Article
Veterinary Sciences
Kun Huang, Haiying Mao, Peilei Ren, Yufei Zhang, Xiaomei Sun, Zhong Zou, Meilin Jin
Summary: Two strains of H5N6 were isolated from chickens and ducks, named XGD and JX. While showing no significant differences in growth kinetics in vitro, JX strain was found to be more virulent in mice. Genetic analysis revealed 13 mutations in six viral proteins of the two strains, highlighting the crucial role of the NS1 protein in enhancing the virulence of JX, specifically through the amino acid 139D.
FRONTIERS IN VETERINARY SCIENCE
(2022)
Article
Infectious Diseases
Sujuan Chen, Xinyu Miao, Dandan Huangfu, Xinyi Zhao, Minxia Zhang, Tao Qin, Daxin Peng, Xiufan Liu
Summary: The addition of five amino acids to the 80-84 positions of the NS1 protein in H5N1 subtype AIVs isolated from mammals enhances pathogenicity by affecting dendritic cells' infection ability and immune responses, resulting in the generation of a cytokine storm.
TRANSBOUNDARY AND EMERGING DISEASES
(2021)
Article
Microbiology
Yen-Chin Liu, Bobo Wing-Yee Mok, Pui Wang, Rei-Lin Kuo, Honglin Chen, Shin-Ru Shih
Summary: A novel mechanistic discovery shows that the host decay factor XRN1 contributes to influenza A virus replication by suppressing the host innate immune response. XRN1 facilitates viral replication through direct association with the viral NS1. The inhibitor pAp can suppress viral growth, suggesting a potential antiviral drug development target.
Article
Virology
Amir Ghorbani, John M. Ngunjiri, Gloria Rendon, Christopher B. Brooke, Scott P. Kenney, Chang-Won Lee
Summary: This study investigated the diversity and complexity of internally deleted genomes in avian influenza viruses, finding that their abundance and diversity depend on viral subculture and purification processes. The occurrence of internally deleted genomes increased in viral clones that exhibited enhanced interferon-inducing capabilities. Computational analyses suggest that these genomes can encode truncated proteins with variable lengths and amino acid composition.
Article
Virology
Bo Zhang, Minxuan Liu, Jiaxin Huang, Qiaoying Zeng, Qiyun Zhu, Shuai Xu, Hualan Chen
Summary: This study demonstrated a novel mechanism by which the NS2 of H1N1 IAV inhibits IRF7-mediated type-I interferon production.
Article
Virology
Elien Vandoorn, Wojciech Stadejek, Anna Parys, Sharon Chepkwony, Koen Chiers, Kristien Van Reeth
Summary: The study found that the H3N2 LAIV strain lvTX98 is only partly attenuated in pigs and is excreted at significant titers after intranasal vaccination. Attenuation and restricted replication of lvTX98 in vivo seemed to be associated with the loss of NS1 functions other than type I IFN antagonism.
JOURNAL OF VIROLOGY
(2022)
Article
Virology
Claudia Blaurock, Angele Breithaupt, David Scheibner, Ola Bagato, Axel Karger, Thomas C. Mettenleiter, Elsayed M. Abdelwhab, Colin R. Parrish
Summary: The highly pathogenic avian influenza viruses H5N8 clade 2.3.4.4A and 2.3.4.4B had devastating impacts on the poultry industry globally, with different pathotypes in ducks. The NS1 protein of these viruses showed preferential evolution towards different lengths, influencing virus replication, transmission, and interferon response in infected chickens and ducks. The NS1 C terminus was found to play a crucial role in the efficient transmission and fitness of H5N8 viruses in birds.
