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Current Protocols Jul 2023Our ability to understand the function of the nervous system is dependent upon defining the connections of its constituent neurons. Development of methods to define... (Review)
Review
Our ability to understand the function of the nervous system is dependent upon defining the connections of its constituent neurons. Development of methods to define connections within neural networks has always been a growth industry in the neurosciences. Transneuronal spread of neurotropic viruses currently represents the best means of defining synaptic connections within neural networks. The method exploits the ability of viruses to invade neurons, replicate, and spread through the intimate synaptic connections that enable communication among neurons. Since the method was first introduced in the 1970s, it has benefited from an increased understanding of the virus life cycle, the function of viral genomes, and the ability to manipulate the viral genome in support of directional spread of virus and the expression of transgenes. In this article, we review these advances in viral tracing technology and the ways in which they may be applied for functional dissection of neural networks. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Retrograde infection of CNS circuits by peripheral injection of virus Basic Protocol 2: Transneuronal analysis by intracerebral injection Alternate Protocol 1: Transneuronal analysis with multiple recombinant strains Alternate Protocol 2: Conditional replication and spread of PRV Alternate Protocol 3: Conditional reporters of PRV infection and spread Alternate Protocol 4: Reporters of neural activity in polysynaptic circuits Support Protocol 1: Growing and titering a PRV viral stock Support Protocol 2: Immunohistochemical processing and detection Support Protocol 3: Dual-immunofluorescence localization.
Topics: Animals; Herpesvirus 1, Suid; Neurons
PubMed: 37486157
DOI: 10.1002/cpz1.841 -
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 -
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 virus infections are a major concern after solid organ transplantation and linked to the immune function of the recipient. We aimed to determine the incidence of...
INTRODUCTION
Herpes virus infections are a major concern after solid organ transplantation and linked to the immune function of the recipient. We aimed to determine the incidence of positive herpes virus (cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus type 1/2 (HSV-1/2), and varicella zoster virus (VZV)) PCR tests during the first year post-transplantation and assess whether a model including immune function pre-transplantation and three months post-transplantation could predict a subsequent positive herpes virus PCR.
METHODS
All participants were preemptively screened for CMV, and EBV IgG-negative participants were screened for EBV during the first year post-transplantation. Herpes virus PCR tests for all included herpes viruses (CMV, EBV, HSV-1/2, and VZV) were retrieved from the Danish Microbiology database containing nationwide PCR results from both hospitals and outpatient clinics. Immune function was assessed by whole blood stimulation with A) LPS, B) R848, C) Poly I:C, and D) a blank control. Cytokine concentrations (TNF-α, IL-1β, IL-6, IL-8, IL-10, IL-12p40, IL-17A, IFN-α, and IFN-γ) were measured using Luminex.
RESULTS
We included 123 liver (54%), kidney (26%), and lung (20%) transplant recipients. The cumulative incidence of positive herpes virus PCR tests was 36.6% (95% CI: 28.1-45.1) during the first year post-transplantation. The final prediction model included recipient age, type of transplantation, CMV serostatus, and change in Poly I:C-induced IL-12p40 from pre-transplantation to three months post-transplantation. The prediction model had an AUC of 77% (95% CI: 61-92). Risk scores were extracted from the prediction model, and the participants were divided into three risk groups. Participants with a risk score <5 (28% of the cohort), 5-10 (45% of the cohort), and >10 (27% of the cohort) had a cumulative incidence of having a positive herpes virus PCR test at 5.8%, 25%, and 73%, respectively (p < 0.001).
CONCLUSION
In conclusion, the incidence of positive herpes virus PCR tests was high, and a risk model including immune function allowed the prediction of positive herpes virus PCR and may be used to identify recipients at higher risk.
