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Frontiers in Public Health 2024We aimed to investigate the overlapping epidemiologies of human immunodeficiency virus (HIV), herpes simplex virus type 2 (HSV-2), chlamydia, gonorrhea, and syphilis in...
INTRODUCTION
We aimed to investigate the overlapping epidemiologies of human immunodeficiency virus (HIV), herpes simplex virus type 2 (HSV-2), chlamydia, gonorrhea, and syphilis in sexual networks of men who have sex with men (MSM), and to explore to what extent the epidemiology of one sexually transmitted infection (STI) relates to or differs from that of another STI.
METHODS
An individual-based Monte Carlo simulation model was employed to simulate the concurrent transmission of STIs within diverse sexual networks of MSM. The model simulated sexual partnering, birth, death, and STI transmission within each specific sexual network. The model parameters were chosen based on the current knowledge and understanding of the natural history, transmission, and epidemiology of each considered STI. Associations were measured using the Spearman's rank correlation coefficient (SRCC) and maximal information coefficient (MIC).
RESULTS
A total of 500 sexual networks were simulated by varying the mean and variance of the number of partners for both short-term and all partnerships, degree correlation, and clustering coefficient. HSV-2 had the highest current infection prevalence across the simulations, followed by HIV, chlamydia, syphilis, and gonorrhea. Threshold and saturation effects emerged in the relationship between STIs across the simulated networks, and all STIs demonstrated moderate to strong associations. The strongest current infection prevalence association was between HIV and gonorrhea, with an SRCC of 0.84 (95% CI: 0.80-0.87) and an MIC of 0.81 (95% CI: 0.74-0.88). The weakest association was between HSV-2 and syphilis, with an SRCC of 0.54 (95% CI: 0.48-0.59) and an MIC of 0.57 (95% CI, 0.49-0.65). Gonorrhea exhibited the strongest associations with the other STIs while syphilis had the weakest associations. Across the simulated networks, proportions of the population with zero, one, two, three, four, and five concurrent STI infections were 48.6, 37.7, 11.1, 2.4, 0.3, and < 0.1%, respectively. For lifetime exposure to these infections, these proportions were 13.6, 21.0, 22.9, 24.3, 13.4, and 4.8%, respectively.
CONCLUSION
STI epidemiologies demonstrate substantial overlap and associations, alongside nuanced differences that shape a unique pattern for each STI. Gonorrhea exhibits an "intermediate STI epidemiology," reflected by the highest average correlation coefficient with other STIs.
Topics: Male; Humans; Gonorrhea; Syphilis; Herpesvirus 2, Human; Homosexuality, Male; HIV; HIV Infections; Sexual and Gender Minorities; Sexually Transmitted Diseases; Chlamydia
PubMed: 38628844
DOI: 10.3389/fpubh.2024.1335693 -
Poultry Science Jun 2024The highly contagious, immunosuppressive, and cancer-causing Marek's disease virus (MDV) infects chickens. The financial costs of Marek's disease (MD) are significant...
The highly contagious, immunosuppressive, and cancer-causing Marek's disease virus (MDV) infects chickens. The financial costs of Marek's disease (MD) are significant for the chicken industry. In this study, a total of 180 samples from chicken farms suspected to be MDV-infected were collected. The chickens were sampled during the period between the months of October 2016 and February 2018 at Dakahlia and Damietta Governorates, Egypt. A total of 36 pooled samples were created. The prepared samples were inoculated into embryonated chicken eggs (ECEs). Indirect fluorescent antibody technique (IFAT) and ICP4 gene-based polymerase chain reaction (PCR) were used for MDV identification. For the genetic characterization of the identified virus, The ICP4 gene sequence was identified and compared with the sequences available from various regions of the world. Furthermore, the genomes of all detected MDVs were screened for the long terminal repeat (LTR) region of reticuloendotheliosis (REV) in their genomes. The results showed that 31 out of 36 pooled samples (86.1%) inoculated into ECEs displayed the characteristic pock lesions. By using IFAT and PCR to identify MDV in ECEs, positive results were found in 27 samples (75%). The Egyptian virus is thought to be genetically closely related to MDVs circulating in Ethiopia, China, and India. REV-LTR was amplified from 6 out of 27 field isolates genomes (22.2 %) while MDV vaccine strains were free from REV-LTR insertion. The integrated REV-LTRs depicted a close genetic relationship with those integrated in fowl poxvirus (FWPV) circulating in Egypt as well as those integrated in FWPVs and MDVs from China, USA, South Africa, and Australia. To the best of our knowledge, this investigation represents the first identification and characterization of REV-LTR insertions in Egyptian MDV field isolates. Given the findings above, additional research in the future seems crucial to determine how the REV-LTR insertions affect MDV pathogenesis, virulence, and insufficient vaccination protection.
