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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 -
Immunity, Inflammation and Disease Oct 2023This study investigated the proteomic characteristics of cerebrospinal fluid (CSF) in patients with varicella zoster virus (VZV) meningitis to understanding the... (Review)
Review
OBJECTIVE
This study investigated the proteomic characteristics of cerebrospinal fluid (CSF) in patients with varicella zoster virus (VZV) meningitis to understanding the pathogenesis of central nervous system (CNS) infection by reactivated VZV.
METHOD
We used data-independent acquisition model to analyze the CSF proteomic differences of 28 patients with VZV meningitis and 11 herpes zoster (HZ) patients. According to the clinical manifestations at discharge, 28 VZV meningitis patients were divided into favorable outcome group and unfavorable outcome (UO) group and their differences in CSF proteome were also analyzed.
RESULTS
Compared with the HZ group, the proteins (CXCL10, ELANE, IL-1RN, MPO, PRTN3, etc.) related to inflammation and immune cell activation were significantly upregulated in the VZV meningitis group (p < .01). The protein related to the nerve function and energy metabolism (CKMT1B, SLITRK3, Synaptotagmin-3, KIF5B, etc.) were significantly downregulated (p < .05). The levels of a pro-inflammatory factor, IL-18, in CSF were significantly higher in patients in the UO group as compared to patients with favorable prognosis (p < .05).
CONCLUSION
Inflammatory immune response is an important pathophysiological mechanism of CNS infection by VZV, and the CSF IL-18 levels might be a potential prognostic indicator of the outcomes of VZV meningitis.
Topics: Humans; Herpesvirus 3, Human; Interleukin-18; Proteomics; Herpes Zoster; Meningitis; Proteins
PubMed: 37904697
DOI: 10.1002/iid3.1038 -
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 -
Nature Communications Dec 2023Herpesviruses remain a burden for animal and human health, including the medically important varicella-zoster virus (VZV). Membrane fusion mediated by conserved core...
Herpesviruses remain a burden for animal and human health, including the medically important varicella-zoster virus (VZV). Membrane fusion mediated by conserved core glycoproteins, the fusogen gB and the heterodimer gH-gL, enables herpesvirus cell entry. The ectodomain of gB orthologs has five domains and is proposed to transition from a prefusion to postfusion conformation but the functional relevance of the domains for this transition remains poorly defined. Here we describe structure-function studies of the VZV gB DIII central helix targeting residues EHV. Critically, a H527P mutation captures gB in a prefusion conformation as determined by cryo-EM, a loss of membrane fusion in a virus free assay, and failure of recombinant VZV to spread in cell monolayers. Importantly, two predominant cryo-EM structures of gB[H527P] are identified by 3D classification and focused refinement, suggesting they represented gB conformations in transition. These studies reveal gB DIII as a critical element for herpesvirus gB fusion function.
Topics: Animals; Humans; Viral Envelope Proteins; Mutagenesis; Mutation; Herpesvirus 3, Human; Herpesvirus 1, Human; Virus Internalization
PubMed: 38042814
DOI: 10.1038/s41467-023-43011-w -
Viruses Nov 2023Lung transplantation is an ultimate treatment option for some end-stage lung diseases; due to the intense immunosuppression needed to reduce the risk of developing acute... (Review)
Review
Lung transplantation is an ultimate treatment option for some end-stage lung diseases; due to the intense immunosuppression needed to reduce the risk of developing acute and chronic allograft failure, infectious complications are highly incident. Viral infections represent nearly 30% of all infectious complications, with herpes viruses playing an important role in the development of acute and chronic diseases. Among them, cytomegalovirus (CMV) is a major cause of morbidity and mortality, being associated with an increased risk of chronic lung allograft failure. Epstein-Barr virus (EBV) is associated with transformation of infected B cells with the development of post-transplantation lymphoproliferative disorders (PTLDs). Similarly, herpes simplex virus (HSV), varicella zoster virus and human herpesviruses 6 and 7 can also be responsible for acute manifestations in lung transplant patients. During these last years, new, highly sensitive and specific diagnostic tests have been developed, and preventive and prophylactic strategies have been studied aiming to reduce and prevent the incidence of these viral infections. In this narrative review, we explore epidemiology, diagnosis and treatment options for more frequent herpes virus infections in lung transplant patients.
Topics: Humans; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Herpesviridae Infections; Lung Transplantation; Herpesvirus 3, Human; Simplexvirus; Herpes Zoster
PubMed: 38140567
DOI: 10.3390/v15122326 -
Frontiers in Immunology 2023The coronavirus disease 2019 (COVID-19) has emerged as a main global public health challenge. Additionally, herpes simplex virus type-1 (HSV-1) and type 2 (HSV-2) are...
