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Frontiers in Immunology 2023Recurrent glioma treatment is challenging due to molecular heterogeneity and treatment resistance commonly observed in these tumors. Researchers are actively pursuing... (Review)
Review
Recurrent glioma treatment is challenging due to molecular heterogeneity and treatment resistance commonly observed in these tumors. Researchers are actively pursuing new therapeutic strategies. Oncolytic viruses have emerged as a promising option. Oncolytic viruses selectively replicate within tumor cells, destroying them and stimulating the immune system for an enhanced anticancer response. Among Oncolytic viruses investigated for recurrent gliomas, oncolytic herpes simplex virus and oncolytic adenovirus show notable potential. Genetic modifications play a crucial role in optimizing their therapeutic efficacy. Different generations of replicative conditioned oncolytic human adenovirus and oncolytic HSV have been developed, incorporating specific modifications to enhance tumor selectivity, replication efficiency, and immune activation. This review article summarizes these genetic modifications, offering insights into the underlying mechanisms of Oncolytic viruses' therapy. It also aims to identify strategies for further enhancing the therapeutic benefits of Oncolytic viruses. However, it is important to acknowledge that additional research and clinical trials are necessary to establish the safety, efficacy, and optimal utilization of Oncolytic viruses in treating recurrent glioblastoma.
Topics: Humans; Simplexvirus; Adenoviridae; Neoplasm Recurrence, Local; Glioma; Oncolytic Viruses; Adenoviridae Infections
PubMed: 38022620
DOI: 10.3389/fimmu.2023.1285113 -
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 -
Atencion Primaria Oct 2023To review the latest published evidence on the vaccine used in our country against the herpes zoster virus, breaking down the results according to the efficacy,... (Observational Study)
Observational Study
OBJECTIVE
To review the latest published evidence on the vaccine used in our country against the herpes zoster virus, breaking down the results according to the efficacy, efficiency, effectiveness and safety of the vaccine. Include the current recommendations for vaccination.
DESIGN
Secondary review. Descriptive qualitative review. Review using the search term "herpes zoster vaccine" and "Adjuvanted recombinant Herpes Zoster subunit vaccine". Retrospective observational study.
DATA SOURCES
Embase, Medline and Google Scholar. Selection of studies Search criterion with the terms "Shingrix vaccine" and "Adjuvanted Herpes Zoster Subunit Vaccine". Search period 2013-2023. Studies classified as clinical trials or randomized clinical trials were selected. 21 published studies were evaluated. There were no exclusions.
RESULTS
The evaluated studies were found to be coherent and in all of them efficacy in adult individuals in preventing viral reactivation and in preventing complications was higher than 80%. The effectiveness of the vaccine after two doses was also higher than 80%. Cost-effectiveness studies were always favourable in adults, immunodepressed patients and individuals with chronic pathology. The safety of the vaccine was evaluated in the pivotal studies and in the post-commercialization studies that were undertaken (although there were few of the latter due to the short period of time studied). The safety profile of the vaccine is very high and in the case of severe adverse effects, their frequency was similar to that of a placebo.
CONCLUSIONS
We have a safe and effective vaccine against the herpes zoster virus that allows us to protect the most vulnerable population groups against this virus.
Topics: Adult; Humans; Herpesvirus 3, Human; Herpes Zoster; Herpes Zoster Vaccine; Vaccination; Vaccines, Subunit
PubMed: 37573820
DOI: 10.1016/j.aprim.2023.102710 -
Human Vaccines & Immunotherapeutics Dec 2023Herpes zoster (HZ) is a debilitating vaccine-preventable disease. Impairment of cell-mediated immunity, as observed with aging and immunosuppressive disorders and... (Review)
Review
Herpes zoster (HZ) is a debilitating vaccine-preventable disease. Impairment of cell-mediated immunity, as observed with aging and immunosuppressive disorders and therapies, increases risk. Recombinant zoster vaccine (RZV) is efficacious against HZ in adults aged ≥50 years in different settings, and in immunocompromised adults aged ≥18 years who are at increased risk of developing HZ. RZV is the first and only HZ vaccine approved for use in immunocompromised adults globally, including in Europe and the US. RZV has a clinically acceptable safety profile and elicits robust immune responses in adults aged ≥50 years, and in immunocompromised adults aged ≥18 years who are at increased risk of HZ. Additionally, RZV is efficacious against HZ complications such as post-herpetic neuralgia and HZ-related pain. This review updates knowledge from a randomized controlled trial setting on the efficacy, safety, immunogenicity, and impact on quality of life of RZV.
Topics: Adult; Humans; Adolescent; Herpes Zoster Vaccine; Quality of Life; Herpes Zoster; Neuralgia, Postherpetic; Herpesvirus 3, Human; Vaccines, Synthetic
PubMed: 37965770
DOI: 10.1080/21645515.2023.2278362 -
The Journal of Cell Biology Sep 2023Herpes simplex virus (HSV-1) progeny form in the nucleus and exit to successfully infect other cells. Newly formed capsids navigate complex chromatin architecture to...
