Review
Immunology
Koji Onomoto, Kazuhide Onoguchi, Mitsutoshi Yoneyama
Summary: RLRs are RNA sensor molecules that play essential roles in innate antiviral immunity by inducing downstream signaling via interactions with various host and viral factors. The signaling mediated by RLRs is regulated by interactions with endogenous RNAs and host proteins, and deregulation can lead to autoimmune and autoinflammatory disorders.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Katarzyna Wicherska-Pawlowska, Tomasz Wrobel, Justyna Rybka
Summary: The innate immune system recognizes pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) through pattern recognition receptors (PRRs), activating immune cells and initiating inflammatory and immune responses. This system also plays a role in cancer immunosurveillance, with potential for natural and synthetic agonists of PRRs to be used as adjuvants in cancer immunotherapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Microbiology
Zhihua Ren, Yueru Yu, Chaoxi Chen, Dingyong Yang, Ting Ding, Ling Zhu, Junliang Deng, Zhiwen Xu
Summary: Long noncoding RNAs can regulate viral replication by modulating glycolysis and antiviral immune responses. The mitochondrial antiviral signaling protein (MAVS) plays a crucial role in bridging the gap between antiviral immunity and glycolysis, while lactate production can impair the antiviral immune response. LncRNAs also regulate antiviral innate immunity by interfering with RIG-I and downstream signaling pathways.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Immunology
Raphael Jami, Emilie Merour, Annie Lamoureux, Julie Bernard, Jean K. Millet, Stephane Biacchesi
Summary: Interferons play a crucial role in fighting viral infections in the early stages, with their synthesis tightly regulated. The RIG-I-like receptor signaling cascade is a major pathway leading to interferon production. Recent studies suggest that fish can be attractive and powerful models for studying the regulation and evolution of the RIG-I pathway.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Thabiso Miya, Michelle J. Groome, Debra de Assis Rosa
Summary: Research indicates that genetic variations in TLR genes may affect IgA antibody production and seroconversion after Rotarix vaccination in Black South African infants. The efficacy of the vaccine is influenced by factors such as birthweight and pre-vaccine antibody titres.
Article
Virology
Daniel D. T. Andrews, Marli Vlok, Dorssa Akbari Bani, Brenna N. Hay, Yasir Mohamud, Leonard J. Foster, Honglin Luo, Christopher M. Overall, Eric Jan
Summary: Host antiviral factors use the retinoic acid-inducible gene I (RIG-I)-like receptor pathway to sense virus infection and trigger the production of interferons, which establish an antiviral state. The chaperone protein 14-3-3 & epsilon; plays a key role in this pathway by facilitating the delivery of the viral sensor protein RIG-I to the mitochondria. However, the enteroviral 3C protease cleaves 14-3-3 & epsilon; during infection, disrupting its function and promoting virus infection. This study reveals a novel viral strategy that evades the host antiviral response.
JOURNAL OF VIROLOGY
(2023)
Article
Critical Care Medicine
James Verbsky
Summary: A protective immune response to viruses involves the recognition of viral molecular patterns by cells, leading to an immune response and the production of interferon proteins to limit viral replication.
CRITICAL CARE CLINICS
(2022)
Article
Chemistry, Medicinal
Ming-Hsiu Yang, Jamie L. Russell, Yuto Mifune, Ying Wang, Hexin Shi, Eva Marie Y. Moresco, Daniel J. Siegwart, Bruce Beutler, Dale L. Boger
Summary: Diprovocims are a new class of TLR agonists that act through the TLR1/TLR2 mechanism, exhibit structure-activity relationships, and have in vivo adjuvant activity. They have potent agonist activity towards human TLR1/TLR2 and can be functionalized without impacting this activity. Improvement in potency and efficacy in the murine system has also been achieved.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Immunology
Huanan Li, Yang Guo, Wenbao Qi, Ming Liao
Summary: This review provides an overview of the role of m(6)A RNA modification in viral replication and immune escape, and discusses the potential of m(6)A as a novel antiviral target.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Virology
Sarah van Tol, Adam Hage, Ricardo Rajsbaum, Alexander N. Freiberg
Summary: The expression of TRIM40 in bat cells during Nipah virus infection helps control the infection by reducing viral titers, while its expression is suppressed in human cells. These findings suggest that bats may achieve tolerance to viral infections by regulating the expression of TRIM40.
Article
Virology
Jiaying Yu, Haitao Shi, Ke Song, Yuxin Yang, Xinmiao Li, Luyuan Peng, Bendong Fu, Pengfei Yi
Summary: Porcine reproductive and respiratory syndrome (PRRS) is a major disease in the swine industry, and its pathogen PRRSV has immunosuppressive properties. This study investigated the modulatory effect of naringenin on the suppressed innate immune response after PRRSV infection and found that it improved the expression of antiviral cytokines and activated the RIG-I-MAVS immune signaling pathway. These findings suggest that naringenin may have potential as a drug against immunosuppressive viral infections.
