Article
Cell Biology
Linlin Zhu, Hongfeng Yang, Yuelin Chao, Yue Gu, Junxia Zhang, Feng Wang, Wande Yu, Peng Ye, Peng Chu, Xiangquan Kong, Shaoliang Chen
Summary: The study found that LSS exposure led to increased phosphorylation of IKK epsilon, TBK1, and Akt in HUVECs. Akt phosphorylation induced by LSS is positively regulated by IKK epsilon, promoting IRF3 activation and endothelial inflammation. Silencing of TBK1 or inhibition of PI3K and mTORC2 had no effect on LSS-induced Akt phosphorylation.
CELLULAR SIGNALLING
(2021)
Article
Biology
Ya-Ling Chang, Yu-Wen Liao, Min-Hsuan Chen, Sui-Yuan Chang, Yao-Ting Huang, Bing-Ching Ho, Sung-Liang Yu
Summary: The interaction between pathogens and hosts is crucial for understanding infectious diseases. In the case of EV71 infection, host cells trigger IKK epsilon isoform switching to increase interferon production and boost antiviral defense.
COMMUNICATIONS BIOLOGY
(2021)
Article
Immunology
Morgan Brisse, Qinfeng Huang, Mizanur Rahman, Da Di, Yuying Liang, Hinh Ly
Summary: The study demonstrates the crucial roles of MDA5 and RIG-I in controlling Pichinde virus infection in mice. Knockout of MDA5 or both MDA5 and RIG-I results in significantly higher virus titers and lower early IFN-I expression following PICV infection, but a later and heightened adaptive immune response for clearance of the infection is observed.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Yihe Yan, Leting Zheng, Qiang Du, Xiao Cui, Kun Dong, Yarong Guo, David A. Geller
Summary: CHK1 is overexpressed in human HCC tumors compared to non-cancerous liver, and high CHK1 predicts worse prognosis. IFN-gamma suppresses CHK1 in HCC cells through IRF-1, leading to apoptosis. Upregulated IRF-1 induces miR-195 to suppress CHK1 and promote cellular apoptosis in HCC.
BRITISH JOURNAL OF CANCER
(2021)
Article
Fisheries
Can Yang, Juanjuan Shu, Yujia Miao, Xiaoyu Liu, Tianle Zheng, Ruixin Hou, Jun Xiao, Hao Feng
Summary: This study demonstrates that TRIM25 negatively regulates IKK epsilon/IFN signaling by enhancing the ubiquitination of IKK epsilon and inhibiting its phosphorylation. Over-expression of TRIM25 attenuates the activation of IFN signaling and antiviral activity induced by IKK epsilon.
FISH & SHELLFISH IMMUNOLOGY
(2023)
Article
Microbiology
Jun Kang, Mengqian Huang, Jinyu Li, Keke Zhang, Cheng Zhu, Sihua Liu, Zhenwei Zhou, Tao Wang, Zhiyun Wang
Summary: EV-D68 is a globally emerging pathogen causing severe respiratory illnesses mainly in children. The structural protein VP3 of EV-D68 interacts with IRF7 and inhibits its phosphorylation and nuclear translocation, resulting in the repression of IFN production. VP3 also inhibits the ubiquitination of IRF7 induced by TRAF6 through competitive interaction. The control of IRF7 by VP3 may contribute to the subversion of host innate immune responses by EV-D68.
MICROBIOLOGY SPECTRUM
(2023)
Article
Fisheries
Chanyuan Wang, Jun Li, Xiao Yang, Qun Wang, Huijuan Zhong, Yankai Liu, Weiyi Yan, Yunfan He, Zhuoyi Deng, Jun Xiao, Hao Feng
Summary: This study focused on the regulation of IRF3 in black carp by IKKε, showing that bcIRF3 plays a role in antiviral signaling and its interaction with bcIKKε enhances this activity. The nuclear translocation of both proteins was enhanced when co-expressed, although their protein levels decreased mutually.
FISH & SHELLFISH IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Kazi Faizul Azim, Tahera Lasker, Rahima Akter, Mantasha Mahmud Hia, Omar Faruk Bhuiyan, Mahmudul Hasan, Md Nazmul Hossain
Summary: This study aimed to design a highly immunogenic cross-reactive vaccine against Arenaviridae family through reverse vaccinology approach, predicting and screening T-cell and B-cell epitopes. The final constructs showed high conservation and potential broad immunity coverage, indicating the possibility of combating arenaviral infections in the future.
Review
Endocrinology & Metabolism
Artak Labadzhyan, Shlomo Melmed
Summary: Molecular therapeutic targets in growth hormone-secreting adenomas have potential for drug development, including surface receptors recognized by approved drugs and markers for new drug candidates. Current medical therapies control the disease in most patients but the degree of control varies and is related to disease aggressiveness and tumor factors. Understanding the mechanisms behind these molecular markers and their relationship to outcomes holds promise for expanding treatment options and personalized approaches.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Gastroenterology & Hepatology
Chao-Yang Meng, Shiyu Sun, Yong Liang, Hairong Xu, Chao Zhang, Min Zhang, Fu-Sheng Wang, Yang-Xin Fu, Hua Peng
Summary: The study aims to develop an anti-PDL1-IFN alpha fusion protein to overcome immune tolerance induced by chronic hepatitis B virus (HBV) and combine it with a HBV vaccine to achieve functional cure for chronic hepatitis B infection.
