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BMC Immunology Dec 2018Oncolytic viruses have been proposed to be employed as a potential treatment of cancer. Well targeted, they will serve the purpose of cracking tumor cells without... (Review)
Review
BACKGROUND
Oncolytic viruses have been proposed to be employed as a potential treatment of cancer. Well targeted, they will serve the purpose of cracking tumor cells without causing damage to normal cells. In this category of oncolytic viral drugs human pathogens herpes simplex virus (HSV) is especially suitable for the cause. Although most viral infection causes antiviral reaction in the host, HSV has multiple mechanisms to evade those responses. Powerful anti-tumor effect can thus be achieved via genetic manipulation of the HSV genes involved in this evading mechanism, namely deletions or mutations that adapt its function towards a tumor microenvironment. Currently, oncolytic HSV (oHSV) is widely use in clinical; moreover, there's hope that its curative effect will be further enhanced through the combination of oHSV with both traditional and emerging therapeutics.
RESULTS
In this review, we provide a summary of the HSV host antiviral response evasion mechanism, HSV expresses immune evasion genes such as ICP34.5, ICP0, Us3, which are involved in inducing and activating host responses, so that the virus can evade the immune system and establish effective long-term latent infection; we outlined details of the oHSV strains generated by removing genes critical to viral replication such as ICP34.5, ICP0, and inserting therapeutic genes such as LacZ, granulocyte macrophage colony-stimulating factor (GM-CSF); security and limitation of some oHSV such G207, 1716, OncoVEX, NV1020, HF10, G47 in clinical application; and the achievements of oHSV combined with immunotherapy and chemotherapy.
CONCLUSION
We reviewed the immunotherapy mechanism of the oHSV and provided a series of cases. We also pointed out that an in-depth study of the application of oHSV in cancer treatment will potentially benefits cancer patients more.
Topics: Humans; Immunotherapy; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Simplexvirus
PubMed: 30563466
DOI: 10.1186/s12865-018-0281-9 -
Current Opinion in Virology Aug 2013While viral latency remains one of the biggest challenges for successful antiviral therapy, it has also inspired mathematical modelers to develop dynamical system... (Review)
Review
While viral latency remains one of the biggest challenges for successful antiviral therapy, it has also inspired mathematical modelers to develop dynamical system approaches with the aim of predicting the impact of drug efficacy on disease progression and the persistence of latent viral reservoirs. In this review we present several differential equation models and assess their relative success in giving advice to the working clinician and their predictive power for inferring long term viral eradication from short term abatement. Many models predict that there is a considerable likelihood of viral rebound due to continuous reseeding of latent reservoirs. Most mathematical models of HIV latency suffer from being reductionist by ignoring the growing variety of different cell types harboring latent virus, the considerable intercellular delay involved in reactivation, and host-related epigenetic modifications which may alter considerably the dynamical system of immune cell populations.
Topics: Animals; HIV Infections; HIV-1; Herpes Simplex; Humans; Models, Theoretical; Simplexvirus; Virus Latency
PubMed: 23896280
DOI: 10.1016/j.coviro.2013.06.015 -
International Journal of Molecular... Nov 2020Oncolytic viruses are smart therapeutics against cancer due to their potential to replicate and produce the needed therapeutic dose in the tumor, and to their ability to... (Review)
Review
Oncolytic viruses are smart therapeutics against cancer due to their potential to replicate and produce the needed therapeutic dose in the tumor, and to their ability to self-exhaust upon tumor clearance. Oncolytic virotherapy strategies based on the herpes simplex virus are reaching their thirties, and a wide variety of approaches has been envisioned and tested in many different models, and on a range of tumor targets. This huge effort has culminated in the primacy of an oncolytic HSV (oHSV) being the first oncolytic virus to be approved by the FDA and EMA for clinical use, for the treatment of advanced melanoma. The path has just been opened; many more cancer types with poor prognosis await effective and innovative therapies, and oHSVs could provide a promising solution, especially as combination therapies and immunovirotherapies. In this review, we analyze the most recent advances in this field, and try to envision the future ahead of oHSVs.