Topics: Animals; Marek Disease; Chickens; Egypt; Poultry Diseases; Herpesvirus 2, Gallid; Terminal Repeat Sequences; Reticuloendotheliosis virus; Virus Integration; Genome, Viral
PubMed: 38626691
DOI: 10.1016/j.psj.2024.103722 -
European Journal of Histochemistry : EJH Apr 2024Antibody-based fluorescence analysis of female reproductive tissues in research of sexually transmitted diseases allows for an in-depth understanding of protein...
Walking a thin line between fixation and epitope binding - characterization of antigen retrieval methods suitable for eosinophil and HSV-2 staining in formalin-fixed female reproductive tissue.
Antibody-based fluorescence analysis of female reproductive tissues in research of sexually transmitted diseases allows for an in-depth understanding of protein localization, interactions, and pathogenesis. However, in many cases, cryosectioning is not compatible with biosafety regulations; at all times, exposure of lab personnel and the public to potentially harmful pathogens from biological infectious material must be avoided; thus, formaldehyde fixation is essential. Due to formaldehyde's cross-linking properties, protein detection with antibodies can be impeded. To allow effective epitope binding during immunofluorescence of formalin-fixed paraffin-embedded vaginal tissue, we investigated two antigen retrieval methods. We tested these methods regarding their suitability for automated image analysis, facilitating reproducible quantitative microscopic data acquisition in sexually transmitted disease research. Heat-based retrieval at 80°C in citrate buffer proved to increase antibody binding to eosinophil protein and HSV-2 visibly and tissue morphology best, and was the most efficient for sample processing and quantitative analysis.
Topics: Female; Humans; Formaldehyde; Epitopes; Herpesvirus 2, Human; Tissue Fixation; Eosinophils; Immunohistochemistry; Antigens; Staining and Labeling; Walking; Paraffin Embedding
PubMed: 38624064
DOI: 10.4081/ejh.2024.3929 -
PLoS Pathogens Apr 2024Viruses target mitochondria to promote their replication, and infection-induced stress during the progression of infection leads to the regulation of antiviral defenses...
Viruses target mitochondria to promote their replication, and infection-induced stress during the progression of infection leads to the regulation of antiviral defenses and mitochondrial metabolism which are opposed by counteracting viral factors. The precise structural and functional changes that underlie how mitochondria react to the infection remain largely unclear. Here we show extensive transcriptional remodeling of protein-encoding host genes involved in the respiratory chain, apoptosis, and structural organization of mitochondria as herpes simplex virus type 1 lytic infection proceeds from early to late stages of infection. High-resolution microscopy and interaction analyses unveiled infection-induced emergence of rough, thin, and elongated mitochondria relocalized to the perinuclear area, a significant increase in the number and clustering of endoplasmic reticulum-mitochondria contact sites, and thickening and shortening of mitochondrial cristae. Finally, metabolic analyses demonstrated that reactivation of ATP production is accompanied by increased mitochondrial Ca2+ content and proton leakage as the infection proceeds. Overall, the significant structural and functional changes in the mitochondria triggered by the viral invasion are tightly connected to the progression of the virus infection.
