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Viral Immunology Jun 2020
Topics: Allergy and Immunology; Humans; Periodicals as Topic; Research; Virology
PubMed: 32401183
DOI: 10.1089/vim.2020.0078 -
Nature Jan 2024Bacteria encode hundreds of diverse defence systems that protect them from viral infection and inhibit phage propagation. Gabija is one of the most prevalent anti-phage...
Bacteria encode hundreds of diverse defence systems that protect them from viral infection and inhibit phage propagation. Gabija is one of the most prevalent anti-phage defence systems, occurring in more than 15% of all sequenced bacterial and archaeal genomes, but the molecular basis of how Gabija defends cells from viral infection remains poorly understood. Here we use X-ray crystallography and cryo-electron microscopy (cryo-EM) to define how Gabija proteins assemble into a supramolecular complex of around 500 kDa that degrades phage DNA. Gabija protein A (GajA) is a DNA endonuclease that tetramerizes to form the core of the anti-phage defence complex. Two sets of Gabija protein B (GajB) dimers dock at opposite sides of the complex and create a 4:4 GajA-GajB assembly (hereafter, GajAB) that is essential for phage resistance in vivo. We show that a phage-encoded protein, Gabija anti-defence 1 (Gad1), directly binds to the Gabija GajAB complex and inactivates defence. A cryo-EM structure of the virally inhibited state shows that Gad1 forms an octameric web that encases the GajAB complex and inhibits DNA recognition and cleavage. Our results reveal the structural basis of assembly of the Gabija anti-phage defence complex and define a unique mechanism of viral immune evasion.
Topics: Bacteria; Bacterial Proteins; Bacteriophages; Cryoelectron Microscopy; Crystallography, X-Ray; Deoxyribonucleases; DNA, Viral; Immune Evasion; Protein Multimerization
PubMed: 37992757
DOI: 10.1038/s41586-023-06855-2 -
Annual Review of Biochemistry Jun 2020My coworkers and I have used animal viruses and their interaction with host cells to investigate cellular processes difficult to study by other means. This approach has... (Review)
Review
My coworkers and I have used animal viruses and their interaction with host cells to investigate cellular processes difficult to study by other means. This approach has allowed us to branch out in many directions, including membrane protein characterization, endocytosis, secretion, protein folding, quality control, and glycobiology. At the same time, our aim has been to employ cell biological approaches to expand the fundamental understanding of animal viruses and their pathogenic lifestyles. We have studied mechanisms of host cell entry and the uncoating of incoming viruses as well as the synthesis, folding, maturation, and intracellular movement of viral proteins and molecular assemblies. I have had the privilege to work in institutions in four different countries. The early years in Finland (the University of Helsinki) were followed by 6 years in Germany (European Molecular Biology Laboratory), 16 years in the United States (Yale School of Medicine), and 16 years in Switzerland (ETH Zurich).
Topics: Animals; Calnexin; Calreticulin; Cell Line; Endoplasmic Reticulum; Endosomes; Gene Expression Regulation; History, 20th Century; History, 21st Century; Host-Pathogen Interactions; Humans; Influenza A virus; Picornaviridae; Protein Folding; Semliki forest virus; Vesiculovirus; Viral Proteins; Virology; Virus Internalization
PubMed: 32569520
DOI: 10.1146/annurev-biochem-011320-103928 -
Journal of Cardiac Surgery Jun 2020Coronavirus disease (COVID-19) first presented in Wuhan, Hubei province, China in December 2019. Since then, it has rapidly spread across the world, and is now formally... (Review)
Review
Coronavirus disease (COVID-19) first presented in Wuhan, Hubei province, China in December 2019. Since then, it has rapidly spread across the world, and is now formally considered a pandemic. The disease does not discriminate but increasing age and the presence of comorbidities are associated with severe form of the disease and poor outcomes. Although the prevalence of COVID-19 in patients with cardiovascular disease is under-reported, there is evidence that pre-existing cardiac disease can render individuals vulnerable. It is thought that COVID-19 may have both a direct and indirect effect on the cardiovascular system; however, the primary mechanism of underlying cardiovascular involvement is still uncertain. Of particular interest is the role of angiotensin-converting enzyme 2, which is well known for its cardiovascular effects and is also considered to be important in the pathogenesis of COVID-19. With a range of different drug candidates being suggested, effective anti-virals and vaccines are an area of on-going research. While our knowledge of COVID-19 continues to rapidly expand, this review highlights recent advances in our understanding of the interaction between COVID-19 and the cardiovascular system.
Topics: COVID-19; Cardiovascular Diseases; China; Comorbidity; Coronavirus Infections; Female; Global Health; Humans; Male; Pandemics; Pneumonia, Viral; Risk Assessment; Survival Analysis
PubMed: 32369872
DOI: 10.1111/jocs.14596 -
Voprosy Virusologii Nov 2022130 years ago, in 1892, our great compatriot Dmitry Iosifovich Ivanovsky (18641920) discovered a new type of pathogen viruses. Viruses have existed since the birth of...