Herpes simplex virus (HSV-1) progeny form in the nucleus and exit to successfully infect other cells. Newly formed capsids navigate complex chromatin architecture to reach the inner nuclear membrane (INM) and egress. Here, we demonstrate by transmission electron microscopy (TEM) that HSV-1 capsids traverse heterochromatin associated with trimethylation on histone H3 lysine 27 (H3K27me3) and the histone variant macroH2A1. Through chromatin profiling during infection, we revealed global redistribution of these marks whereby massive host genomic regions bound by macroH2A1 and H3K27me3 correlate with decreased host transcription in active compartments. We found that the loss of these markers resulted in significantly lower viral titers but did not impact viral genome or protein accumulation. Strikingly, we discovered that loss of macroH2A1 or H3K27me3 resulted in nuclear trapping of capsids. Finally, by live-capsid tracking, we quantified this decreased capsid movement. Thus, our work demonstrates that HSV-1 takes advantage of the dynamic nature of host heterochromatin formation during infection for efficient nuclear egress.
Topics: Cell Nucleus; Chromatin; Herpesvirus 1, Human; Heterochromatin; Histones; Virus Release; Capsid
PubMed: 37516914
DOI: 10.1083/jcb.202304106 -
Viruses May 2024Our current understanding of HSV latency is based on a variety of clinical observations, and in vivo, ex vivo, and in vitro model systems, each with unique advantages... (Review)
Review
Our current understanding of HSV latency is based on a variety of clinical observations, and in vivo, ex vivo, and in vitro model systems, each with unique advantages and drawbacks. The criteria for authentically modeling HSV latency include the ability to easily manipulate host genetics and biological pathways, as well as mimicking the immune response and viral pathogenesis in human infections. Although realistically modeling HSV latency is necessary when choosing a model, the cost, time requirement, ethical constraints, and reagent availability are also equally important. Presently, there remains a pressing need for in vivo models that more closely recapitulate human HSV infection. While the current in vivo, ex vivo, and in vitro models used to study HSV latency have limitations, they provide further insights that add to our understanding of latency. In vivo models have shed light on natural infection routes and the interplay between the host immune response and the virus during latency, while in vitro models have been invaluable in elucidating molecular pathways involved in latency. Below, we review the relative advantages and disadvantages of current HSV models and highlight insights gained through each.
Topics: Virus Latency; Humans; Herpes Simplex; Animals; Simplexvirus; Herpesvirus 1, Human; Disease Models, Animal
PubMed: 38793628
DOI: 10.3390/v16050747 -
Frontiers in Immunology 2023Herpes B virus is a biosafety level 4 pathogen and widespread in its natural host species, macaques. Although most infected monkeys show asymptomatic or mild symptoms,... (Review)
Review
Herpes B virus is a biosafety level 4 pathogen and widespread in its natural host species, macaques. Although most infected monkeys show asymptomatic or mild symptoms, human infections with this virus can cause serious neurological symptoms or fatal encephalomyelitis with a high mortality rate. Herpes B virus can be latent in the sensory ganglia of monkeys and humans, often leading to missed diagnoses. Furthermore, the herpes B virus has extensive antigen crossover with HSV, SA8, and HVP-2, causing false-positive results frequently. Timely diagnosis, along with methods with sensitivity and specificity, are urgent for research on the herpes B virus. The lack of a clear understanding of the host invasion and life cycle of the herpes B virus has led to slow progress in the development of effective vaccines and drugs. This review discusses the research progress and problems of the epidemiology of herpes B virus, detection methods and therapy, hoping to inspire further investigation into important factors associated with transmission of herpes B virus in macaques and humans, and arouse the development of effective vaccines or drugs, to promote the establishment of specific pathogen-free (SPF) monkeys and protect humans to effectively avoid herpes B virus infection.
Topics: Humans; Animals; Herpesvirus 1, Cercopithecine; Herpesviridae Infections; Macaca; Vaccines
PubMed: 38035092
DOI: 10.3389/fimmu.2023.1281384 -
Frontiers in Veterinary Science 2023Pseudorabies virus (PRV) belongs to the subfamily and serves as an exceptional animal model for investigating the infection mechanism of Herpes simplex virus type 1.... (Review)
Review
Pseudorabies virus (PRV) belongs to the subfamily and serves as an exceptional animal model for investigating the infection mechanism of Herpes simplex virus type 1. Notably, PRV has the capability to infect a wide range of mammals, including humans, highlighting its potential as an overlooked zoonotic pathogen. The attachment and entry steps of PRV into host cells are crucial to accomplish its life cycle, which involve numerous cellular factors. In this mini review, we offer a comprehensive summary of current researches pertaining to the role of cellular factors in PRV attachment and entry stages, with the overarching goal of advancing the development of novel antiviral agents against this pathogen.