Topics: Mitochondria; Herpesvirus 1, Human; Humans; Herpes Simplex; Animals; Herpesviridae Infections; Disease Progression; Chlorocebus aethiops
PubMed: 38620036
DOI: 10.1371/journal.ppat.1011829 -
Cell Reports Apr 2024Interferon (IFN) contributes to the host's antiviral response by inducing IFN-stimulated genes (ISGs). However, their functional targets and the mechanism of action...
Interferon (IFN) contributes to the host's antiviral response by inducing IFN-stimulated genes (ISGs). However, their functional targets and the mechanism of action remain elusive. Here, we report that one such ISG, TRIM21, interacts with and degrades the TRPV2 channel in myeloid cells, reducing its expression and providing host protection against viral infections. Moreover, viral infection upregulates TRIM21 in paracrine and autocrine manners, downregulating TRPV2 in neighboring cells to prevent viral spread to uninfected cells. Consistently, the Trim21 mice are more susceptible to HSV-1 and VSV infection than the Trim21 littermates, in which viral susceptibility is rescued by inhibition or deletion of TRPV2. Mechanistically, TRIM21 catalyzes the K48-linked ubiquitination of TRPV2 at Lys295. TRPV2 is resistant to viral-infection-induced TRIM21-dependent ubiquitination and degradation, promoting viral infection more profoundly than wild-type TRPV2 when reconstituted into Lyz2-Cre;Trpv2 myeloid cells. These findings characterize targeting the TRIM21-TRPV2 axis as a conducive strategy to control viral spread to bystander cells.
Topics: Animals; Humans; Mice; Down-Regulation; HEK293 Cells; Herpesvirus 1, Human; Interferons; Mice, Inbred C57BL; Mice, Knockout; Myeloid Cells; Ribonucleoproteins; TRPV Cation Channels; Ubiquitination; Virus Diseases
PubMed: 38613787
DOI: 10.1016/j.celrep.2024.114095 -
International Journal of Molecular... Apr 2024Acute HSV-1 infection is associated with mild symptoms, such as fever and lesions of the mouth, face and skin. This phase is followed by a latency period before...
Acute HSV-1 infection is associated with mild symptoms, such as fever and lesions of the mouth, face and skin. This phase is followed by a latency period before reactivation, which is associated with symptoms ranging from ulcers to encephalitis. Despite available anti-HSV-1 drugs, the development of new antiviral agents is sought due to the presence of resistant viruses. Melatonin, a molecule secreted by the pineal gland, has been shown to be an antioxidant, inducer of antioxidant enzymes, and regulator of various biological processes. Clinical trials have explored its therapeutic utility in conditions including infections. This study focuses on melatonin's role in HSV-1 replication and the underlying mechanisms. Melatonin was found to decrease the synthesis of HSV-1 proteins in infected Vero cells measured by immunofluorescence, indicating an inhibition of HSV-1 replication. Additionally, it regulates the activities of antioxidant enzymes and affects proteasome activity. Melatonin activates the unfolded protein response (UPR) and autophagy and suppresses apoptosis in HSV-1-infected cells. In summary, melatonin demonstrates an inhibitory role in HSV-1 replication by modulating various cellular responses, suggesting its potential utility in the treatment of viral infections.
Topics: Chlorocebus aethiops; Animals; Melatonin; Antioxidants; Herpesvirus 1, Human; Vero Cells; Pineal Gland
PubMed: 38612846
DOI: 10.3390/ijms25074037 -
International Journal of Molecular... Mar 2024Herpes simplex virus type 1 (HSV-1) is a lifelong pathogen characterized by asymptomatic latent infection in the trigeminal ganglia (TG), with periodic outbreaks of cold...
