study investigates the role of LSD1 in HCV infection and shows that LSD1 overexpression inhibits HCV replication, while inhibition of LSD1 increases viral replication. The study also suggests that LSD1 participates in an antiviral mechanism by activating IFITM3 via demethylation, leading to degradation of HCV virions.
Article
Virology
Takayuki Abe, Yuki Marutani, Lin Deng, Chieko Matsui, Masayoshi Fukasawa, Ryosuke Suzuki, Takaji Wakita, Yoshiharu Matsuura, Ikuo Shoji
Summary: Host cells have defense mechanisms to restrict viral infection, but viruses have counteracting strategies to infect. This study found that ANX5 and PKC isoforms, including PKC alpha and PKC eta, play a role in suppressing HCV infection by regulating OCLN integrity. Disruption of OCLN integrity increases HCV infection, and HCV disrupts ANX5-mediated OCLN integrity by downregulating PKC alpha and PKC eta expression to promote viral infection.
JOURNAL OF VIROLOGY
(2023)
Article
Virology
Kamilla Toon, Mphatso D. Kalemera, Machaela Palor, Nicola J. Rose, Yasuhiro Takeuchi, Joe Grove, Giada Mattiuzzo
Summary: Due to increased and broadened screening efforts, the number of viral species in the Hepacivirus genus has rapidly expanded. Genetic features of hepaciviruses suggest they have adapted and evolved to hijack host proteins for efficient liver propagation. A study on GB virus B (GBV-B) found that claudin-1 is an essential entry factor, shared with hepatitis C virus (HCV), but with distinct mechanisms of entry. Understanding the molecular mechanisms of hepacivirus entry can inform the design of new vaccines and treatments targeting the first stage of HCV infection.
JOURNAL OF VIROLOGY
(2023)
Article
Virology
Michael P. Schwoerer, Alexander Ploss
Summary: HCV is unable to infect mice due to incompatibility with host factors, the presence of dominant restriction factors, and effective immune responses. Understanding these limitations will help in developing an immunocompetent mouse model that can fully support HCV infection and exhibit disease similar to that of infected humans.
CURRENT OPINION IN VIROLOGY
(2022)
Article
Microbiology
Becky H. Lee, Giulia Tebaldi, Suzanne M. Pritchard, Anthony Nicola
Summary: This study demonstrates the importance of the NEDD8 cascade in the internalization of HSV-1 and HSV-2, while having minimal effect on the entry of veterinary viruses. The results provide new insights into the cellular processes involved in HSV internalization.
MICROBIOLOGY SPECTRUM
(2022)
Article
Multidisciplinary Sciences
Ashish Kumar, Tiana C. Rohe, Elizabeth J. Elrod, Abdul G. Khan, Altaira D. Dearborn, Ryan Kissinger, Arash Grakoui, Joseph Marcotrigiano
Summary: Hepatitis C virus (HCV) uses a hybrid entry mechanism involving the release of an internal loop from envelope glycoprotein E2 upon exposure to low pH. The amino terminal region of E2 is found to be critical for interaction with the host membrane, suggesting its importance in the HCV entry mechanism.
NATURE COMMUNICATIONS
(2023)
Review
Microbiology
Emmanuelle V. LeBlanc, Youjin Kim, Chantelle J. Capicciotti, Che C. Colpitts
Summary: This review provides an overview of the roles of viral and cellular glycans in HCV infection and highlights advances in the development of entry inhibitors and vaccines to effectively prevent HCV infection.
Article
Biochemistry & Molecular Biology
Hyung Chul Ryu, Marc Windisch, Jee Woong Lim, Inhee Choi, Eun Kyu Lee, Hye Hyun Yoo, Tae Kon Kim
Summary: Novel small-molecule inhibitors of hepatitis C virus (HCV) were synthesized and screened, with J2H-1701 identified as the optimized lead compound for HCV entry inhibition based on its potent antiviral activity and safety profile. This compound showed effective multi-genotypic antiviral activity and potential interaction with the HCV E2 glycoprotein, suggesting it as a candidate drug for HCV entry inhibition.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Article
Immunology
Siddharth Sridhar, Cyril Chik-Yan Yip, Kelvin Hon-Yin Lo, Shusheng Wu, Jianwen Situ, Nicholas Foo-Siong Chew, Kit-Hang Leung, Helen Shuk-Ying Chan, Sally Cheuk-Ying Wong, Anthony Wai-Shing Leung, Cindy Wing-Sze Tse, Kitty S. C. Fung, Owen Tak-Yin Tsang, Kam-Lun Hon, Vincent Chi-Chung Cheng, Ken Ho-Leung Ng, Kwok-Yung Yuen
Summary: This study investigated human HEV-C1 infections detected in Hong Kong, with a focus on outcomes in immunocompromised individuals. The findings showed that immunocompromised HEV-C1-infected patients frequently progress to persistent HEV-C1 infection, for which ribavirin is a suitable treatment option.