Article
Medicine, General & Internal
Killian E. Vlaming, Kelly van Wijnbergen, Tanja M. Kaptein, Monique Nijhuis, Neeltje J. Kootstra, Godelieve J. de Bree, Teunis B. Geijtenbeek
Summary: This study investigated the effects of co-stimulation of TLR agonists with RLR agonists on antiviral immunity. The results showed that co-stimulation of TLR8 agonists and RLR agonist polyI: C significantly increased the production of IL-12p70 and type I interferon (IFN), suggesting that the crosstalk between TLRs and RLRs leads to strong antiviral immune responses.
FRONTIERS IN MEDICINE
(2023)
Review
Medicine, Research & Experimental
Manish Muhuri, Yukiko Maeda, Hong Ma, Sanjay Ram, Katherine A. Fitzgerald, W. L. Phillip, Guangping Gao
Summary: Research has shown that host immune responses against rAAVs have hindered the progress of gene therapy. Both the innate and adaptive arms of the immune system play a role in this response.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Biochemistry & Molecular Biology
Joanne Wayne, Teresa Brooks, Alexandra Landras, Andrew J. Massey
Summary: Activating stimulator of interferon genes to turn immunologically refractive cold tumor hot is an exciting therapeutic approach to increase the clinical responsiveness of some human cancers to immune checkpoint inhibitors. However, there are challenges in combining Chk1 or Wee1 inhibitors with immune checkpoint inhibitors that need further investigation.
Editorial Material
Biochemistry & Molecular Biology
Ingo Schmitz, Sabrina Muehlen
Summary: NOD1 is an intracellular immune receptor that recognizes bacteria and activates immune responses. In addition to its role in pathogen recognition, NOD1 is also involved in cancer progression. Hezinger et al. discovered a non-canonical role of NOD1 in cell migration and identified HAX-1 as a novel interaction partner.
Article
Immunology
J. Nakawesi, S. This, J. Hutter, M. Boucard-Jourdin, V. Barateau, K. Getachew Muleta, L. J. Gooday, K. Fog Thomsen, A. Garcias Lopez, I. Ulmert, D. Poncet, B. Malissen, H. Greenberg, O. Thaunat, T. Defrance, H. Paidassi, K. Lahl
Summary: The study reveals that BATF3-dependent cDC1 cells are critical for the induction of rotavirus-specific IgA responses in the mesenteric lymph nodes, through the selective expression of the TGF beta-activating integrin alpha v beta 8. In contrast, cDC2 cells are dispensable for this process, suggesting that the capacity of DC subsets to induce intestinal IgA responses is context-dependent.
MUCOSAL IMMUNOLOGY
(2021)
Article
Immunology
Joseph Eiden, Bram Volckaert, Oleg Rudenko, Roger Aitchison, Renee Herber, Robert Belshe, Harry Greenberg, Kathleen Coelingh, David Marshall, Yoshihiro Kawaoka, Gabriele Neumann, Pamuk Bilsel
Summary: This study demonstrates that vaccine-induced neutralizing antibodies can protect against infection and illness from different virus strains. It is the first evidence of vaccine-induced protection against a highly drifted H3N2 challenge virus.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Virology
Siyuan Ding, Harry B. Greenberg
Summary: In the past four years, there has been a surge in research and publications in the rotavirus (RV) field using fully plasmid-based RV reverse genetics systems and modifications. However, it has been found that many other animal and human RV strains, reporter viruses, and clinical isolates have been difficult or impossible to rescue using the original system. Further modifications to the reverse genetics system have enabled the rescue of additional RV strains, pointing towards the potential for future enhancements in efficiency and design of next-generation RV vaccine candidates and viral vectors.
Article
Biochemistry & Molecular Biology
Yanhua Song, Gaopeng Hou, Jonathan Diep, Yaw Shin Ooi, Natalia S. Akopyants, Stephen M. Beverley, Jan E. Carette, Harry B. Greenberg, Siyuan Ding
Summary: ING3 plays a crucial role in silencing ERVs by establishing EZH2-mediated H3K27 trimethylation modification, leading to the induction of MDA5-MAVS-interferon signaling and functional inhibition of several virus infections. Loss of ING3 results in decreased H3K27 trimethylation enrichment at ERVs, demonstrating an important new function of ING3 in ERV silencing and contributing to innate immune regulation in somatic cells.
NUCLEIC ACIDS RESEARCH
(2021)
Meeting Abstract
Biochemistry & Molecular Biology
Kristen Engevik, Takahiro Kawagishi, Harry Greenberg, Joseph Hyser
Article
Virology
Ciara T. Hu, Karina Diaz, Linda C. Yang, Anjali Sharma, Harry B. Greenberg, Jason G. Smith
Summary: This study highlights the potential role of enteric alpha-defensins in the evolution and tropism of rotaviruses, with species-specific activities observed. The VP4 protein of rotavirus is identified as a determinant of alpha-defensin sensitivity. These findings provide insights into the mechanism of defensin neutralization and emphasize the importance of studying a broader range of rotaviruses with different VP4 genotypes.