INTRODUCTION
The coronavirus disease 2019 (COVID-19) has emerged as a main global public health challenge. Additionally, herpes simplex virus type-1 (HSV-1) and type 2 (HSV-2) are widespread viruses that can cause orolabial herpes and genital herpes. Several clinical case reports have declared a possible association between the two, however, the causal relationship between them has not been clarified.
METHODS
This study utilized a Mendelian randomization (MR) approach for causality assessment between COVID-19 infection and HSV infection based on the latest public health data and Genome-Wide Association Study (GWAS) data. Multiple causal estimation methods, such as IVW, weighted median, simple mode, and weighted mode, were employed to validate the causal relation between COVID-19 infection and HSV infection, with COVID-19 infection, COVID-19 hospitalization, and severe COVID-19 as exposures, and HSV1/2 infection as the outcome. A reverse MR analysis was subsequently performed.
RESULTS
MR analysis exhibited that COVID-19 infection was relevant to a reduced risk of HSV1 infection (p=7.603239e-152, OR=0.5690, 95%CI=0.5455-0.5935, IVW). Regarding the effect of COVID-19 infection on HSV2, MR analysis suggested that COVID-19 infection was correlated with an augmented risk of HSV2 infection (p=6.46735e-11, OR=1.1137, 95%CI=1.0782-1.1502, IVW). The reverse MR analysis did not demonstrate a reverse causal relationship between HSV and COVID-19.
DISCUSSION
Altogether, COVID-19 infection might cause a decreased risk of HSV1 infection and an elevated risk of HSV2 infection.
Topics: Humans; Genome-Wide Association Study; Mendelian Randomization Analysis; COVID-19; Herpesvirus 1, Human; Herpes Simplex
PubMed: 38146366
DOI: 10.3389/fimmu.2023.1281292 -
Journal of Veterinary Internal Medicine 2024Equine herpesvirus-1 (EHV-1) is a highly prevalent and frequently pathogenic infection of equids. The most serious clinical consequences of infection are abortion and...
Equine herpesvirus-1 (EHV-1) is a highly prevalent and frequently pathogenic infection of equids. The most serious clinical consequences of infection are abortion and equine herpesvirus myeloencephalopathy (EHM). The previous consensus statement was published in 2009 and considered pathogenesis, strain variation, epidemiology, diagnostic testing, vaccination, outbreak prevention and control, and treatment. A recent survey of American College of Veterinary Internal Medicine large animal diplomates identified the need for a revision to this original consensus statement. This updated consensus statement is underpinned by 4 systematic reviews that addressed key questions concerning vaccination, pharmaceutical treatment, pathogenesis, and diagnostic testing. Evidence for successful vaccination against, or effective treatment of EHV-1 infection was limited, and improvements in experimental design and reporting of results are needed in future studies of this important disease. This consensus statement also updates the topics considered previously in 2009.
Topics: Animals; Herpesvirus 1, Equid; Horses; Horse Diseases; Herpesviridae Infections; Pregnancy; Female
PubMed: 38497217
DOI: 10.1111/jvim.17047 -
Nature Communications Jul 2023Prediction, prevention and treatment of virus infections require understanding of cell-to-cell variability that leads to heterogenous disease outcomes, but the source of...
Prediction, prevention and treatment of virus infections require understanding of cell-to-cell variability that leads to heterogenous disease outcomes, but the source of this heterogeneity has yet to be clarified. To study the multimodal response of single human cells to herpes simplex virus type 1 (HSV-1) infection, we mapped high-dimensional viral and cellular state spaces throughout the infection using multiplexed imaging and quantitative single-cell measurements of viral and cellular mRNAs and proteins. Here we show that the high-dimensional cellular state scape can predict heterogenous infections, and cells move through the cellular state landscape according to infection progression. Spatial information reveals that infection changes the cellular state of both infected cells and of their neighbors. The multiplexed imaging of HSV-1-induced cellular modifications links infection progression to changes in signaling responses, transcriptional activity, and processing bodies. Our data show that multiplexed quantification of responses at the single-cell level, across thousands of cells helps predict infections and identify new targets for antivirals.
Topics: Humans; Herpesvirus 1, Human; Herpes Simplex; Antiviral Agents; RNA, Messenger; Virus Replication
PubMed: 37500668
DOI: 10.1038/s41467-023-40148-6