Article
Biology
Haifeng C. Xu, Ruifeng Wang, Prashant V. Shinde, Lara Walotka, Anfei Huang, Gereon Poschmann, Jun Huang, Wei Liu, Kai Stuehler, Heiner Schaal, Andreas Bergthaler, Aleksandra A. Pandyra, Cornelia Hardt, Karl S. Lang, Philipp A. Lang
Summary: Using different strains of the lymphocytic choriomeningitis virus (LCMV), Xu, Wang et al. demonstrate that slower viral propagation limits type I interferon (IFN-I) production and viral persistence in mice. This study suggests reduced viral propagation as a mechanism for immune evasion and viral persistence.
COMMUNICATIONS BIOLOGY
(2021)
Article
Immunology
Stephan Isringhausen, YeVin Mun, Larisa Kovtonyuk, Nike J. Kraeutler, Ute Suessbier, Alvaro Gomariz, Gianluca Spaltro, Patrick M. Helbling, Hui Chyn Wong, Takashi Nagasawa, Markus G. Manz, Annette Oxenius, Cesar Nombela-Arrieta
Summary: Chronic viral infections can lead to damage to the bone marrow stromal network, increased inflammatory responses, and impaired function of hematopoietic stem cells. The immune pathology in the bone marrow caused by the virus is mediated by virus-specific, activated CD8 T cells which accumulate in the bone marrow through interferon-dependent mechanisms. Antibody-mediated inhibition of type I and II interferon pathways can prevent degeneration of the bone marrow stroma and protect hematopoietic stem cells from chronic dysfunction.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Microbiology
Sarah van Tol, Birte Kalveram, Philipp A. Ilinykh, Adam Ronk, Kai Huang, Leopoldo Aguilera-Aguirre, Preeti Bharaj, Adam Hage, Colm Atkins, Maria Giraldo, Maki Wakamiya, Maria Gonzalez-Orozco, Abbey N. Warren, Alexander Bukreyev, Alexander N. Freiberg, Ricardo Rajsbaum
Summary: This study identified the important role of VP35 ubiquitination in coordinating viral transcription and assembly. Ubiquitination facilitates optimal viral transcriptional polymerase co-factor function without affecting transcriptional initiation. The loss of a basic charge at position 309 further compromises VP35's function through diminished interaction with the viral matrix protein and type-I interferon antagonism. Overall, ubiquitination and retention of a basic residue at VP35 position 309 are critical for viral transcription and assembly.
Review
Virology
Andrea Modrego, Diego Carlero, Rocio Arranz, Jaime Martin-Benito
Summary: Single-stranded RNA viruses (ssRNAv) pose a major threat to human health due to their biological diversity and adaptability to different hosts. Understanding the mechanisms of viral proliferation is crucial to address the challenges they bring. Ribonucleoproteins (RNPs), which carry out viral transcription and replication, play a key role in these processes. Cryogenic electron microscopy (cryoEM) has revolutionized the study of RNP and nucleocapsid structures in lipid-enveloped ssRNAv, providing valuable insights into their organization and functional implications.
Article
Virology
Maja Santak, Zrinka Matic
Summary: Negative-stranded RNA viruses (NSVs) are important human pathogens that cause severe illnesses. Traditional vaccine design based on viral surface glycoproteins has limitations due to their high variability. Nucleoprotein (NP), a conserved structural protein, is being explored as a promising target for future vaccines. While NP has been shown to elicit effective T-cell immune responses, its role in humoral immunity remains poorly understood.
Article
Microbiology
Lucas J. M. Bruurs, Micha Mueller, Jelle G. Schipper, Huib H. Rabouw, Sanne Boersma, Frank J. M. van Kuppeveld, Marvin E. Tanenbaum
Summary: We investigated the response of human cells to virus infection using real-time imaging and found that heterogeneity in viral replication rates affects the efficiency of antiviral response activation. Additionally, we observed that the strength of the antiviral signaling pathway is linked to qualitatively distinct antiviral responses.
NATURE MICROBIOLOGY
(2023)
Article
Virology
Siddharth Balachandran, Edward S. Mocarski
Summary: ZBP1 is a Z-DNA binding protein that can be activated by Z-RNA in cells infected with orthomyxoviruses and poxviruses, leading to cell death. Z-RNA is sensed in the nucleus of infected cells, but can be sequestered by the viral gene product E3 in the cytoplasm.