Herpes simplex virus type 1 (HSV-1) is a lifelong pathogen characterized by asymptomatic latent infection in the trigeminal ganglia (TG), with periodic outbreaks of cold sores caused by virus reactivation in the TG and subsequent replication in the oral mucosa. While antiviral therapies can provide relief from cold sores, they are unable to eliminate HSV-1. We provide experimental results that highlight non-thermal plasma (NTP) as a new alternative therapy for HSV-1 infection that would resolve cold sores faster and reduce the establishment of latent infection in the TG. Additionally, this study is the first to explore the use of NTP as a therapy that can both treat and prevent human viral infections. The antiviral effect of NTP was investigated using an in vitro model of HSV-1 epithelial infection that involved the application of NTP from two separate devices to cell-free HSV-1, HSV-1-infected cells, and uninfected cells. It was found that NTP reduced the infectivity of cell-free HSV-1, reduced viral replication in HSV-1-infected cells, and diminished the susceptibility of uninfected cells to HSV-1 infection. This triad of antiviral mechanisms of action suggests the potential of NTP as a therapeutic agent effective against HSV-1 infection.
Topics: Humans; Herpesvirus 1, Human; Herpes Labialis; Herpes Simplex; Keratinocytes; Latent Infection; Antiviral Agents
PubMed: 38612649
DOI: 10.3390/ijms25073839 -
Journal of Veterinary Internal Medicine 2024Equine herpesvirus myeloencephalopathy (EHM) has severe impact on the sport horse population.
Long-term performance of show-jumping horses and relationship with severity of ataxia and complications associated with myeloencephalopathy caused by equine herpes virus-1.
BACKGROUND
Equine herpesvirus myeloencephalopathy (EHM) has severe impact on the sport horse population.
OBJECTIVE
Study the influence of EHM on the likelihood of affected horses to return to their previous performance and investigate the association of clinical variables with prognosis.
ANIMALS
Twenty-six horses positive for equine herpesvirus type 1 (EHV-1) were admitted to a veterinary teaching hospital (VTH) during a natural EHM outbreak at an international jumping event.
METHODS
Data collected from the VTH, the International Equestrian Federation, and surveys completed by the riders and horse owners were retrospectively analyzed.
RESULTS
Horses affected by EHM had 68% chance of returning to exercise, and 52.9% were able to achieve their preoutbreak performance level. Horses with an ataxia grade at admission ≥4/5 had an increased fatality rate (P < .05) and 10% chance of reaching their preoutbreak performance level. None of the horses with both vascular and urinary complications returned to their previous performance level. Finally, horses vaccinated against EHV-1 and those with urinary complications had a 71.4% and 43.7% fatality rate, respectively.
CONCLUSIONS AND CLINICAL IMPORTANCE
Horses affected by EHM were able to return to their previous performance levels, but certain clinical variables were negatively associated with postoutbreak performance. Ataxia grade upon admission and the development of systemic signs of vasculitis and urinary complications were potential poor prognostic indicators in sport horses. Variables linked to fatality included prior vaccination against EHV-1, ataxia grade upon admission, and the development of urinary complications.
Topics: Animals; Horses; Herpesvirus 1, Equid; Horse Diseases; Ataxia; Retrospective Studies; Herpesviridae Infections; Male; Female; Physical Conditioning, Animal; Sports
PubMed: 38609161
DOI: 10.1111/jvim.17070 -
Digital Journal of Ophthalmology : DJO 2024Laboratory confirmation is crucial for diagnosis and management of herpes simplex virus (HSV) keratitis. However, the sensitivity of polymerase chain reaction (PCR) in...
BACKGROUND
Laboratory confirmation is crucial for diagnosis and management of herpes simplex virus (HSV) keratitis. However, the sensitivity of polymerase chain reaction (PCR) in keratitis is low (25%) compared with that of mucocutaneous disease (75%). We developed an educational intervention aimed at improving the diagnostic yield of PCR.
METHODS
The medical records of keratitis cases seen at the emergency department of a London tertiary ophthalmic referral hospital over two distinct periods, before and after an educational program on swab technique, were reviewed retrospectively.