130 years ago, in 1892, our great compatriot Dmitry Iosifovich Ivanovsky (18641920) discovered a new type of pathogen viruses. Viruses have existed since the birth of life on Earth and for more than three billion years, as the biosphere evolved, they are included in interpopulation interactions with representatives of all kingdoms of life: archaea, bacteria, protozoa, algae, fungi, plants, invertebrates, and vertebrates, including the Homo sapiens (Hominidae, Homininae). Discovery of D.I. Ivanovsky laid the foundation for a new science virology. The rapid development of virology in the 20th century was associated with the fight against emerging and reemerging infections, epidemics (epizootics) and pandemics (panzootics) of which posed a threat to national and global biosecurity (tick-borne and other encephalitis, hemorrhagic fevers, influenza, smallpox, poliomyelitis, HIV, parenteral hepatitis, coronaviral and other infections). Fundamental research on viruses created the basis for the development of effective methods of diagnostics, vaccine prophylaxis, and antiviral drugs. Russian virologists continue to occupy leading positions in some priority areas of modern virology in vaccinology, environmental studies oz zoonotic viruses, studies of viral evolution in various ecosystems, and several other areas. A meaningful combination of theoretical approaches to studying the evolution of viruses with innovative methods for studying their molecular genetic properties and the creation of new generations of vaccines and antiviral drugs on this basis will significantly reduce the consequences of future pandemics or panzootics. The review presents the main stages in the formation and development of virology as a science in Russia with an emphasis on the most significant achievements of soviet and Russian virologists in the fight against viral infectious diseases.
Topics: Animals; Humans; Anniversaries and Special Events; Ecosystem; Influenza, Human; Viruses; Antiviral Agents; Pandemics; Virology
PubMed: 36515283
DOI: 10.36233/0507-4088-140 -
Viruses Dec 2023Norway is situated in a remote and sparsely inhabited part of the world with about 5 [...].
Norway is situated in a remote and sparsely inhabited part of the world with about 5 [...].
Topics: Norway; Virology
PubMed: 38140624
DOI: 10.3390/v15122383 -
Advanced Therapeutics Oct 2021The COVID-19 (coronavirus disease) global pandemic, caused by the spread of the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus, currently has limited... (Review)
Review
The COVID-19 (coronavirus disease) global pandemic, caused by the spread of the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus, currently has limited treatment options which include vaccines, anti-virals, and repurposed therapeutics. With their high specificity, tunability, and biocompatibility, small molecules like peptides are positioned to act as key players in combating SARS-CoV-2, and can be readily modified to match viral mutation rate. A recent expansion of the understanding of the viral structure and entry mechanisms has led to the proliferation of therapeutic viral entry inhibitors. In this comprehensive review, inhibitors of SARS and SARS-CoV-2 are investigated and discussed based on therapeutic design, inhibitory mechanistic approaches, and common targets. Peptide therapeutics are highlighted, which have demonstrated in vitro or in vivo efficacy, discuss advantages of peptide therapeutics, and common strategies in identifying targets for viral inhibition.
PubMed: 34514085
DOI: 10.1002/adtp.202100104 -
Journal of Virology Aug 2021Starting work in a virology research laboratory as a new technician, graduate student, or postdoc can be complex, intimidating, confusing, and stressful. From laboratory...
Starting work in a virology research laboratory as a new technician, graduate student, or postdoc can be complex, intimidating, confusing, and stressful. From laboratory logistics to elemental expectations to scientific specifics, there is much to learn. To help new laboratory members adjust and excel, a series of guidelines for working and thriving in a virology laboratory is presented. While guidelines may be most helpful for new laboratory members, everyone, including principal investigators, is encouraged to use a set of published guidelines as a resource to maximize the time and efforts of all laboratory members. The topics covered here are safety, wellness, balance, teamwork, integrity, reading, research, writing, speaking, and timelines.
Topics: Guidelines as Topic; Humans; Laboratories; Research Design; Research Personnel; Virology
PubMed: 34319158
DOI: 10.1128/JVI.01112-21 -
Cellular Microbiology Feb 2020
Topics: DNA Tumor Viruses; History, 21st Century; Virology
PubMed: 31691475
DOI: 10.1111/cmi.13139 -
Cellular and Molecular Life Sciences :... Dec 2020Heparanase (HPSE) is a multifunctional protein endowed with many non-enzymatic functions and a unique enzymatic activity as an endo-β-D-glucuronidase. The latter allows... (Review)
Review
Heparanase (HPSE) is a multifunctional protein endowed with many non-enzymatic functions and a unique enzymatic activity as an endo-β-D-glucuronidase. The latter allows it to serve as a key modulator of extracellular matrix (ECM) via a well-regulated cleavage of heparan sulfate side chains of proteoglycans at cell surfaces. The cleavage and associated changes at the ECM cause release of multiple signaling molecules with important cellular and pathological functions. New and emerging data suggest that both enzymatic as well as non-enzymatic functions of HPSE are important for health and illnesses including viral infections and virally induced cancers. This review summarizes recent findings on the roles of HPSE in activation, inhibition, or bioavailability of key signaling molecules such as AKT, VEGF, MAPK-ERK, and EGFR, which are known regulators of common viral infections in immune and non-immune cell types. Altogether, our review provides a unique overview of HPSE in cell-survival signaling pathways and how they relate to viral infections.
Topics: Extracellular Matrix; Glucuronidase; Heparitin Sulfate; Humans; Immunity, Cellular; Neoplasms; Signal Transduction; Virus Diseases
PubMed: 32462405
DOI: 10.1007/s00018-020-03559-y