Review
Immunology
Poonam Mudgil
Summary: The antimicrobial lipids in tears provide strong protection to the ocular surface and the cooperative interactions between lipids and proteins can defend against a broad spectrum of pathogens, giving tears self-sterilizing properties.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Review
Immunology
Nighat Perveen, Khalid Muhammad, Sabir Bin Muzaffar, Tean Zaheer, Nayla Munawar, Bojan Gajic, Olivier Andre Sparagano, Uday Kishore, Arve Lee Willingham
Summary: Haematophagous arthropods can carry various pathogens and transmit them to humans and animals, making it important to study their relationship with viruses. Insects have an innate immune system that helps them fight infections. The cellular components of haemolymph, called haemocytes, play a central role in the insect immune system. Mosquitoes and ticks, blood-feeding arthropods, can transmit viral pathogens to their hosts. Despite the arthropod vectors' complex immune response, the viruses can still survive and be transmitted. A multidisciplinary approach is needed to control ectoparasite infestations and prevent vector-borne transmission of viral pathogens to humans and animals.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biology
Adedeji M. Aderounmu, P. Joseph Aruscavage, Bryan Kolaczkowski, Brenda L. Bass, Volker Doetsch
Summary: Antiviral defense in ecdysozoan invertebrates requires Dicer with ATP hydrolysis capability. Human Dicer lacks this ability, suggesting a muted role in antiviral defense. Through ancestral protein reconstruction, it was found that ancient Dicer had ATPase function stimulated by dsRNA. Further analysis showed that dsRNA increased ATP affinity, leading to ATPase activity. Vertebrate Dicer lost ATPase function due to loss of ATP affinity, involving distant motifs important for coupling dsRNA binding to the active conformation.
Article
Multidisciplinary Sciences
Shengzhang Dong, George Dimopoulos
Summary: Ae. aegypti mosquitoes play a crucial role in transmitting important human viral diseases. The disruption of the siRNA pathway by CRISPR/Cas9-mediated Ago2 knockout impairs the mosquitoes' ability to degrade arbovirus RNA, leading to hyper-infection, cell lysis, tissue damage, and ultimately mosquito death.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Po-Yuan Ke
Summary: Autophagy plays a crucial role in antiviral defense by maintaining cellular homeostasis, regulating virus-host interactions, and enhancing innate antiviral immune responses. Additionally, virus-induced autophagy triggers multilayer mechanisms to promote a balance in virus-host cell interactions.
Article
Biochemistry & Molecular Biology
Zhou Yu, Xuelian Li, Mingjin Yang, Jiaying Huang, Qian Fang, Jianjun Jia, Zheng Li, Yan Gu, Taoyong Chen, Xuetao Cao
Summary: TRIM41 plays a crucial role in innate antiviral response by facilitating pathogenic nucleic acids-triggered signaling pathway, interacting with BCL10 and modifying its polyubiquitylation to activate NF-kappa B and TBK1-IRF3 pathways. The deficiency of TRIM41 leads to impaired immune response against viruses, suggesting its potential as a universal E3 ubiquitin ligase in innate antiviral defense mechanism.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2021)
Article
Gastroenterology & Hepatology
Mirco Glitscher, David Heiler Martin, Kathrin Woytinek, Benjamin Schmidt, Denna Tabari, Catharina Scholl, Julia C. Stingl, Evelyn Seelow, Mira Choi, Eberhard Hildt
Summary: The study found that HEV infection leads to decreased cellular cholesterol levels and affects lipid concentrations in patients. Modulating intracellular cholesterol content through drug treatment can impact HEV release, with cholesterol playing a crucial role in this process. This highlights the potential of targeting cholesterol metabolism as an antiviral strategy against HEV.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Allergy
Anastasia Georgountzou, Dimitra Kokkinou, Stella Taka, Paraskevi Maggina, John Lakoumentas, Vassiliki Papaevangelou, Maria Tsolia, Paraskevi Xepapadaki, Evangelos Andreakos, Nikolaos G. Papadopoulos
Summary: The study evaluated the developmental trajectories of the TLR3 and TLR7/8 pathways in healthy and atopic individuals, finding that normal innate immune maturation involves age-related changes in cytokine production. Atopic individuals showed significant differences in certain cytokine synthesis trajectories compared to healthy individuals.