Topics: Combined Modality Therapy; Herpesvirus 1, Human; Humans; Oncolytic Virotherapy; Oncolytic Viruses; Simplexvirus
PubMed: 33167582
DOI: 10.3390/ijms21218310 -
Annual Review of Microbiology 2014The purpose of this review is to explore recombination strategies in DNA viruses. Homologous recombination is a universal genetic process that plays multiple roles in... (Review)
Review
The purpose of this review is to explore recombination strategies in DNA viruses. Homologous recombination is a universal genetic process that plays multiple roles in the biology of all organisms, including viruses. Recombination and DNA replication are interconnected, with recombination being essential for repairing DNA damage and supporting replication of the viral genome. Recombination also creates genetic diversity, and viral recombination mechanisms have important implications for understanding viral origins as well as the dynamic nature of viral-host interactions. Both bacteriophage λ and herpes simplex virus (HSV) display high rates of recombination, both utilizing their own proteins and commandeering cellular proteins to promote recombination reactions. We focus primarily on λ and HSV, as they have proven amenable to both genetic and biochemical analysis and have recently been shown to exhibit some surprising similarities that will guide future studies.
Topics: Bacteriophage lambda; DNA Viruses; Genome, Viral; Recombination, Genetic; Simplexvirus
PubMed: 25002096
DOI: 10.1146/annurev-micro-091313-103424 -
Current Opinion in Virology Dec 2016Gene therapy applications depend on vector delivery and gene expression in the appropriate target cell. Vector infection relies on the distribution of natural virus... (Review)
Review
Gene therapy applications depend on vector delivery and gene expression in the appropriate target cell. Vector infection relies on the distribution of natural virus receptors that may either not be present on the desired target cell or distributed in a manner to give off-target gene expression. Some viruses display a very limited host range, while others, including herpes simplex virus (HSV), can infect almost every cell within the human body. It is often an advantage to retarget virus infectivity to achieve selective target cell infection. Retargeting can be achieved by (i) the inclusion of glycoproteins from other viruses that have a different host-range, (ii) modification of existing viral glycoproteins or coat proteins to incorporate peptide ligands or single-chain antibodies (scFvs) that bind to the desired receptor, or (iii) employing soluble adapters that recognize both the virus and a specific receptor on the target cell. This review summarizes efforts to target HSV using these three strategies.
Topics: Drug Carriers; Genetic Therapy; Genetic Vectors; Humans; Simplexvirus; Viral Tropism
PubMed: 27614209
DOI: 10.1016/j.coviro.2016.08.007 -
Traffic (Copenhagen, Denmark) Mar 2003The genomes of many viruses traffic into the nucleus, where they are either integrated into host chromosomes or maintained as episomal DNA and then transcriptionally... (Review)
Review
The genomes of many viruses traffic into the nucleus, where they are either integrated into host chromosomes or maintained as episomal DNA and then transcriptionally activated or silenced. Here, we discuss the existing evidence on how the lentiviruses, adenoviruses, herpesviruses, hepadnaviruses and autonomous parvoviruses enter the nucleus. Depending on the size of the capsid enclosing the genome, three principles of viral nucleic acids import are discussed. The first principle is that the capsid disassembles in the cytosol or in a docked state at the nuclear pore complex and a subviral genomic complex is trafficked through the pore. Second, the genome is injected from a capsid that is docked to the pore complex, and third, import factors are recruited to cytosolic capsids to increase capsid affinity to the pore complex, mediate translocation and allow disassembly in the nucleoplasm.