Topics: Humans; Infant; Prospective Studies; Interleukin-12 Subunit p40; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Herpesviridae Infections; Organ Transplantation; Cytomegalovirus; Herpesvirus 3, Human; Herpesvirus 2, Human; Cytomegalovirus Infections; Immunity; Poly I
PubMed: 37465673
DOI: 10.3389/fimmu.2023.1183703 -
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 -
Scientific Reports Nov 2023Primary membranous nephropathy (MN) is a rare autoimmune cause of kidney failure. Observational studies have suggested some relationship between virus infection and...
Primary membranous nephropathy (MN) is a rare autoimmune cause of kidney failure. Observational studies have suggested some relationship between virus infection and primary MN, but the association remains unclear. The current study performed a two‑sample Mendelian randomization (MR) analysis to explore the causal association between varicella-zoster virus (VZV) infection (chickenpox and shingles) and primary MN using genome‑wide association studies (GWASs) summary statistics. The exposure datasets containing chickenpox and shingles were obtained from the GWASs conducted by the 23andMe cohort. And summary-level statistics for primary MN were used as the outcome dataset, comprising 2150 cases and 5829 controls from European Ancestry. The inverse variance weighted method was adopted as the main analysis. As a result, we found that both genetically determined chickenpox (odds ratio [95% confidential interval] = 3.61 [1.74-7.50], p = 5.59e-04) and shingles (p = 7.95e-03, odds ratio [95% confidential interval] = 2.49 [1.27-4.91]) were causally associated with an increased risk of developing primary MN. In conclusion, our MR findings provided novel genetic evidence supporting the causal effect of VZV infection on primary MN. Further studies are needed to elucidate the underlying mechanisms mediating the causal association.
Topics: Humans; Herpesvirus 3, Human; Chickenpox; Genome-Wide Association Study; Mendelian Randomization Analysis; Glomerulonephritis, Membranous; Herpes Zoster
PubMed: 37932291
DOI: 10.1038/s41598-023-46517-x -
Journal of Virology Jun 2023Pseudorabies virus (PRV) is a double-stranded DNA virus that causes Aujeszky's disease and is responsible for economic loss worldwide. Transmembrane protein 41B...
Pseudorabies virus (PRV) is a double-stranded DNA virus that causes Aujeszky's disease and is responsible for economic loss worldwide. Transmembrane protein 41B (TMEM41B) is a novel endoplasmic reticulum (ER)-localized regulator of autophagosome biogenesis and lipid mobilization; however, the role of TMEM41B in regulating PRV replication remains undocumented. In this study, PRV infection was found to upregulate TMEM41B mRNA and protein levels both and . For the first time, we found that TMEM41B could be induced by interferon (IFN), suggesting that TMEM41B is an IFN-stimulated gene (ISG). While TMEM41B knockdown suppressed PRV proliferation, TMEM41B overexpression promoted PRV proliferation. We next studied the specific stages of the virus life cycle and found that TMEM41B knockdown affected PRV entry. Mechanistically, we demonstrated that the knockdown of TMEM41B blocked PRV-stimulated expression of the key enzymes involved in lipid synthesis. Additionally, TMEM41B knockdown played a role in the dynamics of lipid-regulated PRV entry-dependent clathrin-coated pits (CCPs). Lipid replenishment restored the CCP dynamic and PRV entry in TMEM41B knockdown cells. Together, our results indicate that TMEM41B plays a role in PRV infection via regulating lipid homeostasis. PRV belongs to the alphaherpesvirus subfamily and can establish and maintain a lifelong latent infection in pigs. As such, an intermittent active cycle presents great challenges to the prevention and control of PRV disease and is responsible for serious economic losses to the pig breeding industry. Studies have shown that lipids play a crucial role in PRV proliferation. Thus, the manipulation of lipid metabolism may represent a new perspective for the prevention and treatment of PRV. In this study, we report that the ER transmembrane protein TMEM41B is a novel ISG involved in PRV infection by regulating lipid synthesis. Therefore, our findings indicate that targeting TMEM41B may be a promising approach for the development of PRV vaccines and therapeutics.