PubMed: 38089700
DOI: 10.3389/fvets.2023.1314624 -
Brain : a Journal of Neurology Sep 2023Clinical features applicable to the entire spectrum of viral meningitis are limited, and prognostic factors for adverse outcomes are undetermined. This nationwide...
Clinical features applicable to the entire spectrum of viral meningitis are limited, and prognostic factors for adverse outcomes are undetermined. This nationwide population-based prospective cohort study included all adults with presumed and microbiologically confirmed viral meningitis in Denmark from 2015 until 2020. Prognostic factors for an unfavourable outcome (Glasgow Outcome Scale score of 1-4) 30 days after discharge were examined by modified Poisson regression. In total, 1066 episodes of viral meningitis were included, yielding a mean annual incidence of 4.7 episodes per 100 000 persons. Pathogens were enteroviruses in 419/1066 (39%), herpes simplex virus type 2 in 171/1066 (16%), varicella-zoster virus in 162/1066 (15%), miscellaneous viruses in 31/1066 (3%) and remained unidentified in 283/1066 (27%). The median age was 33 years (IQR 27-44), and 576/1066 (54%) were females. In herpes simplex virus type 2 meningitis, 131/171 (77%) were females. Immunosuppression [32/162 (20%)] and shingles [90/149 (60%)] were frequent in varicella-zoster virus meningitis. The triad of headache, neck stiffness and hyperacusis or photophobia was present in 264/960 (28%). The median time until lumbar puncture was 3.0 h (IQR 1.3-7.1), and the median CSF leucocyte count was 160 cells/µl (IQR 60-358). The outcome was unfavourable in 216/1055 (20%) 30 days after discharge. Using unidentified pathogen as the reference, the adjusted relative risk of an unfavourable outcome was 1.34 (95% CI 0.95-1.88) for enteroviruses, 1.55 (95% CI 1.00-2.41) for herpes simplex virus type 2, 1.51 (95% CI 0.98-2.33) for varicella-zoster virus and 1.37 (95% CI 0.61-3.05) for miscellaneous viruses. The adjusted relative risk of an unfavourable outcome was 1.34 (95% CI 1.03-1.75) for females. Timing of acyclovir or valacyclovir was not associated with the outcome in meningitis caused by herpes simplex virus type 2 or varicella-zoster virus. In summary, the outcome of viral meningitis was similar among patients with different aetiologies, including those with presumed viral meningitis but without an identified pathogen. Females had an increased risk of an unfavourable outcome. Early antiviral treatment was not associated with an improved outcome in meningitis caused by herpes simplex virus type 2 or varicella-zoster virus.
Topics: Female; Humans; Adult; Male; Prospective Studies; Prognosis; Meningitis, Viral; Herpesvirus 3, Human
PubMed: 36929167
DOI: 10.1093/brain/awad089 -
Fn-OMV potentiates ZBP1-mediated PANoptosis triggered by oncolytic HSV-1 to fuel antitumor immunity.Nature Communications Apr 2024Oncolytic viruses (OVs) show promise as a cancer treatment by selectively replicating in tumor cells and promoting antitumor immunity. However, the current...
Oncolytic viruses (OVs) show promise as a cancer treatment by selectively replicating in tumor cells and promoting antitumor immunity. However, the current immunogenicity induced by OVs for tumor treatment is relatively weak, necessitating a thorough investigation of the mechanisms underlying its induction of antitumor immunity. Here, we show that HSV-1-based OVs (oHSVs) trigger ZBP1-mediated PANoptosis (a unique innate immune inflammatory cell death modality), resulting in augmented antitumor immune effects. Mechanistically, oHSV enhances the expression of interferon-stimulated genes, leading to the accumulation of endogenous Z-RNA and subsequent activation of ZBP1. To further enhance the antitumor potential of oHSV, we conduct a screening and identify Fusobacterium nucleatum outer membrane vesicle (Fn-OMV) that can increase the expression of PANoptosis execution proteins. The combination of Fn-OMV and oHSV demonstrates potent antitumor immunogenicity. Taken together, our study provides a deeper understanding of oHSV-induced antitumor immunity, and demonstrates a promising strategy that combines oHSV with Fn-OMV.
Topics: Herpesvirus 1, Human; Oncolytic Viruses; Animals; Humans; Oncolytic Virotherapy; Mice; RNA-Binding Proteins; Cell Line, Tumor; Fusobacterium nucleatum; Neoplasms; Female; Immunity, Innate; Mice, Inbred BALB C
PubMed: 38693119
DOI: 10.1038/s41467-024-48032-7