Topics: Active Transport, Cell Nucleus; Animals; DNA, Viral; Genome, Viral; Lentivirus; Retroviridae; Simplexvirus
PubMed: 12656986
DOI: 10.1034/j.1600-0854.2003.00114.x -
FEMS Microbiology Letters Jun 2018
Topics: History, 20th Century; History, 21st Century; Humans; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Simplexvirus; Viral Tropism
PubMed: 29873707
DOI: 10.1093/femsle/fny019 -
The Journal of Investigative Dermatology Jul 1984The most direct approach to elucidating the roles of herpes simplex virus (HSV) proteins in the viral replicative cycle has been to isolate temperature-sensitive,... (Review)
Review
The most direct approach to elucidating the roles of herpes simplex virus (HSV) proteins in the viral replicative cycle has been to isolate temperature-sensitive, cytolysis-resistant, and drug-resistant mutants that exhibit alterations in the synthesis or activity of these proteins. The development of procedures for the introduction of temperature-sensitive mutations into physically defined regions of the viral genome and for fine mapping of these mutations has proven especially valuable. Thus, (1) hydroxylamine mutagenesis of the HSV-1 BglII I fragment (coordinates 0.312-0.415) has facilitated the genetic and functional characterization of the gene for the major viral DNA-binding protein of 130 K molecular weight; (2) the selection of a mutant conditionally able to render infected cells resistant to immune cytolysis has led to identification of an HSV gene involved in the processing of viral glycoproteins; and (3) the combined use of temperature-sensitive and drug-resistant mutants has led to a better definition of the physical limits and functional domains of the gene for HSV DNA polymerase.
Topics: Chromosome Mapping; Cloning, Molecular; DNA, Viral; DNA-Binding Proteins; DNA-Directed DNA Polymerase; Drug Resistance, Microbial; Genes, Viral; Genetic Complementation Test; Glycoproteins; Mutation; Simplexvirus; Temperature; Viral Proteins
PubMed: 6330220
DOI: 10.1111/1523-1747.ep12281154 -
International Journal of Experimental... Oct 2004Herpes simplex virus (HSV)-based vectors have primarily been developed for neuronal gene delivery, taking advantage of the virus' natural neurotropism. Two types of... (Review)
Review
Herpes simplex virus (HSV)-based vectors have primarily been developed for neuronal gene delivery, taking advantage of the virus' natural neurotropism. Two types of vector are available: replication defective viruses, whose cytotoxicity has been abolished by deleting viral gene products, and amplicon vectors, which are plasmids packaged into HSV particles with the aid of a helper virus. In this review I discuss how the cytotoxicity of the wild-type virus has been abolished, the progress which has been made toward defining promoter elements capable of directing long-term transgene expression form the latent viral genome and some of the potential clinical uses of these versatile vectors.
Topics: Gene Targeting; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Humans; Nervous System Diseases; Plasmids; Simplexvirus
PubMed: 15312123
DOI: 10.1111/j.0959-9673.2004.00383.x -
Clinical Microbiology Reviews Jul 1997The clinical manifestations of herpes simplex virus infection generally involve a mild and localized primary infection followed by asymptomatic (latent) infection... (Review)
Review
The clinical manifestations of herpes simplex virus infection generally involve a mild and localized primary infection followed by asymptomatic (latent) infection interrupted sporadically by periods of recrudescence (reactivation) where virus replication and associated cytopathologic findings are manifest at the site of initial infection. During the latent phase of infection, viral genomes, but not infectious virus itself, can be detected in sensory and autonomic neurons. The process of latent infection and reactivation has been subject to continuing investigation in animal models and, more recently, in cultured cells. The initiation and maintenance of latent infection in neurons are apparently passive phenomena in that no virus gene products need be expressed or are required. Despite this, a single latency-associated transcript (LAT) encoded by DNA encompassing about 6% of the viral genome is expressed during latent infection in a minority of neurons containing viral DNA. This transcript is spliced, and the intron derived from this splicing is stably maintained in the nucleus of neurons expressing it. Reactivation, which can be induced by stress and assayed in several animal models, is facilitated by the expression of LAT. Although the mechanism of action of LAT-mediated facilitation of reactivation is not clear, all available evidence argues against its involving the expression of a protein. Rather, the most consistent models of action involve LAT expression playing a cis-acting role in a very early stage of the reactivation process.
Topics: Animals; Disease Models, Animal; Encephalitis; Gene Expression Regulation, Viral; Herpes Simplex; Herpesvirus 3, Human; Humans; In Situ Hybridization, Fluorescence; Mice; Neurons; Promoter Regions, Genetic; Rabbits; Simplexvirus; Virus Activation; Virus Latency
PubMed: 9227860
DOI: 10.1128/CMR.10.3.419