RESULTS
A total of 252 HSV cases were included. Increases in the laboratory-confirmed diagnosis of HSV-1 were observed, in both first presentations (11.1%-57.7%) and recurrent cases (20%-57.6%). The rate of positive HSV-1 PCR in eyes with an epithelial defect increased from 19% pre-intervention to 62% post intervention. Notably, 3% were positive for varicella zoster virus DNA, and there was a single case of keratitis.
CONCLUSION
Our results suggest that, with proper swabbing technique, PCR may be more sensitive than previously reported.
Topics: Humans; Pilot Projects; Retrospective Studies; DNA, Viral; Keratitis, Herpetic; Herpesvirus 1, Human; Polymerase Chain Reaction; Herpes Simplex
PubMed: 38601900
DOI: 10.5693/djo.01.2024.01.002 -
Journal For Immunotherapy of Cancer Apr 2024Glioblastoma (GBM), a highly immunosuppressive and often fatal primary brain tumor, lacks effective treatment options. GBMs contain a subpopulation of GBM stem-like...
BACKGROUND
Glioblastoma (GBM), a highly immunosuppressive and often fatal primary brain tumor, lacks effective treatment options. GBMs contain a subpopulation of GBM stem-like cells (GSCs) that play a central role in tumor initiation, progression, and treatment resistance. Oncolytic viruses, especially oncolytic herpes simplex virus (oHSV), replicate selectively in cancer cells and trigger antitumor immunity-a phenomenon termed the "in situ vaccine" effect. Although talimogene laherparepvec (T-VEC), an oHSV armed with granulocyte macrophage-colony stimulating factor (GM-CSF), is Food and Drug Administration (FDA)-approved for melanoma, its use in patients with GBM has not been reported. Interleukin 2 (IL-2) is another established immunotherapy that stimulates T cell growth and orchestrates antitumor responses. IL-2 is FDA-approved for melanoma and renal cell carcinoma but has not been widely evaluated in GBM, and IL-2 treatment is limited by its short half-life, minimal tumor accumulation, and significant systemic toxicity. We hypothesize that local intratumoral expression of IL-2 by an oHSV would avoid the systemic IL-2-related therapeutic drawbacks while simultaneously producing beneficial antitumor immunity.
METHODS
We developed G47Δ-mIL2 (an oHSV expressing IL-2) using the flip-flop HSV BAC system to deliver IL-2 locally within the tumor microenvironment (TME). We then tested its efficacy in orthotopic mouse GBM models (005 GSC, CT-2A, and GL261) and evaluated immune profiles in the treated tumors and spleens by flow cytometry and immunohistochemistry.
RESULTS
G47Δ-mIL2 significantly prolonged median survival without any observable systemic IL-2-related toxicity in the 005 and CT-2A models but not in the GL261 model due to the non-permissive nature of GL261 cells to HSV infection. The therapeutic activity of G47Δ-mIL2 in the 005 GBM model was associated with increased intratumoral infiltration of CD8 T cells, critically dependent on the release of IL-2 within the TME, and CD4 T cells as their depletion completely abrogated therapeutic efficacy. The use of anti-PD-1 immune checkpoint blockade did not improve the therapeutic outcome of G47Δ-mIL2.
CONCLUSIONS
Our findings illustrate that G47Δ-mIL2 is efficacious, stimulates antitumor immunity against orthotopic GBM, and may also target GSC. OHSV expressing IL-2 may represent an agent that merits further exploration in patients with GBM.
Topics: Animals; Humans; Mice; Brain Neoplasms; CD8-Positive T-Lymphocytes; Glioblastoma; Herpes Simplex; Herpesvirus 2, Human; Interleukin-2; Melanoma; Oncolytic Virotherapy; Tumor Microenvironment; United States
PubMed: 38599661
DOI: 10.1136/jitc-2024-008880