JOURNAL OF VIROLOGY
(2021)
Article
Multidisciplinary Sciences
Valter Bergant, Daniel Schnepf, Niklas de Andrade Kraetzig, Philipp Hubel, Christian Urban, Thomas Engleitner, Ronald Dijkman, Bernhard Ryffel, Katja Steiger, Percy A. A. Knolle, Georg Kochs, Roland Rad, Peter Staeheli, Andreas Pichlmair
Summary: Bergant et al. provide evidence that Influenza A viruses cause alternative polyadenylation of host mRNAs, leading to an attenuated phenotype in mice. This may constitute a common immune evasion mechanism employed by a variety of pathogenic viruses.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Chun-Yang Lin, Meng-Cen Shih, Hung-Chun Chang, Kuan-Jung Lin, Lin-Fang Chen, Sheng-Wen Huang, Mei-Lin Yang, Sheng-Kai Ma, Ai-Li Shiau, Jen-Ren Wang, Kuan-Ru Chen, Pin Ling
Summary: The study revealed that IAV NS1 subverts the RIG-I, TLR3, and TLR7 pathways to type I IFN production by targeting TRAF3 E3 ubiquitin ligase. The conserved FTEE motif in NS1 contains critical E152/E153 residues that are essential for binding TRAF3 and blocking TRAF3 ubiquitination. A recombinant mutant virus with NS1 E152A/E153A mutations induces higher levels of type I IFN and shows attenuated pathogenicity in infected mice.
JOURNAL OF BIOMEDICAL SCIENCE
(2021)
Article
Virology
Amir Ghorbani, Michael C. Abundo, Hana Ji, Kara J. M. Taylor, John M. Ngunjiri, Chang-Won Lee
Summary: Live attenuated influenza vaccines with truncated NS1 have broad protective efficacies through elevated interferon responses. Screening viral subpopulations with enhanced interferon-inducing capacities can guide the design of more effective live vaccines.
JOURNAL OF VIROLOGY
(2021)
Article
Immunology
Wenjiao Wu, Yilu Ye, Yingyuan Zhong, Xiukui Yan, Jianguo Lin, Jianxiang Qiu, Shuwen Liu, Zhixin Fang
Summary: The study found that pterostilbene, a derivative of resveratrol, effectively inhibits influenza A virus infection and induces the production of antiviral interferon type I. Pterostilbene interacts with influenza non-structural 1 (NS1) protein, inhibits RIG-I-mediated ubiquitination degradation, and activates the downstream antiviral pathway, thereby establishing an antiviral state in the cell. These findings suggest that pterostilbene could be a promising option for future development of anti-influenza drugs.
MICROBES AND INFECTION
(2023)
Article
Virology
Yimeng Wang, Jianhong Zhou, Samuel G. Mackintosh, Yuchun Du
Summary: RuvBL2 protein interacts with the NS1 protein of IAV, and decreased levels of RuvBL2 in infected cells lead to apoptosis. The NS1 protein inhibits non-NS1 viral element-induced apoptosis by maintaining RuvBL2 abundance in infected cells.
Article
Virology
Aitor Nogales, Michael Schotsaert, Raveen Rathnasinghe, Marta L. DeDiego, Adolfo Garcia-Sastre, Luis Martinez-Sobrido
Summary: The influenza A virus (IAV) can infect various mammalian and avian species, and studies have developed replication-competent IAV expressing traceable reporter genes to better understand its biology and pathogenesis. These novel approaches provide valuable tools for developing new therapeutic strategies against IAV infections.
Article
Biochemistry & Molecular Biology
Miriam Hanckova, Lucia Mihalikova, Silvia Pastorekova, Tatiana Betakova
Summary: Macrophages in infected tissue are involved in the immune response and can be influenced by hypoxia. In this study, it was found that hypoxia inhibits macrophage proliferation, downregulates the RIG-I-like receptor signalling pathway, and affects the expression of cytokines and pro-inflammatory factors.
Article
Multidisciplinary Sciences
Jingjing Jiang, Yuyu Li, Zeyu Sun, Lan Gong, Xuehui Li, Fan Shi, Jian Yao, Yuting Meng, Xiaohua Meng, Qiong Zhang, Yuchong Wang, Xiaoling Su, Hongyan Diao
Summary: This study discovered that lncNSPL is highly expressed in monocytes of patients infected with influenza A virus (IAV). By blocking the interaction between RIG-I and TRIM25, lncNSPL limits the production of antiviral mediators, promoting IAV replication and immune evasion.
Review
Chemistry, Multidisciplinary
Moustafa T. Mabrouk, Wei-Chiao Huang, Luis Martinez-Sobrido, Jonathan F. Lovell
Summary: The COVID-19 pandemic caused by SARS-CoV-2 has led to millions of deaths globally and emphasized the importance of vaccines. Advanced technologies have enabled rapid development and deployment of COVID-19 vaccines, although access is limited in many developing countries. Different vaccine platforms and nanomaterials have been used to develop COVID-19 vaccines. Continued development of vaccine technologies is crucial for dealing with the ongoing and future pandemics.