CLINICAL INFECTIOUS DISEASES
(2022)
Review
Microbiology
Anshuman Das, Efrain E. Rivera-Serrano, Xin Yin, Christopher M. Walker, Zongdi Feng, Stanley M. Lemon
Summary: In this Review, the authors discuss quasi-enveloped virions, their entry and release from human host cells, and their impact on host immunity and pathogenesis. They focus on hepatitis A and E viruses, which were previously considered non-enveloped but are now known to be released as quasi-enveloped virions cloaked in host membranes. Despite lacking virally encoded proteins on their surface, these virions efficiently enter cells and replicate. The authors also describe the mechanisms by which specific peptide sequences in the capsids of these virions mediate their release from hepatocytes and the current understanding of their cell entry mechanism.
NATURE REVIEWS MICROBIOLOGY
(2023)
Review
Gastroenterology & Hepatology
Hui-Chun Li, Chee-Hing Yang, Shih-Yen Lo
Summary: HCV, an obligatory intracellular pathogen, relies heavily on host cells for successful propagation. Its lifecycle includes stages such as viral entry, protein translation, RNA replication, viral assembly, and release, with hundreds of cellular factors identified over three decades of research. These factors, some of which are targeted for anti-HCV therapies, provide valuable insight into HCV replication strategies.
WORLD JOURNAL OF GASTROENTEROLOGY
(2021)
Review
Virology
Chui-Wa So, Glenn Randall
Summary: Hepatocytes, the main target of HCV, require extensive trafficking in polarized cells for infection. Researchers are utilizing three-dimensional cell culture models resembling in vivo hepatocytes to study HCV infection.
Article
Microbiology
Ahmed K. Oraby, Cassandra L. Gardner, Robert F. Needle, Hassan M. Kofahi, Kylie R. Everard, Nathan G. A. Taylor, Suzette G. Rutihinda, Jacqueline P. Barry, Kensuke Hirasawa, Paris E. Georghiou, Rodney S. Russell
Summary: The novel small-molecule compound AO13 demonstrated a consistent but low-level antiviral effect against HCV, potentially acting on a late stage in the viral life cycle. This compound could serve as a lead compound for future drug development against other important viruses.
MICROBIOLOGY SPECTRUM
(2021)
Article
Gastroenterology & Hepatology
Penglei Jiang, Hongyu Jia, Xinyue Qian, Tian Tang, Yingli Han, Zhaoru Zhang, Lingli Jiang, Zebin Yu, Lin Zheng, Guodong Yu, Huan Cai, Shanyan Zhang, Xiaoli Zhang, Jueqing Gu, Chanyuan Ye, Lisha Yang, Yingfeng Lu, Heng Liu, Xiaoqing Lu, Ciliang Jin, Yue Ren, Miaomiao Lu, Lingling Xu, Jiong Yu, Xi Jin, Yida Yang, Pengxu Qian
Summary: This study used single-cell RNA sequencing to investigate the transcriptomic landscape of peripheral immune cells in CHB patients before and after PegIFN-alpha therapy. The study identified specific cell subsets associated with CHB and found that PegIFN-alpha treatment could decrease hyperactivated monocytes, increase long-lived naive/memory T cells, and enhance effector T cell cytotoxicity. Furthermore, the treatment altered the transcriptional profiles of immune cells and enhanced innate antiviral response.
