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Viruses Nov 2023Oncolytic viruses (OVs) have emerged as one of the most promising cancer immunotherapy agents that selectively target and kill cancer cells while sparing normal cells.... (Review)
Review
Oncolytic viruses (OVs) have emerged as one of the most promising cancer immunotherapy agents that selectively target and kill cancer cells while sparing normal cells. OVs are from diverse families of viruses and can possess either a DNA or an RNA genome. These viruses also have either a natural or engineered tropism for cancer cells. Oncolytic DNA viruses have the additional advantage of a stable genome and multiple-transgene insertion capability without compromising infection or replication. Herpes simplex virus 1 (HSV-1), a member of the oncolytic DNA viruses, has been approved for the treatment of cancers. This success with HSV-1 was achievable by introducing multiple genetic modifications within the virus to enhance cancer selectivity and reduce the toxicity to healthy cells. Here, we review the natural characteristics of and genetically engineered changes in selected DNA viruses that enhance the tumor tropism of these oncolytic viruses.
Topics: Humans; Oncolytic Virotherapy; Neoplasms; Herpesvirus 1, Human; Oncolytic Viruses; Tropism; DNA Viruses
PubMed: 38005938
DOI: 10.3390/v15112262 -
The Lancet. Microbe May 2020
Topics: COVID-19; Humans; Kinetics; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Tropism
PubMed: 32835319
DOI: 10.1016/S2666-5247(20)30008-2 -
Frontiers in Immunology 2021
Topics: Animals; Disease Susceptibility; Host-Parasite Interactions; Humans; Nerve Tissue; Organ Specificity; Parasites; Tropism
PubMed: 34659274
DOI: 10.3389/fimmu.2021.775666 -
Current Opinion in Microbiology Oct 2021Chagas disease is a neglected tropical disease caused by Trypanosoma cruzi parasites. During mammalian infection, T. cruzi alternates between an intracellular stage and... (Review)
Review
Chagas disease is a neglected tropical disease caused by Trypanosoma cruzi parasites. During mammalian infection, T. cruzi alternates between an intracellular stage and extracellular stage. T. cruzi adapts its metabolism to this lifestyle, while also reshaping host metabolic pathways. Such host metabolic adaptations compensate for parasite-induced stress, but may promote parasite survival and proliferation. Recent work has demonstrated that metabolism controls parasite tropism and location of Chagas disease symptoms, and regulates whether infection is mild or severe. Such findings have important translational applications with regards to treatment and diagnostic test development, though further research is needed with regards to in vivo parasite metabolic gene expression, relationship between magnitude of local metabolic perturbation, parasite strain and disease location, and host-parasite-microbiota co-metabolism.
Topics: Animals; Chagas Disease; Metabolic Networks and Pathways; Proteomics; Tropism; Trypanosoma cruzi
PubMed: 34455304
DOI: 10.1016/j.mib.2021.07.015 -
Journal of Biotechnology Jul 2001Both helper dependent expression systems, based on two components, and single genomes constructed by targeted recombination, or by using infectious cDNA clones, have... (Review)
Review
Both helper dependent expression systems, based on two components, and single genomes constructed by targeted recombination, or by using infectious cDNA clones, have been developed. The sequences that regulate transcription have been characterized mainly using helper dependent expression systems and it will now be possible to validate them using single genomes. The genome of coronaviruses has been engineered by modification of the infectious cDNA leading to an efficient (>20 microg ml(-1)) and stable (>20 passages) expression of the foreign gene. The possibility of engineering the tissue and species tropism to target expression to different organs and animal species, including humans, increases the potential of coronaviruses as vectors. Thus, coronaviruses are promising virus vectors for vaccine development and, possibly, for gene therapy.
Topics: Coronavirus; Gene Expression Regulation, Viral; Genetic Therapy; Genetic Vectors; Genome, Viral; Humans; Transcription, Genetic; Tropism; Vaccines
PubMed: 11434966
DOI: 10.1016/s0168-1656(01)00281-4 -
The Journal of Biological Chemistry Feb 2020Research in the last decade has uncovered many new paramyxoviruses, airborne agents that cause epidemic diseases in animals including humans. Most paramyxoviruses enter... (Review)
Review
Research in the last decade has uncovered many new paramyxoviruses, airborne agents that cause epidemic diseases in animals including humans. Most paramyxoviruses enter epithelial cells of the airway using sialic acid as a receptor and cause only mild disease. However, others cross the epithelial barrier and cause more severe disease. For some of these viruses, the host receptors have been identified, and the mechanisms of cell entry have been elucidated. The tetrameric attachment proteins of paramyxoviruses have vastly different binding affinities for their cognate receptors, which they contact through different binding surfaces. Nevertheless, all input signals are converted to the same output: conformational changes that trigger refolding of trimeric fusion proteins and membrane fusion. Experiments with selectively receptor-blinded viruses inoculated into their natural hosts have provided insights into tropism, identifying the cells and tissues that support growth and revealing the mechanisms of pathogenesis. These analyses also shed light on diabolically elegant mechanisms used by morbilliviruses, including the measles virus, to promote massive amplification within the host, followed by efficient aerosolization and rapid spread through host populations. In another paradigm of receptor-facilitated severe disease, henipaviruses, including Nipah and Hendra viruses, use different members of one protein family to cause zoonoses. Specific properties of different paramyxoviruses, like neurotoxicity and immunosuppression, are now understood in the light of receptor specificity. We propose that research on the specific receptors for several newly identified members of the family that may not bind sialic acid is needed to anticipate their zoonotic potential and to generate effective vaccines and antiviral compounds.