Topics: Animals; Herpesvirus 1, Suid; Interferons; Lipids; Pseudorabies; Swine; Virus Replication; Membrane Proteins
PubMed: 37255475
DOI: 10.1128/jvi.00412-23 -
Virology Journal Dec 2023Cervical cancer (CC) is one of the most common gynecologic tumors among women around the world. Although the etiological role of human papillomavirus (HPV) in CC is well... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cervical cancer (CC) is one of the most common gynecologic tumors among women around the world. Although the etiological role of human papillomavirus (HPV) in CC is well established, other factors in CC carcinogenesis remains unclear. Here, we performed a systematic review and meta-analysis to explore the association between infections of human herpesvirus (HHVs) and CC risk.
METHODS
Embase and PubMed databases were utilized to search the relevant studies. The revised JBI Critical Appraisal Tool was used to assess the quality of the included studies. Prevalence and odds ratios (ORs) with 95% confidence intervals (CI) were calculated to evaluate the association between viral infection and CC or precancerous cervical lesions (PCL).
RESULTS
Totally 67 eligible studies involving 7 different HHVs were included in meta-analysis. We found an increased risk of CC or PCL that was associated with the overall infection of HHVs (CC, OR = 2.74, 95% CI 2.13-3.53; PCL, OR = 1.95, 95% CI 1.58-2.41). Subgroup analysis showed a trend towards positive correlations between herpes simplex virus type 2 (HSV-2) infection and CC (OR = 3.01, 95% CI 2.24 to 4.04) or PCL (OR = 2.14, 95% CI 1.55 to 2.96), and the same is true between Epstein-Barr virus (EBV) infection and CC (OR = 4.89, 95% CI 2.18 to 10.96) or PCL (OR = 3.55, 95% CI 2.52 to 5.00). However, for HSV-1 and cytomegalovirus (HCMV), there was no association between viral infection and CC or PCL. By contrast, the roles of HHV-6, HHV-7, and Kaposi sarcoma-associated herpesvirus (KSHV) in cervical lesions were unclear due to the limited number of studies.
CONCLUSIONS
This study provided evidence that HHVs infection as a whole increase the risk of CC incidence. In addition, some types of HHVs such as EBV and HSV-2 may serve as potential targets in the development of new interventions or therapeutic strategies for cervical lesions.
Topics: Humans; Female; Epstein-Barr Virus Infections; Uterine Cervical Neoplasms; Herpesvirus 4, Human; Herpesviridae Infections; Herpesviridae; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human
PubMed: 38049836
DOI: 10.1186/s12985-023-02234-5 -
EMBO Reports Dec 2023Stimulator of interferon (IFN) genes (STING, also named MITA, ERIS, MPYS, or TMEM173) plays an essential role in DNA virus- or cytosolic DNA-triggered innate immune...
Stimulator of interferon (IFN) genes (STING, also named MITA, ERIS, MPYS, or TMEM173) plays an essential role in DNA virus- or cytosolic DNA-triggered innate immune responses. Here, we demonstrate that the RING-in-between RING (RBR) E3 ubiquitin ligase family member RING-finger protein (RNF) 144A interacts with STING and promotes its K6-linked ubiquitination at K236, thereby enhancing STING translocation from the ER to the Golgi and downstream signaling pathways. The K236R mutant of STING displays reduced activity in promoting innate immune signal transduction. Overexpression of RNF144A upregulates HSV-1- or cytosolic DNA-induced immune responses, while knockdown of RNF144A expression has the opposite effect. In addition, Rnf144a-deficient cells exhibit impaired DNA virus- or cytosolic DNA-triggered signaling, and RNF144A protects mice from DNA virus infection. In contrast, RNF144A does not affect RNA virus- or cytosolic RNA-triggered innate immune responses. Taken together, our findings identify a new positive regulator of DNA virus- or cytosolic DNA-triggered signaling pathways and a critical ubiquitination site important for fully functional STING during antiviral responses.
Topics: Animals; Mice; DNA; Herpesvirus 1, Human; Immunity, Innate; Ubiquitination
PubMed: 37955227
DOI: 10.15252/embr.202357528