CURRENT OPINION IN VIROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Nila Roy Choudhury, Ivan Trus, Gregory Heikel, Magdalena Wolczyk, Jacek Szymanski, Agnieszka Bolembach, Rute Maria Dos Santos Pinto, Nikki Smith, Maryia Trubitsyna, Eleanor Gaunt, Paul Digard, Gracjan Michlewski
Summary: TRIM25 is an E3 ubiquitin ligase that plays a key role in the innate immune response to RNA viruses. It has been shown to bind to RNA, but the exact role of its RNA-binding activity in the immune response is unclear.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Immunology
Michael Basler, Marleen Christ, Heike Goebel, Marcus Groettrup
Summary: The study found that during LCMV infection, IP was upregulated in the liver but not in the spleen in mice lacking the IP subunit LMP7; however, the total proteasome content remained unchanged. Additionally, the expression of standard proteasome subunits was not induced in LMP7-deficient mice during viral infection.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Virology
Mya Myat Ngwe Tun, Kouichi Morita, Takeshi Ishikawa, Shuzo Urata
Summary: This study suggests that the DED/EDh motif present in both arenaviruses and coronaviruses can be a potential drug target. Docking simulation studies showed that compounds ATA and PV6R target the DED/EDh motifs in viral proteins, inhibiting post-entry step of LCMV and SARS-CoV-2 infections. This research provides a new direction for the development of antiviral drugs.
Article
Cell Biology
Adam Hage, Preeti Bharaj, Sarah van Tol, Maria Giraldo, Maria Gonzalez-Orozco, Karl M. Valerdi, Abbey N. Warren, Leopoldo Aguilera-Aguirre, Xuping Xie, Steven G. Widen, Hong M. Moulton, Benhur Lee, Jeffrey R. Johnson, Nevan J. Krogan, Adolfo Garcia-Sastre, Pei-Yong Shi, Alexander N. Freiberg, Ricardo Rajsbaum
Summary: This study identifies the RNA helicase DHX16 as a pattern recognition receptor (PRR) that partners with RIG-I for optimal activation of antiviral immunity requiring unanchored polyubiquitin (poly-Ub).
Article
Biochemical Research Methods
Vineet Gupta, Lorena R. Antunez, Soraia Saleh-Birdjandi, Ozan S. Kumru, Richard Pospisil, Anders Lilja, Gerhard Fuhrmann, Lee Smith, David B. Volkin, Sangeeta B. Joshi
Summary: This study developed a high-throughput infectivity detection method for the viral vector TT1, which showed increased sample throughput and improved assay flexibility compared to traditional methods. This method can be potentially used in vector formulation development and manufacturing processes.
JOURNAL OF VIROLOGICAL METHODS
(2022)
Article
Biochemistry & Molecular Biology
Yinghong Xiao, Peter Lidsky, Yuta Shirogane, Ranen Aviner, Chien-Ting Wu, Weiyi Li, Weihao Zheng, Dale Talbot, Adam Catching, Gilad Doitsh, Weiheng Su, Colby E. Gekko, Arabinda Nayak, Joel D. Ernst, Leonid Brodsky, Elia Brodsky, Elsa Rousseau, Sara Capponi, Simone Bianco, Robert Nakamura, Peter K. Jackson, Judith Frydman, Raul Andino
Summary: Researchers created an antiviral genome eTIP1 by deleting the capsid-coding region of poliovirus, showing significant therapeutic effects against RNA viruses. eTIP1 not only limits virus replication in the nasal cavity but also exerts a non-cell-autonomous antiviral action in the lungs through inducing interferon responses. Moreover, a single dose of eTIP1 not only protects animals from SARS-CoV-2 infection, but also stimulates antibody production for long-term protection.
Review
Medicine, Research & Experimental
Laura Marongiu, Mihai Valache, Fabio A. Facchini, Francesca Granucci
Summary: Dendritic cells play a crucial role in antiviral immunity by sensing viral pathogens and coordinating immune responses. Different subsets of DCs have complementary functions during viral infections, with a particular focus on their interaction with SARS-CoV-2. Although DC-mediated antiviral responses often lead to the production of proinflammatory cytokines and activation of adaptive immunity, the migratory properties of DCs can also contribute to further viral dissemination.
Article
Microbiology
Christian K. Pfaller, Cyril X. George, Charles E. Samuel
Summary: C6 deamination of adenosine to inosine in dsRNA is catalyzed by ADARs enzymes encoded by three genes in mammals. Different ADAR1 proteins, p150 and p110, are produced through alternative promoters and splicing, with ADAR2 being a nuclear enzyme. A-to-I editing occurs in both viral and cellular RNAs, with activity dependent on substrate structure and regulatory RNA-binding proteins.
ANNUAL REVIEW OF VIROLOGY, VOL 8
(2021)
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)
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
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.
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.