ADVANCED MATERIALS
(2022)
Article
Virology
Wenjuan Dong, Heather Mead, Lei Tian, Jun-Gyu Park, Juan Garcia, Sierra Jaramillo, Tasha Barr, Daniel S. Kollath, Vanessa K. Coyne, Nathan E. Stone, Ashley Jones, Jianying Zhang, Aimin Li, Li-Shu Wang, Martha Milanes-Yearsley, Jordi B. Torrelles, Luis Martinez-Sobrido, Paul S. Keim, Bridget Marie Barker, Michael A. Caligiuri, Jianhua Yu
Summary: The K18-hACE2 mouse model provides a comprehensive analysis of SARS-CoV-2 infection and shows that different viral doses lead to varying degrees of organ damage. This model accurately reproduces both severe and non-severe COVID-19 in humans, making it valuable for drug development.
JOURNAL OF VIROLOGY
(2022)
Article
Virology
Ting Y. Wong, Alexander M. Horspool, Brynnan P. Russ, Chengjin Ye, Katherine S. Lee, Michael T. Winters, Justin R. Bevere, Olivia A. Miller, Nathaniel A. Rader, Melissa Cooper, Theodore Kieffer, Julien Sourimant, Alexander L. Greninger, Richard K. Plemper, James Denvir, Holly A. Cyphert, Mariette Barbier, Jordi B. Torrelles, Ivan Martinez, Luis Martinez-Sobrido, F. Heath Damron
Summary: SARS-CoV-2 variants of concern (VoC) have enhanced immune evasion, as demonstrated in this study using passive immunization with human convalescent plasma (HCP). The efficacy of HCP generated to ancestral SARS-CoV-2 was tested against the Alpha, Beta, and Delta VoC in a mouse model. The results show that HCP was unable to control the lethality of these VoC strains, highlighting the need for in vivo models to evaluate emerging strains' immune evasion.
JOURNAL OF VIROLOGY
(2022)
Review
Multidisciplinary Sciences
Julien Sourimant, Carolin M. Lieber, Megha Aggarwal, Robert M. Cox, Josef D. Wolf, Jeong-Joong Yoon, Mart Toots, Chengin Ye, Zachary Sticher, Alexander A. Kolykhalov, Luis Martinez-Sobrido, Gregory R. Bluemling, Michael G. Natchus, George R. Painter, Richard K. Plemper
Summary: This study describes a drug called 4'-fluorouridine (4'-FlU), which has broad-spectrum antiviral effects and potential for the treatment of respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and related RNA virus infections. In vitro and in vivo experiments showed that 4'-FlU inhibited RSV, SARS-CoV-2, and related RNA viruses with high efficacy, making it a promising candidate for broad-spectrum therapeutics against respiratory viruses.
Article
Physiology
Rachel Warren, Andrew M. Dylag, Molly Behan, William Domm, Min Yee, Margot Mayer-Proschel, Luis Martinez-Sobrido, Michael A. O'Reilly
Summary: Children and young adults with mutant forms of the ATM gene, which is involved in DNA damage signaling and mitochondrial homeostasis, suffer from respiratory infections, immune deficiencies, and obstructive airways disease associated with disorganized airway epithelium. A study on mice showed that ATM is required for the regeneration of injured airway epithelium after influenza virus infection. Mice lacking ATM exhibited increased airway resistance and reduced lung compliance during infection, and their lungs developed an abnormal proximal airway epithelium containing cells lacking expression of the immunomodulatory protein Scgb1a1. Restoration of Scgb1a1 expression in the airways required ATM and failure to efficiently restore it may contribute to the respiratory diseases seen in individuals with ataxia telangiectasia.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2022)
Review
Medical Laboratory Technology
Kin Israel Notarte, Abbygail Therese Ver, Jacqueline Veronica Velasco, Adriel Pastrana, Jesus Alfonso Catahay, Gian Luca Salvagno, Eric Peng Huat Yap, Luis Martinez-Sobrido, Jordi B. Torrelles, Giuseppe Lippi, Brandon Michael Henry
Summary: This paper investigates the effects of age, sex, serostatus, and comorbidities on humoral response after mRNA-based Pfizer-BioNTech vaccination. The findings suggest that older individuals, males, seronegative individuals, and those with more comorbidities have a weaker humoral immune response.