Article
Microbiology
Shashank Tripathi, Vinod R. M. T. Balasubramaniam, Julia A. Brown, Ignacio Mena, Alesha Grant, Susana V. Bardina, Kevin Maringer, Megan C. Schwarz, Ana M. Maestre, Marion Sourisseau, Randy A. Albrecht, Florian Krammer, Matthew J. Evans, Ana Fernandez-Sesma, Jean K. Lim, Adolfo Garcia-Sastre
Article
Virology
Marion Sourisseau, Daniel J. P. Lawrence, Megan C. Schwarz, Carina H. Storrs, Ethan C. Veit, Jesse D. Bloom, Matthew J. Evans
JOURNAL OF VIROLOGY
(2019)
Article
Chemistry, Medicinal
Ryan O'Hanlon, Victor H. Leyva-Grado, Marion Sourisseau, Matthew J. Evans, Megan L. Shaw
ACS INFECTIOUS DISEASES
(2019)
Article
Immunology
Benjamin Israelow, Eric Song, Tianyang Mao, Peiwen Lu, Amit Meir, Feimei Liu, Mia Madel Alfajaro, Jin Wei, Huiping Dong, Robert J. Homer, Aaron Ring, Craig B. Wilen, Akiko Iwasaki
JOURNAL OF EXPERIMENTAL MEDICINE
(2020)
Article
Multidisciplinary Sciences
Takehiro Takahashi, Mallory K. Ellingson, Patrick Wong, Benjamin Israelow, Carolina Lucas, Jon Klein, Julio Silva, Tianyang Mao, Ji Eun Oh, Maria Tokuyama, Peiwen Lu, Arvind Venkataraman, Annsea Park, Feimei Liu, Amit Meir, Jonathan Sun, Eric Y. Wang, Arnau Casanovas-Massana, Anne L. Wyllie, Chantal B. F. Vogels, Rebecca Earnest, Sarah Lapidus, Isabel M. Ott, Adam J. Moore, Albert Shaw, John B. Fournier, Camila D. Odio, Farhadian Shelli, Charles Dela Cruz, Nathan D. Grubaugh, Wade L. Schulz, Aaron M. Ring, Albert Ko, Saad B. Omer, Akiko Iwasaki
Article
Biochemistry & Molecular Biology
Eriko Kudo, Benjamin Israelow, Chantal B. F. Vogels, Peiwen Lu, Anne L. Wyllie, Maria Tokuyama, Arvind Venkataraman, Doug E. Brackney, Isabel M. Ott, Mary E. Petrone, Rebecca Earnest, Sarah Lapidus, M. Catherine Muenker, Adam J. Moore, Arnau Casanovas-Massana, Saad B. Omer, Charles S. Dela Cruz, Shelli F. Farhadian, Albert I. Ko, Nathan D. Grubaugh, Akiko Iwasaki
Article
Immunology
Eric Song, Ce Zhang, Benjamin Israelow, Alice Lu-Culligan, Alba Vieites Prado, Sophie Skriabine, Peiwen Lu, Orr-El Weizman, Feimei Liu, Yile Dai, Klara Szigeti-Buck, Yuki Yasumoto, Guilin Wang, Christopher Castaldi, Jaime Heltke, Evelyn Ng, John Wheeler, Mia Madel Alfajaro, Etienne Levavasseur, Benjamin Fontes, Neal G. Ravindra, David Van Dijk, Shrikant Mane, Murat Gunel, Aaron Ring, Syed A. Jaffar Kazmi, Kai Zhang, Craig B. Wilen, Tamas L. Horvath, Isabelle Plu, Stephane Haik, Jean-Leon Thomas, Angeliki Louvi, Shelli F. Farhadian, Anita Huttner, Danielle Seilhean, Nicolas Renier, Kaya Bilguvar, Akiko Iwasaki
Summary: The study showed through three approaches that SARS-CoV-2 is capable of infecting brain neurons, leading to metabolic changes and pathological features without triggering type I interferon responses. These results provide evidence for the neuroinvasive capacity of SARS-CoV-2 and the unexpected consequence of direct infection of neurons by the virus.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Yuping Cai, Daniel J. Kim, Takehiro Takahashi, David Broadhurst, Hong Yan, Shuangge Ma, Nicholas J. W. Rattray, Arnau Casanovas-Massana, Benjamin Israelow, Jon Klein, Carolina Lucas, Tianyang Mao, Adam J. Moore, M. Catherine Muenker, Ji Eun Oh, Julio Silva, Patrick Wong, Albert Ko, Sajid A. Khan, Akiko Lwasaki, Caroline H. Johnson
Summary: This study reveals a specific link between the serum metabolomes and immune responses in male COVID-19 patients, with the metabolite kynurenic acid (KA) playing a key role in influencing clinical outcomes and immune responses in a sex-specific manner.
Article
Microbiology
Min Zhao, Pei-Yi Su, Danielle A. Castro, Therese N. Tripler, Yingxia Hu, Matthew Cook, Albert Ko, Shelli F. Farhadian, Benjamin Israelow, Charles S. Dela Cruz, Yong Xiong, Richard E. Sutton
Summary: A novel cell fusion assay based on spike-hACE2 interaction was developed, showing good correlation with standard pseudotyping for inhibition by convalescent sera, cloned antibodies, and biologics. The assay is easy to implement and may serve as the basis for high throughput screens to identify inhibitors of SARS-CoV-2 virus-cell binding and entry.