Topics: Animals; Humans; Membrane Fusion; Paramyxoviridae; Receptors, Virus; Tropism; Virus Attachment; Virus Internalization; Zoonoses
PubMed: 31949044
DOI: 10.1074/jbc.REV119.009961 -
World Journal of Gastroenterology Dec 2022The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hepatic involvement is common in... (Review)
Review
The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hepatic involvement is common in SARS-CoV-2-infected individuals. It is currently accepted that the direct and indirect hepatic effects of SARS-CoV-2 infection play a significant role in COVID-19. In individuals with pre-existing infectious and non-infectious liver disease, who are at a remarkably higher risk of developing severe COVID-19 and death, this pathology is most medically relevant. This review emphasizes the current pathways regarded as contributing to the gastrointestinal and hepatic ailments linked to COVID-19-infected patients due to an imbalanced interaction among the liver, systemic inflammation, disrupted coagulation, and the lung.
Topics: Humans; SARS-CoV-2; COVID-19; Liver; Inflammation; Tropism
PubMed: 36632318
DOI: 10.3748/wjg.v28.i48.6875 -
Current Biology : CB Sep 2017Plants are sessile organisms rooted in one place. The soil resources that plants require are often distributed in a highly heterogeneous pattern. To aid foraging, plants... (Review)
Review
Plants are sessile organisms rooted in one place. The soil resources that plants require are often distributed in a highly heterogeneous pattern. To aid foraging, plants have evolved roots whose growth and development are highly responsive to soil signals. As a result, 3D root architecture is shaped by myriad environmental signals to ensure resource capture is optimised and unfavourable environments are avoided. The first signals sensed by newly germinating seeds - gravity and light - direct root growth into the soil to aid seedling establishment. Heterogeneous soil resources, such as water, nitrogen and phosphate, also act as signals that shape 3D root growth to optimise uptake. Root architecture is also modified through biotic interactions that include soil fungi and neighbouring plants. This developmental plasticity results in a 'custom-made' 3D root system that is best adapted to forage for resources in each soil environment that a plant colonises.
Topics: Gravitropism; Phototropism; Plant Roots; Seedlings; Soil
PubMed: 28898665
DOI: 10.1016/j.cub.2017.06.043 -
Nature Reviews. Immunology Sep 2009The specificity of a given virus for a cell type, tissue or species - collectively known as viral tropism - is an important factor in determining the outcome of viral... (Review)
Review
The specificity of a given virus for a cell type, tissue or species - collectively known as viral tropism - is an important factor in determining the outcome of viral infection in any particular host. Owing to the increased prevalence of zoonotic infections and the threat of emerging and re-emerging pathogens, gaining a better understanding of the factors that determine viral tropism has become particularly important. In this Review, we summarize our current understanding of the central role of antiviral and pro-inflammatory cytokines, particularly the interferons and tumour necrosis factor, in dictating viral tropism and how these cytokine pathways can be exploited therapeutically for cancer treatment and to better counter future threats from emerging zoonotic pathogens.
Topics: Animals; Cytokines; Humans; Interferons; Oncolytic Virotherapy; Tropism; Tumor Necrosis Factor-alpha; Viruses
PubMed: 19696766
DOI: 10.1038/nri2623 -
Nature Communications Nov 2023The introduction of more effective and selective mRNA delivery systems is required for the advancement of many emerging biomedical technologies including the development...
The introduction of more effective and selective mRNA delivery systems is required for the advancement of many emerging biomedical technologies including the development of prophylactic and therapeutic vaccines, immunotherapies for cancer and strategies for genome editing. While polymers and oligomers have served as promising mRNA delivery systems, their efficacy in hard-to-transfect cells such as primary T lymphocytes is often limited as is their cell and organ tropism. To address these problems, considerable attention has been placed on structural screening of various lipid and cation components of mRNA delivery systems. Here, we disclose a class of charge-altering releasable transporters (CARTs) that differ from previous CARTs based on their beta-amido carbonate backbone (bAC) and side chain spacing. These bAC-CARTs exhibit enhanced mRNA transfection in primary T lymphocytes in vitro and enhanced protein expression in vivo with highly selective spleen tropism, supporting their broader therapeutic use as effective polyanionic delivery systems.
Topics: RNA, Messenger; Transfection; T-Lymphocytes; Gene Editing; Tropism
PubMed: 37914693
DOI: 10.1038/s41467-023-42672-x