CRITICAL REVIEWS IN CLINICAL LABORATORY SCIENCES
(2022)
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
Immunology
Maria M. Lorenzo, Alejandro Marin-Lopez, Kevin Chiem, Luis Jimenez-Cabello, Irfan Ullah, Sergio Utrilla-Trigo, Eva Calvo-Pinilla, Gema Lorenzo, Sandra Moreno, Chengjin Ye, Jun-Gyu Park, Alejandro Matia, Alejandro Brun, Juana M. Sanchez-Puig, Aitor Nogales, Walther Mothes, Pradeep D. Uchil, Priti Kumar, Javier Ortego, Erol Fikrig, Luis Martinez-Sobrido, Rafael Blasco
Summary: The COVID-19 pandemic highlights the need for fast responses and reliable technologies for vaccine development. This study reports on the construction and preclinical testing of a recombinant MVA vaccine, with the MVA-Spf vaccine candidate showing higher levels of antibodies, a stronger T cell response, and a higher degree of protection.
Article
Microbiology
Michael Piepenbrink, Fatai Oladunni, Aitor Nogales, Ahmed M. Khalil, Theresa Fitzgerald, Madhubanti Basu, Christopher Fucile, David J. Topham, Alexander F. Rosenberg, Luis Martinez-Sobrido, James J. Kobie
Summary: Influenza A virus (IAV) infections pose a significant threat to public health due to the variable nature of the virus. This study shows that immunization with a seasonal inactivated influenza vaccine (IIV) can increase the levels of antibodies against H3N2 IAV, a strain known for its genetic drift. These antibodies have broad and potent antiviral activity and can protect against various H3N2 IAV strains. They also persist in the bone marrow, indicating their potential for long-term immunity. These findings contribute to the development of a universal influenza vaccine.
MICROBIOLOGY SPECTRUM
(2023)
Article
Microbiology
Kevin Chiem, Aitor Nogales, Maria Lorenzo, Desarey Morales Vasquez, Yan Xiang, Yogesh K. Gupta, Rafael Blasco, Juan Carlos de la Torre, Luis Martinez-Sobrido
Summary: Despite the eradication of smallpox, some orthopoxviruses, such as monkeypox virus (MPXV), remain important human pathogens. Vaccines for smallpox are effective against MPXV, but limited in access. Current antiviral treatments for MPXV are limited to two FDA-approved drugs. Therefore, there is an urgent need to discover novel antivirals for the treatment of MPXV and other potentially zoonotic orthopoxvirus infections. Here, we found 13 compounds that inhibit both VACV and MPXV, derived from two different libraries of compounds known to inhibit various RNA viruses.
MICROBIOLOGY SPECTRUM
(2023)
Article
Immunology
Luis Martinez-Sobrido, James J. Kobie
Article
Virology
Ahmed M. Khalil, Michael S. Piepenbrink, Ian Markham, Madhubanti Basu, Luis Martinez-Sobrido, James J. Kobie
Summary: IBV contributes significantly to morbidity and mortality, particularly in children, necessitating improvements in vaccines and treatments. A specific hMAb, 1092D4, has been found to have minimal dependence on Fc-effector functions for in vivo antiviral activity.
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.
Review
Immunology
Ahlam Alasiri, Raya Soltane, Akram Hegazy, Ahmed Magdy Khalil, Sara H. Mahmoud, Ahmed A. Khalil, Luis Martinez-Sobrido, Ahmed Mostafa
Summary: Despite being widespread in wild birds and domestic poultry, human infections with highly pathogenic avian influenza H5Nx viruses have been limited since 1996. Few countries use vaccination as a control strategy, while most rely on culling infected flocks. China and Egypt are the major sites where vaccination has been employed, particularly for clade 2.3.4.4b H5N1 viruses. However, improper implementation of control strategies in Egypt has resulted in continuous outbreaks and virus evolution. Comprehensive surveillance in endemic areas is crucial to understand the public health risk of newly emerging immune-evasive or drug-resistant H5Nx variants.