Article
Biochemistry & Molecular Biology
Tong Dai, Lei Zhang, Yu Ran, Meirong Zhang, Bing Yang, Huasong Lu, Shixian Lin, Long Zhang, Fangfang Zhou
Summary: The study reveals that SUMO-specific protease 1 regulates antiviral immunity by deSUMOylating MAVS, which promotes MAVS SUMOylation and aggregation, leading to recruitment and activation of IRF3 for timely antiviral responses. The findings demonstrate the involvement of SUMOylation in MAVS phase separation and reveal a previously unknown mechanism mediated by the SIM in IRF3 for its enrichment in multivalent MAVS droplets.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Microbiology
Jin Dai, Chantal A. Agbemabiese, Ashley N. Griffin, John T. Patton
Summary: This study investigates the role of VP3 and NSP1 proteins in the degradation of MAVS and IRF3 in rotavirus-infected cells. The results demonstrate that VP3 is responsible for the depletion of MAVS and contributes to the suppression of IFN production, supporting the activity of NSP1 as the major interferon antagonist of the virus.
Article
Cell Biology
Jiacheng Wu, Ye Hu, Jiaying Song, Jia Xu, Qian Zhang, Yangyang Chai, Xin Wang, Bingjing Wang, Yong Zhao, Xuetao Cao, Xiaoqing Xu
Summary: Phosphorylation of IRF3 is critical for inducing IFN-I production in antiviral innate response. This study identifies SMYD2 as a negative regulator of IFN-I production by inhibiting IRF3 phosphorylation in macrophages during viral infections. SMYD2 interacts with IRF3 domains and recruits phosphatase PP1α to decrease IRF3 phosphorylation, thereby modulating the antiviral innate response.
CELL DEATH & DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Anne K. Kronborg Hansen, Magdalena Dubik, Joanna Marczynska, Bhavya Ojha, Estanislao Nistal-Villan, Gloria Gonzalez Aseguinolaza, Dina S. Arengoth, Trevor Owens, Reza Khorooshi
Summary: This study investigated the potential therapeutic effect of activating the RIG-I signaling pathway to promote the production of IFN beta within the central nervous system (CNS) and its impact on multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). The results demonstrate that intrathecal administration of AAV-CM resulted in sustained IFN beta expression within the CNS and suppressed the development of EAE. These findings suggest that targeting the downstream signaling pathway of RIG-I represents a promising therapeutic strategy for inflammatory CNS diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Lauren S. Vaughn, Kenneth Frederick, Samuel B. Burnett, Nutan Sharma, D. Cristopher Bragg, Sarah Camargos, Francisco Cardoso, Rekha C. Patel
Summary: This study evaluates the functional role of the most prevalent mutation in DYT-PRKRA patients and finds that it enhances PACT's ability to induce IFN beta. These results provide a new avenue for investigating the underlying molecular mechanisms in DYT-PRKRA.
Article
Immunology
Na Zhang, Han Shi, Miaomiao Yan, Guangliang Liu
Summary: This study reveals that human IFIT5 functions as a negative regulator in the type I IFN signaling pathway by inhibiting the phosphorylation and nuclear translocation of IRF3, therefore impairing the formation of the IRF3-TBK1-IKK epsilon complex and resulting in the degradation of IRF3 and IKK epsilon.
JOURNAL OF IMMUNOLOGY
(2021)
Review
Immunology
Sarah Straub, Natalia G. Sampaio
Summary: Early detection of infection is crucial for our immune system. Mammalian cells have receptors that detect viral RNA, and activation of these receptors can induce immune responses. However, it is now known that these receptors can also be activated without infection, leading to pathological effects. In this review, we discuss recent findings on sterile activation of cytosolic RNA receptors and their roles in disease pathogenesis.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Ziwen Zhou, Xiaolian Cai, Junji Zhu, Zhi Li, Guangqing Yu, Xing Liu, Gang Ouyang, Wuhan Xiao
Summary: OTUD6B gene is induced upon viral infection and functions to suppress cellular antiviral response. It interacts with irf3 and irf7, diminishing their polyubiquitination, thereby impacting the IFN-1 signaling pathway.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Immunology
Anna Kula, Edyta Makuch, Marta Lisowska, Patryk Reniewicz, Tomasz Lipinski, Jakub Siednienko
Summary: Viral infection triggers the innate immune system to produce pro-inflammatory cytokines through pattern recognition receptors. The role of Pellino3 in antibacterial and antiviral response is important but not well understood. This study investigates the involvement of Pellino3 in the RIG-I-dependent signaling pathway during influenza B virus infection. The results suggest that Pellino3 mediates the ubiquitination and degradation of TRAF3, thereby suppressing IRF3 activation and IFNβ production.
Article
Biotechnology & Applied Microbiology
Tao Li, Xiaoshuang Yang, Wei Li, Jiaru Song, Zhuo Li, Xilin Zhu, Xiaopan Wu, Ying Liu
Summary: This study utilized bioinformatics analysis and in vitro and in vivo experiments to confirm the unclear response of chronic hepatitis B patients to interferon-alpha therapy. The research revealed the associations between polymorphisms in MAVS gene and response to IFN-alpha, as well as the mechanism of IFN-alpha downregulating MAVS via RNA editing. The study also highlighted the potential clinical application of MAVS in combination with IFN-alpha for the treatment of HBV infection.