PEDIATRIC ALLERGY AND IMMUNOLOGY
(2021)
Article
Virology
Joe B. Harford, Sang Soo Kim, Kathleen F. Pirollo, Esther H. Chang
Summary: SGT-53 is a novel investigational agent that carries a plasmid vector driving expression of the human TP53 gene. It is currently being tested in phase II trials for advanced pancreatic cancer. Studies have shown that p53, besides being a tumor suppressor, also plays a role in immune responses. Various viruses manipulate p53-dependent pathways to counteract the antiviral activities of the host immune system. Transfection of cells with SGT-53 can produce exogenous active p53 protein, making it a potential therapy for infections including COVID-19.
Article
Fisheries
Shiying Xin, Xing Lv, Linchao Wang, Wei Wei Zheng, Tianjun Xu, Yuena Sun
Summary: With the in-depth study of circRNA, its important role in mammals, such as cell proliferation, apoptosis, invasion, development, and disease state, has been demonstrated. However, the regulatory mechanism of circRNA in lower vertebrates remains unclear. In this study, a new circRNA named circRara was identified and its positive regulatory effect on the antiviral and antibacterial response, cell proliferation, and activity in miiuy croaker was confirmed.
FISH & SHELLFISH IMMUNOLOGY
(2022)
Review
Virology
Wentao Zhang, Yanling Li, Shuyu Xin, Li Yang, Mingjuan Jiang, Yujie Xin, Yiwei Wang, Pengfei Cao, Senmiao Zhang, Yang Yang, Jianhong Lu
Summary: IFIT3 is an important protein induced by interferon, playing a role in antiviral innate immunity and regulating cellular biology. It has the potential to serve as a biomarker for disease diagnosis and therapy.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Microbiology
Madison C. C. Williams, Alexandra E. E. Reker, Shally R. R. Margolis, Jingqiu Liao, Martin Wiedmann, Enrique R. R. Rojas, Alexander J. J. Meeske
Summary: Type VI CRISPR systems use Cas13 to recognize viral mRNA, leading to cell dormancy. This study shows that when combined with DNA-cleaving restriction-modification (RM) systems, type VI CRISPR can help resuscitate cells from dormancy by cleaving the phage genome. The co-occurrence of Cas13 and RM systems enhances the neutralization of phage infections.
NATURE MICROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Peng Gao, Xianwei Ma, Ming Yuan, Yulan Yi, Guoke Liu, Mingyue Wen, Wei Jiang, Ruihua Ji, Lingxi Zhu, Zhen Tang, Qingzhuo Yu, Jing Xu, Rui Yang, Sheng Xia, Mingjin Yang, Jianping Pan, Hongbin Yuan, Huazhang An
Summary: The study highlights the crucial role of Nedd4l in regulating antiviral immunity through promoting ubiquitination of TRAF3, and disruption of Nedd4l impairs the antiviral immune response both in vitro and in vivo.
NATURE COMMUNICATIONS
(2021)
Article
Biochemical Research Methods
Reese A. Martin, Ann T. Tate
Summary: Genes involved in immune defense resist rapidly evolving parasites and pathogens and are highly represented in the immune system. Pleiotropic signaling genes affect multiple phenotypes and may play a role in the evolution of inducible immunity. Pleiotropy is prevalent in immune signaling networks, and it provides an advantage for host fitness during infection.