Article
Immunology
Benjamin Israelow, Tianyang Mao, Jonathan Klein, Eric Song, Bridget Menasche, Saad B. Omer, Akiko Iwasaki
Summary: Research demonstrates that both humoral and cellular immunity play a role in clearing SARS-CoV-2, and convalescent mice or mice vaccinated with mRNA are protected from infection with both the wild type virus and the B.1.351 variant. This protection is mainly mediated by antibody response rather than cellular immunity.
SCIENCE IMMUNOLOGY
(2021)
Article
Immunology
Tianyang Mao, Benjamin Israelow, Carolina Lucas, Chantal B. F. Vogels, Maria Luisa Gomez-Calvo, Olga Fedorova, Mallery Breban, Bridget L. Menasche, Huiping Dong, Melissa Linehan, Craig B. Wilen, Marie L. Landry, Nathan D. Grubaugh, Anna M. Pyle, Akiko Iwasaki
Summary: The antiviral capacity of the minimal RIG-I agonist SLR14 was assessed in mouse models of SARSCoV-2 infection. The study found that SLR14 could prevent viral infection, treat infected mice, and provide cross-variant protection, even in immunodeficient mice.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Biotechnology & Applied Microbiology
Esen Sefik, Benjamin Israelow, Haris Mirza, Jun Zhao, Rihao Qu, Eleanna Kaffe, Eric Song, Stephanie Halene, Eric Meffre, Yuval Kluger, Michel Nussenzweig, Craig B. Wilen, Akiko Iwasaki, Richard A. Flavell
Summary: This study introduces a humanized mouse model of COVID-19 that replicates the immune response and pathological features of the infection, providing a valuable tool for investigating disease mechanisms and treatment options.
NATURE BIOTECHNOLOGY
(2022)
Article
Immunology
Jennifer S. Chen, Ryan D. Chow, Eric Song, Tianyang Mao, Benjamin Israelow, Kathy Kamath, Joel Bozekowski, Winston A. Haynes, Renata B. Filler, Bridget L. Menasche, Jin Wei, Mia Madel Alfajaro, Wenzhi Song, Lei Peng, Lauren Carter, Jason S. Weinstein, Uthaman Gowthaman, Sidi Chen, Joe Craft, John C. Shon, Akiko Iwasaki, Craig B. Wilen, Stephanie C. Eisenbarth
Summary: This study found that both T-FH-dependent and -independent antibodies were induced against SARS-CoV-2 infection, vaccination, and influenza A virus infection. The T-FH-independent antibodies had reduced somatic hypermutation but were still high affinity and capable of neutralizing diverse spike-derived epitopes and variants of concern.
SCIENCE IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Esen Sefik, Rihao Qu, Caroline Junqueira, Eleanna Kaffe, Haris Mirza, Jun Zhao, J. Richard Brewer, Ailin Han, Holly R. Steach, Benjamin Israelow, Holly N. Blackburn, Sofia E. Velazquez, Y. Grace Chen, Stephanie Halene, Akiko Iwasaki, Eric Meffre, Michel Nussenzweig, Judy Lieberman, Craig B. Wilen, Yuval Kluger, Richard A. Flavell
Summary: This study demonstrates that lung-resident human macrophages play a critical role in the development of lung inflammation caused by SARS-CoV-2 infection. Macrophages activate inflammasomes, release inflammatory cytokines, and undergo pyroptosis in response to infection, contributing to the hyperinflammatory state in the lungs. Inhibition of the NLRP3 inflammasome pathway reverses chronic lung pathology, indicating the importance of inflammasome activation in lung inflammation.
Article
Cell Biology
Alexandra Suberi, Molly K. Grun, Tianyang Mao, Benjamin Israelow, Melanie Reschke, Julian Grundler, Laiba Akhtar, Teresa Lee, Kwangsoo Shin, Alexandra S. Piotrowski-Daspit, Robert J. Homer, Akiko Iwasaki, Hee-Won Suh, W. Mark Saltzman
Summary: An inhalable polymer-based vehicle has been developed for the delivery of therapeutic mRNA to the lungs, achieving high transfection efficiency in epithelial and antigen-presenting cells.
SCIENCE TRANSLATIONAL MEDICINE
(2023)