Article
Immunology
Dan-Dan Chen, Jing-Yu Jiang, Long-Feng Lu, Can Zhang, Xiao-Yu Zhou, Zhuo-Cong Li, Yu Zhou, Shun Li
Summary: Zebrafish Ubal negatively regulates IRF3 by inducing K48-linked ub-proteasomal degradation, affecting the IFN immune balance mechanism.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Shufang Jin, Mingyu Li, Hanyue Chang, Ruijie Wang, Zhiyuan Zhang, Jianjun Zhang, Yue He, Hailong Ma
Summary: This study demonstrates that m6A status is downregulated and two demethylases are upregulated in HNSCC. Silencing the m6A demethylase ALKBH5 suppresses tumor progression. ALKBH5 downregulates the m6A modification of DDX58 mRNA, while HNRNPC binds to the m6A sites of DDX58 mRNA to promote its maturation.
Article
Immunology
Chi Zhang, An-Qi Liu, Chu Zhang, Lan-Hao Liu, Jianguo Su, Yong-An Zhang, Jiagang Tu
Summary: This study reveals the virus-host combat mechanism between Cyprinid herpesvirus 3 (CyHV-3) and its host. It shows that CyHV-3 evades host antiviral immunity through its ORF89 protein, while the upregulated host miR-722 targets ORF89 to impede CyHV-3 replication.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Jhao-Yin Lin, Hsing- Huang
Summary: Mesenchymal stem cells (MSCs) have immunomodulatory activity and are effective in treating respiratory viral infections. Infection by IAV PR8 and HCoV229E can increase the expression of IFN-b and IFN-l species in MSCs, and only IFN-b can protect MSCs against viral infection.
MICROBES AND INFECTION
(2023)
Article
Biochemistry & Molecular Biology
Peyman Nahavandi-Parizi, Ashraf Kariminik, Maryam Montazeri
Summary: This study suggests that RIG-1 and IPS-1 play important roles in SARS-CoV-2 infection and their down-regulation may be a strategy employed by the virus to evade immune response.
MOLECULAR BIOLOGY REPORTS
(2023)
Article
Virology
Runrui Dang, Victor G. J. Rodgers, Adolfo Garcia-Sastre, Jiayu Liao
Summary: This study identifies the human SUMOylation pathway as a critical host factor for the IBV viral life cycle. Inhibiting this pathway effectively blocks the replication of IBV, providing a novel strategy for the development of anti-viral therapeutics.
Article
Virology
Mundeep K. Kainth, Joanna S. Fishbein, Teresa Aydillo, Alba Escalera, Rachael Odusanya, Kalliopi Grammatikopoulos, Tiffany Scotto, Christine B. Sethna, Adolfo Garcia-Sastre, Clifford S. Deutschman
Summary: This study investigated antibody and cytokine responses following influenza vaccination in obese children. The results showed that obesity did not alter the efficacy of the vaccine, regardless of metabolic health. However, metabolically unhealthy obese children had decreased IL-13 levels, which may be associated with altered inflammatory response.
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
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)
Review
Virology
Giuseppe Pisanelli, Ugo Pagnini, Giuseppe Iovane, Adolfo Garcia-Sastre
Summary: Paramyxoviruses are negative single-strand RNA viruses that can cause significant diseases in humans and animals. These viruses have evolved different strategies to evade the host's interferon defense mechanism, which is activated upon viral recognition and leads to the production of interferons that reduce viral replication. This article analyzes the current status of the various strategies used by paramyxoviruses to bypass interferon responses.
Article
Microbiology
Aitor Nogales, John Steel, Wen-Chun Liu, Anice C. Lowen, Laura Rodriguez, Kevin Chiem, Andrew Cox, Adolfo Garcia-Sastre, Randy A. Albrecht, Stephen Dewhurst, Luis Martinez-Sobrido
Summary: The study demonstrates that introducing the L319Q substitution in the PB1 protein of the pH1N1 influenza virus can lead to the generation of a less pathogenic and transmissible attenuated virus, providing a basis for the development of a novel LAIV based on a contemporary pH1N1 strain.
MICROBIOLOGY SPECTRUM
(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
Immunology
Sadaf Aslam, Madhusudan Rajendran, Divya Kriti, Andrew Kurland, Jeffrey Johnson, Harm van Bakel, Florian Krammer, Adolfo Garcia-Sastre, Juan Ayllon
Summary: To improve the production yield of seasonal influenza vaccines, we have identified optimal vaccine seed virus backbones for influenza B virus through research and evaluation in embryonated eggs. This study includes 71 strains of influenza B virus from 1940 to the present, representing the known temporal and genetic variability. By assessing the growth profiles and effectiveness of these strains, we selected three strains with the best performance as vaccine seed virus backbones to increase the production yield of influenza B virus seasonal vaccines.
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)
Article
Immunology
Sonia Jangra, Jeffrey J. Landers, Gabriel Laghlali, Raveen Rathnasinghe, Prajakta Warang, Seok-Chan Park, Jessica. J. O'Konek, Gagandeep Singh, Katarzyna W. Janczak, Adolfo Garcia-Sastre, Nandini Arya, Dilara Karadag, Jr James R. Baker, Michael Schotsaert, Pamela T. Wong
Summary: Multiple FDA-approved vaccines provide good protection against severe disease caused by SARS-CoV-2. However, immunity can decline quickly, especially in the elderly, and new viral variants are emerging that can evade the immune response induced by infection or vaccination. Intranasal vaccination is more effective in inducing mucosal immune responses than injectable vaccines, which can improve protection and reduce viral transmission.
Review
Immunology
Vicent Tur-Planells, Adolfo Garcia-Sastre, Sara Cuadrado-Castano, Estanislao Nistal-Villan
Summary: This review provides an overview of non-human-adapted RNA viruses used in cancer therapy and the diverse strategies employed to optimize their therapeutic capabilities. Through this article, we gain insights into the promising advancements in virotherapy and its potential to revolutionize cancer treatment.