PLOS COMPUTATIONAL BIOLOGY
(2023)
Review
Immunology
Prashanta Silwal, In Soo Kim, Eun-Kyeong Jo
Summary: Autophagy plays a crucial role in enhancing the immune responses and controlling inflammation against NTM infections, and holds potential as a therapeutic target for combating NTM infections.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Urology & Nephrology
Jan Wysocki, Minghao Ye, Luise Hassler, Ashwani Kumar Gupta, Yuguo Wang, Vlad Nicoleascu, Glenn Randall, Jason A. Wertheim, Daniel Batlle
Summary: A novel ACE2 variant has been developed that can neutralize SARS-CoV-2 infectivity in human kidney organoids, with prolonged duration of action and potential for improved efficacy.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(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
Multidisciplinary Sciences
Jerzy Osipiuk, Saara-Anne Azizi, Steve Dvorkin, Michael Endres, Robert Jedrzejczak, Krysten A. Jones, Soowon Kang, Rahul S. Kathayat, Youngchang Kim, Vladislav G. Lisnyak, Samantha L. Maki, Vlad Nicolaescu, Cooper A. Taylor, Christine Tesar, Yu-An Zhang, Zhiyao Zhou, Glenn Randall, Karolina Michalska, Scott A. Snyder, Bryan C. Dickinson, Andrzej Joachimiak
Summary: The study focused on papain-like protease (PLpro) as a potential target for antivirals against SARS-CoV-2, identifying inhibitors and their interactions with the enzyme. The findings demonstrate the potential for developing high-affinity inhibitors through structure-based drug design efforts targeting PLpro.
NATURE COMMUNICATIONS
(2021)
Article
Biology
Youngchang Kim, Jacek Wower, Natalia Maltseva, Changsoo Chang, Robert Jedrzejczak, Mateusz Wilamowski, Soowon Kang, Vlad Nicolaescu, Glenn Randall, Karolina Michalska, Andrzej Joachimiak
Summary: SARS-CoV-2 Nsp15 is a uridine-specific endoribonuclease that interferes with the innate immune response and is a potential target for therapeutic intervention. Studies have shown that Tipiracil inhibits the activity of Nsp15 by interacting with the uridine binding pocket. This discovery provides new insights for the development of drugs based on uracil scaffold.
COMMUNICATIONS BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Lamiaa El-Shennawy, Andrew D. Hoffmann, Nurmaa Khund Dashzeveg, Kathleen M. McAndrews, Paul J. Mehl, Daphne Cornish, Zihao Yu, Valerie L. Tokars, Vlad Nicolaescu, Anastasia Tomatsidou, Chengsheng Mao, Christopher J. Felicelli, Chia-Feng Tsai, Carolina Ostiguin, Yuzhi Jia, Lin Li, Kevin Furlong, Jan Wysocki, Xin Luo, Carolina F. Ruivo, Daniel Batlle, Thomas J. Hope, Yang Shen, Young Kwang Chae, Hui Zhang, Valerie S. LeBleu, Tujin Shi, Suchitra Swaminathan, Yuan Luo, Dominique Missiakas, Glenn C. Randall, Alexis R. Demonbreun, Michael G. Ison, Raghu Kalluri, Deyu Fang, Huiping Liu
Summary: El-Shennawy et al. found that circulating extracellular vesicles (evACE2) are associated with COVID-19 severity and have a higher efficacy in inhibiting the infection of SARS-CoV-2 variants compared to soluble ACE2. This study is important for the development of therapeutic approaches against current and future coronavirus infections.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Xiaolei Cai, Min Chen, Aleksander Prominski, Yiliang Lin, Nicholas Ankenbruck, Jillian Rosenberg, Mindy Nguyen, Jiuyun Shi, Anastasia Tomatsidou, Glenn Randall, Dominique Missiakas, John Fung, Eugene B. Chang, Pablo Penaloza-MacMaster, Bozhi Tian, Jun Huang
Summary: The study introduces a multifunctional nanoparticle that can capture and inactivate SARS-CoV-2 virus, efficiently blocking viral infection to host cells through surface neutralizing antibodies in vitro. Additionally, the nanoparticle has photothermal function to generate heat for virus inactivation. It significantly outperforms neutralizing antibodies in treating authentic SARS-CoV-2 infection in vivo and provides a flexible platform for potential broad protection against SARS-CoV-2 and its variants.