Review
Pharmacology & Pharmacy
Fan Feng, Mingying Liu, Lianhong Pan, Jiaqin Wu, Chunli Wang, Li Yang, Wanqian Liu, Wei Xu, Mingxing Lei
Summary: Keloids are a fibroproliferative skin disorder caused by abnormal healing of injured or irritated skin. Mechanical stimulation can lead to excessive fibroblast proliferation, extracellular matrix deposition, and increase of keloid matrix stiffness, while matrix mechanics further activates the fibrotic phenotype. The TGF-beta/Smad signaling pathway, integrin signaling pathway, YAP/TAZ signaling pathway, and calcium ion pathway are involved in keloid formation. Understanding the role of biomechanical factors in keloid formation may facilitate the development of therapeutic interventions.
FRONTIERS IN PHARMACOLOGY
(2022)
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)
Article
Biochemistry & Molecular Biology
Zhen Gan, Jun Cheng, Jing Hou, Liqun Xia, Yishan Lu, Pin Nie
Summary: The study identified a homologous IRF1 gene named Xt-IRF1 in amphibians, which has similar genomic structure and flanking genes, and shows inducible expression under various stimulations.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Yeon-Su Lee, Xiaoyong Bao, Hwi-Ho Lee, Jiyoung Joan Jang, Enkhjin Saruuldalai, Gaeul Park, Wonkyun Ronny Im, Jong-Lyul Park, Seon-Young Kim, Sooyong Shin, Sung Ho Jeon, Sangmin Kang, Hyun-Sung Lee, Ju-Seog Lee, Ke Zhang, Eun Jung Park, In-Hoo Kim, Yong Sun Lee
Summary: The noncoding RNA nc886 acts as a novel suppressor for the IFN-beta signaling and inflammation by inhibiting the activation of IRF3, NF-kappa B, and AP-1 through inhibiting PKR. This leads to decreased expression of IFN-beta and IFN-stimulated genes. Its role is to restrict the IFN-beta signaling from hyperactivation, which may explain the variability of innate immune responses to pathogens based on biological settings.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Virology
Huasong Chang, Hao Wu, Peili Hou, Muhammad Aizaz, Rukun Yang, Aibiao Xiang, Wenjing Qi, Hongbin He, Hongmei Wang
Summary: This study reveals the important role of DLG1 in antiviral innate immunity by promoting the IFN-I response and inhibiting viral replication. DLG1 inhibits the autophagic degradation of IKK epsilon, a crucial adaptor in the innate immune signaling pathway, leading to the attenuation of virus propagation. Mechanistically, DLG1 competitively binds to March2 to prevent the ubiquitination and subsequent degradation of IKK epsilon. Additionally, negative-stranded RNA virus infection decreases DLG1 expression.
JOURNAL OF VIROLOGY
(2023)
Review
Virology
Kin Israel Notarte, Israel Guerrero-Arguero, Jacqueline Veronica Velasco, Abbygail Therese Ver, Maria Helena Santos de Oliveira, Jesus Alfonso Catahay, Md Siddiqur Rahman Khan, Adriel Pastrana, Grzegorz Juszczyk, Jordi B. Torrelles, Giuseppe Lippi, Luis Martinez-Sobrido, Brandon Michael Henry
Summary: This review examines the decline in efficacy of mRNA vaccines for COVID-19 in preventing breakthrough infections due to diminishing humoral immunity over time. The study finds that the peak humoral response is reached 21-28 days after the second dose, after which antibody levels progressively decline at 4-6 months post-vaccination. Regardless of patient-related factors, antibody levels show a decline in both anti-receptor binding domain IgG and anti-spike IgG. The study highlights the need for more efficient vaccination strategies to combat waning immunity.
JOURNAL OF MEDICAL VIROLOGY
(2022)
Article
Microbiology
Maria M. Lorenzo, Aitor Nogales, Kevin Chiem, Rafael Blasco, Luis Martinez-Sobrido
Summary: This study demonstrates that poxviruses can be effectively attenuated by synonymous codon deoptimization, providing a new approach for the development of attenuated vaccines for the treatment of poxvirus infection.
MICROBIOLOGY SPECTRUM
(2022)
Article
Microbiology
Rena A. Mizrahi, Wendy Y. Lin, Ashley Gras, Ariel R. Niedecken, Ellen K. Wagner, Sheila M. Keating, Nikita Ikon, Vishal A. Manickam, Michael A. Asensio, Jackson Leong, Angelica Medina-Cucurella, Emily Benzie, Kyle P. Carter, Yao Chiang, Robert C. Edgar, Renee Leong, Yoong Wearn Lim, Jan Fredrik Simons, Matthew J. Spindler, Kacy Stadtmiller, Nicholas Wayham, Dirk Buscher, Jose Vicente Terencio, Clara Di Germanio, Steven M. Chamow, Charles Olson, Paula A. Pino, Jun-Gyu Park, Amberlee Hicks, Chengjin Ye, Andreu Garcia-Vilanova, Luis Martinez-Sobrido, Jordi B. Torrelles, David S. Johnson, Adam S. Adler
Summary: This study successfully generated a first-in-class recombinant hyperimmune globulin therapeutic against SARS-CoV-2 using microfluidics, flow sorting, and a targeted integration cell line. The drug was manufactured consistently at the clinical scale and offers a new approach to treating infectious diseases by targeting multiple epitopes of the virus.