JOURNAL OF VIROLOGY
(2022)
Article
Virology
Gerson I. Caraballo, Romel Rosales, Mercedes Viettri, Juan Manuel Castillo, Raymundo Cruz, Siyuan Ding, Harry B. Greenberg, Juan E. Ludert
Summary: Dengue is the most important mosquito-borne viral disease to humans. Dengue virus NS1 is a multifunctional protein essential for replication and modulation of innate immunity. The protein interactome of DENV NS1 in mosquito cells was investigated, revealing interactions with various mosquito protein targets. This study provides novel insights into the functions of NS1 and its role in promoting viral replication, as well as identifying new protein pathways involved in mosquito cells.
JOURNAL OF VIROLOGY
(2022)
Article
Virology
Simon Jenni, Zongli Li, Yuhuan Wang, Theresa Bessey, Eric N. Salgado, Aaron G. Schmidt, Harry B. Greenberg, Baoming Jiang, Stephen C. Harrison
Summary: Rotavirus live-attenuated vaccines generate broadly heterotypic protection and B-cells isolated from adults encode antibodies that are broadly protective in mice. Understanding the structural and mechanistic basis of this broad protection can help in addressing the limitations of vaccine efficacy in developing countries.
JOURNAL OF VIROLOGY
(2022)
Article
Virology
Liliana Sanchez-Tacuba, Takahiro Kawagishi, Ningguo Feng, Baoming Jiang, Siyuan Ding, Harry B. Greenberg
Summary: The basis for rotavirus host range restriction is likely multigenic, with VP3, VP4, NSP1, NSP2, NSP3, and NSP4 genes associated with host range restriction. VP4, the cell attachment protein, is linked to host range restriction, but its exact role is still unclear. The genetic origin of VP4 partially modulates host range restriction in suckling mice, with both VP8* and VP5* domains contributing independently to pathogenesis and transmission.
JOURNAL OF VIROLOGY
(2022)
Article
Immunology
Yinxing Zhu, Liliana Sanchez-Tacuba, Gaopeng Hou, Takahiro Kawagishi, Ningguo Feng, Harry B. Greenberg, Siyuan Ding
Summary: In this study, a recombinant murine-like rotavirus (RV) encoding a Nano-Luciferase reporter was generated and used to track the replication and transmission dynamics of the virus in vivo. The NLuc-expressing RV showed replication competence in cell culture and virulence in neonatal mice. Noninvasive imaging revealed that RV replication peaked at days 2 to 5 post infection, and transmission to uninoculated littermates occurred as early as 3 days post infection. The study provides a valuable tool for studying tissue tropism and factors regulating RV replication and spread.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Joseph Eiden, Carlos Fierro, Howard Schwartz, Mark Adams, Kimberly J. Ellis, Roger Aitchison, Renee Herber, Yasuko Hatta, David Marshall, Michael J. Moser, Robert Belshe, Harry Greenberg, Kathleen Coelingh, Yoshihiro Kawaoka, Gabriele Neumann, Pamuk Bilsel
Summary: High dose of intranasal single replication M2SR influenza vaccine enhances mucosal and serum antibodies against drifted H3N2 influenza viruses. This vaccine demonstrates a potential more effective protection strategy against multiple circulating influenza strains and influenza variants.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Multidisciplinary Sciences
Takahiro Kawagishi, Liliana Sanchez-Tacuba, Ningguo Feng, Veronica P. Costantini, Ming Tan, Xi Jiang, Kim Y. Green, Jan Vinje, Siyuan Ding, Harry B. Greenberg
Summary: Rotaviruses (RVs) primarily replicate in the small intestine and cause severe diarrheal disease. Rhesus rotavirus (RRV) can be used as a vaccine and has been extensively studied in mice. Recombinant RVs expressing foreign proteins have not been tested as vaccine vectors yet. This study showed that recombinant RRVs expressing human norovirus proteins can induce an immune response in mice, suggesting the potential of using RV as a vaccine vector against gastrointestinal pathogens.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Virology
Ciara T. Hu, Karina Diaz, Linda C. Yang, Anjali Sharma, Harry B. Greenberg, Jason G. Smith
Summary: The study investigates the role of alpha-defensins in the replication and transmission of fecal-oral pathogens. The activity of alpha-defensins varies between species and can affect microbial evolution, tissue tropism, species tropism, and zoonotic potential. The research highlights the resistance and sensitivity of rotaviruses to host enteric alpha-defensins and identifies the viral protein VP4 as a determinant of alpha-defensin sensitivity.
JOURNAL OF VIROLOGY
(2023)
Meeting Abstract
Pathology
Kristen Engevik, Takahiro Kawagishi, John Thomas Gebert, Francesca Scribano, Jacob Perry, Harry Greenberg, Joseph Hyser
AMERICAN JOURNAL OF PATHOLOGY
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Romain Ballet, Martin Brennan, Carolin Brandl, Ningguo Feng, Jeremy Berri, Julian Cheng, Borja Ocon, Amin Alborzian Deh Sheikh, Alex Marki, Yuhan Bi, Clare Abram, Clifford Lowell