Article
Multidisciplinary Sciences
Long Chi Nguyen, Dongbo Yang, Vlad Nicolaescu, Thomas J. Best, Haley Gula, Divyasha Saxena, Jon D. Gabbard, Shao-Nong Chen, Takashi Ohtsuki, John Brent Friesen, Nir Drayman, Adil Mohamed, Christopher Dann, Diane Silva, Lydia Robinson-Mailman, Andrea Valdespino, Leticia Stock, Eva Suarez, Krysten A. Jones, Saara-Anne Azizi, Jennifer K. Demarco, William E. Severson, Charles D. Anderson, James Michael Millis, Bryan C. Dickinson, Savas Tay, Scott A. Oakes, Guido F. Pauli, Kenneth E. Palmer, David O. Meltzer, Glenn Randall, Marsha Rich Rosner
Summary: This study found that cannabidiol (CBD) can inhibit the infection of SARS-CoV-2 in cells and mice, potentially making it a preventative agent for early-stage SARS-CoV-2 infection. The study also discovered that CBD inhibits SARS-CoV-2 replication partially by regulating the host cell's endoplasmic reticulum stress response and interferon signaling pathways. However, the current use of non-medical formulations for prevention or treatment is not recommended.
Article
Biochemistry & Molecular Biology
Stanford Schor, Szuyuan Pu, Vlad Nicolaescu, Siavash Azari, Mardo Koivomagi, Marwah Karim, Patricia Cassonnet, Sirle Saul, Gregory Neveu, Andrew Yueh, Caroline Demeret, Jan M. Skotheim, Yves Jacob, Glenn Randall, Shirit Einav
Summary: The study identifies the substrates and pathways regulated by the understudied Numb-associated kinase enzyme BIKE, reveals the mechanism of CLINT1 regulation in DENV infection, and suggests potential roles of BIKE in host immune and stress responses as well as the ubiquitin proteasome system. These findings have implications for cell biology, virology, and host-targeted antiviral design.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Urology & Nephrology
Luise Hassler, Jan Wysocki, Ian Gelarden, Isha Sharma, Anastasia Tomatsidou, Minghao Ye, Haley Gula, Vlad Nicoleascu, Glenn Randall, Sergii Pshenychnyi, Nigar Khurram, Yashpal Kanwar, Dominique Missiakas, Jack Henkin, Anjana Yeldandi, Daniel Batlle
Summary: This study demonstrates the preclinical efficacy of a novel soluble ACE2 protein in a lethal mouse model of SARS-CoV-2 infection, reducing lung and kidney injury.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Article
Multidisciplinary Sciences
Qizhou Lian, Kui Zhang, Zhao Zhang, Fuyu Duan, Liyan Guo, Weiren Luo, Bobo Wing-Yee Mok, Abhimanyu Thakur, Xiaoshan Ke, Pedram Motallebnejad, Vlad Nicolaescu, Jonathan Chen, Chui Yan Ma, Xiaoya Zhou, Shuo Han, Teng Han, Wei Zhang, Adrian Y. Tan, Tuo Zhang, Xing Wang, Dong Xu, Jenny Xiang, Aimin Xu, Can Liao, Fang-Ping Huang, Ya-Wen Chen, Jie Na, Glenn Randall, Hung-fat Tse, Zhiwei Chen, Yin Chen, Huanhuan Joyce Chen
Summary: This study uses a lung and macrophage co-culture system derived from human pluripotent stem cells to investigate the phenotype and gene expression changes in host lung cells and macrophages after SARS-CoV-2 infection. The researchers found differential immune response patterns in distinct macrophage phenotypes, which could contribute to the severity of COVID-19 disease.