Article
Biology
Hoda Zarkoob, Anna Allue-Guardia, Yu-Chi Chen, Andreu Garcia-Vilanova, Olive Jung, Steven Coon, Min Jae Song, Jun-Gyu Park, Fatai Oladunni, Jesse Miller, Yen-Ting Tung, Ivan Kosik, David Schultz, James Iben, Tianwei Li, Jiaqi Fu, Forbes D. Porter, Jonathan Yewdell, Luis Martinez-Sobrido, Sara Cherry, Jordi B. Torrelles, Marc Ferrer, Emily M. Lee
Summary: This study investigates the cellular responses to SARS-CoV-2 and influenza A virus infections using human alveolar and tracheobronchial epithelial ALI tissue models, and demonstrates the pharmacological validity of these models as antiviral drug screening assay platforms.
COMMUNICATIONS BIOLOGY
(2022)
Article
Virology
Zachary R. Sia, Kevin Chiem, Wei-Chiao Huang, Amal Seffouh, Amir Teimouri Dereshgi, Tara Hogan, Joaquin Ortega, Bruce A. Davidson, Luis Martinez-Sobrido, Jonathan F. Lovell
Summary: This study demonstrates that an adjuvant-containing nanoliposome antigen display system can effectively induce mucosal immune responses in the respiratory system, leading to the production of local and systemic antibodies, and protect mice from influenza virus challenge.
JOURNAL OF VIROLOGY
(2022)
Article
Virology
Andrei Veleanu, Maximilian A. Kelch, Chengjin Ye, Melanie Flohr, Alexander Wilhelm, Marek Widera, Luis Martinez-Sobrido, Sandra Ciesek, Tuna Toptan
Summary: Some SARS-CoV-2 variants are less susceptible to neutralization by post-vaccine sera and monoclonal antibodies, raising concerns about disease control. This study investigates the impact of spike and non-spike mutations on the virus life cycle. The results suggest that non-spike mutations may play a role in infection kinetics.
Article
Chemistry, Multidisciplinary
Jeonghwan Kim, Antony Jozic, Anindit Mukherjee, Dylan Nelson, Kevin Chiem, Md Siddiqur Rahman Khan, Jordi B. Torrelles, Luis Martinez-Sobrido, Gaurav Sahay
Summary: This study demonstrates that engineered mRNA encoding soluble hACE2 can be delivered to cells using lipid nanoparticles, leading to the production of hsACE2 proteins. The hsACE2 proteins bind to the viral spike protein, preventing viral entry and effectively inhibiting SARS-CoV-2 and its pseudoviruses from infecting host cells. This proof of principle study suggests that mRNA-based nanotherapeutics could be a potential treatment for COVID-19.
Article
Microbiology
Kevin Chiem, Jun-Gyu Park, Desarey Morales Vasquez, Richard K. Plemper, Jordi B. Torrelles, James J. Kobie, Mark R. Walter, Chengjin Ye, Luis Martinez-Sobrido
Summary: Despite the availability of vaccines and antivirals, the SARS-CoV-2 virus continues to cause the COVID-19 pandemic, affecting healthcare institutions worldwide. Previous studies have generated replicable forms of the virus that express fluorescent or luciferase reporter proteins to track viral infection in vitro and/or in vivo. However, the limitations of these approaches have prevented their use in specific assays or studies. In this study, researchers engineered a new form of the virus that expresses both fluorescent (mCherry) and luciferase (Nluc) reporter genes, allowing for better understanding of the virus's behavior in vitro and in vivo. This new model was successfully used to study viral infection and transmission in rodent models using in vivo imaging systems.
MICROBIOLOGY SPECTRUM
(2022)
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
Infectious Diseases
Angela Huttner, Selidji Todagbe Agnandji, Olivier Engler, Jay W. Hooper, Steve Kwilas, Keersten Ricks, Tamara L. Clements, Hulda R. Jonsdottir, Sravya Sowdamini Nakka, Sylvia Rothenberger, Peter Kremsner, Roland Zust, Donata Medaglini, Tom Ottenhoff, Ali M. Harandi, Claire-Anne Siegrist
Summary: This study reports the 5-year persistence and avidity of antibodies produced by the live-attenuated recombinant vesicular stomatitis virus expressing the Zaire Ebolavirus glycoprotein. The findings suggest that antibody titres at 1 year can predict antibody persistence at 5 years. Additionally, while antibody titres remained stable, the duration of live-virus neutralizing antibodies was shorter.
CLINICAL MICROBIOLOGY AND INFECTION
(2023)
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.
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.