NATURE COMMUNICATIONS
(2022)
Article
Biotechnology & Applied Microbiology
Yadi Zhou, Yuan Liu, Shagun Gupta, Mauricio Paramo, Yuan Hou, Chengsheng Mao, Yuan Luo, Julius Judd, Shayne Wierbowski, Marta Bertolotti, Mriganka Nerkar, Lara Jehi, Nir Drayman, Vlad Nicolaescu, Haley Gula, Savas Tay, Glenn Randall, Peihui Wang, John T. Lis, Cedric Feschotte, Serpil C. Erzurum, Feixiong Cheng, Haiyuan Yu
Summary: Studying the interaction between viral and host proteins can help discover therapies for viral infections. In this study, a comprehensive network of interactions between SARS-CoV-2 and human proteins was generated using high-throughput techniques, validating known host factors and identifying new ones. The network showed the highest overlap with differentially expressed genes in COVID-19 patients and revealed an interaction between a viral protein and a human transcription factor. Additionally, network-based screening of FDA-approved or investigational drugs identified several candidates with significant proximity to SARS-CoV-2 host factors, including a drug called carvedilol which showed clinical benefits and antiviral properties.
NATURE BIOTECHNOLOGY
(2022)
Article
Microbiology
Long C. Nguyen, David M. Renner, Diane Silva, Dongbo Yang, Nicholas Parenti, Kaeri M. Medina, Vlad Nicolaescu, Haley Gula, Nir Drayman, Andrea Valdespino, Adil Mohamed, Christopher Dann, Kristin Wannemo, Lydia Robinson-Mailman, Alan Gonzalez, Leticia Stock, Mengrui Cao, Zeyu Qiao, Raymond E. Moellering, Savas Tay, Glenn Randall, Michael F. Beers, Marsha Rich Rosner, Scott A. Oakes, Susan R. Weiss
Summary: This study focused on the inositol-requiring enzyme 1 alpha (IRE1 alpha) pathway, which is part of the host unfolded protein response to virus-induced stress. The researchers found that while MERS-CoV and HCoV-OC43 fully activate the IRE1 alpha kinase and RNase activities, SARS-CoV-2 only partially activates IRE1 alpha, promoting its kinase activity but not RNase activity. Based on changes in IRE1 alpha-dependent gene expression during infection, the study suggests that SARS-CoV-2 inhibits the RNase activation of IRE1 alpha as a strategy to evade detection by the host immune system.
Article
Chemistry, Medicinal
Cole Emanuelson, Nicholas Ankenbruck, Rohan Kumbhare, Meryl Thomas, Colleen Connelly, Yasmine Baktash, Glenn Randall, Alexander Deiters
Summary: A new class of small-molecule miR-122 inhibitors has been discovered, which significantly reduces HCV replication in human liver cells, indicating their potential therapeutic importance.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Microbiology
Chaitanya Kurhade, Soowon Kang, Scott B. Biering, Seungmin Hwang, Glenn Randall
Summary: This study reveals the collaborative action of autophagy and interferon in inhibiting viral replication. It also uncovers the mechanism by which autophagy proteins target viral replication complexes and the role of interferon-inducible GTPases in disrupting these complexes. This research provides a new understanding of the recognition and inhibition of viral replication complexes by the autophagy machinery.
Article
Biology
Luise Hassler, Jan Wysocki, Jared T. Ahrendsen, Minghao Ye, Ian Gelarden, Vlad Nicolaescu, Anastasia Tomatsidou, Haley Gula, Cosimo Cianfarini, Peter Forster, Nigar Khurram, Benjamin D. Singer, Glenn Randall, Dominique Missiakas, Jack Henkin, Daniel Batlle
Summary: Soluble ACE2 protein (ACE2 618-DDC-ABD) administered intranasally improves survival and provides organ protection in SARS-CoV-2-inoculated mice.
LIFE SCIENCE ALLIANCE
(2023)
