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PLoS Pathogens Jun 2024Multiple functions are associated with HSV-1 latency associated transcript (LAT), including establishment of latency, virus reactivation, and antiapoptotic activity. LAT...
The anti-apoptotic function of HSV-1 LAT in neuronal cell cultures but not its function during reactivation correlates with expression of two small non-coding RNAs, sncRNA1&2.
Multiple functions are associated with HSV-1 latency associated transcript (LAT), including establishment of latency, virus reactivation, and antiapoptotic activity. LAT encodes two sncRNAs that are not miRNAs and previously it was shown that they have antiapoptotic activity in vitro. To determine if we can separate the antiapoptotic function of LAT from its latency-reactivation function, we deleted sncRNA1 and sncRNA2 sequences in HSV-1 strain McKrae, creating ΔsncRNA1&2 recombinant virus. Deletion of the sncRNA1&2 in ΔsncRNA1&2 virus was confirmed by complete sequencing of ΔsncRNA1&2 virus and its parental virus. Replication of ΔsncRNA1&2 virus in tissue culture or in the eyes of WT infected mice was similar to that of HSV-1 strain McKrae (LAT-plus) and dLAT2903 (LAT-minus) viruses. The levels of gB DNA in trigeminal ganglia (TG) of mice latently infected with ΔsncRNA1&2 virus was intermediate to that of dLAT2903 and McKrae infected mice, while levels of LAT in TG of latently infected ΔsncRNA1&2 mice was significantly higher than in McKrae infected mice. Similarly, the levels of LAT expression in Neuro-2A cells infected with ΔsncRNA1&2 virus was significantly higher than in McKrae infected cells. Reactivation in TG of ΔsncRNA1&2 infected mice was similar to that of McKrae and time of reactivation in both groups were significantly faster than dLAT2903 infected mice. However, levels of apoptosis in Neuro-2A cells infected with ΔsncRNA1&2 virus was similar to that of dLAT2903 and significantly higher than that of McKrae infected cells. Our results suggest that the antiapoptotic function of LAT resides within the two sncRNAs, which works independently of its latency-reactivation function and it has suppressive effect on LAT expression in vivo and in vitro.
Topics: Animals; Mice; Herpesvirus 1, Human; Apoptosis; Virus Activation; Neurons; Virus Latency; RNA, Viral; RNA, Small Untranslated; Cells, Cultured; Female; MicroRNAs
PubMed: 38857310
DOI: 10.1371/journal.ppat.1012307 -
PLoS Pathogens Jun 2024HSV infects keratinocytes in the epidermis of skin via nectin-1. We established a human foreskin explant infection model to investigate HSV entry and spread. HSV1 entry...
HSV infects keratinocytes in the epidermis of skin via nectin-1. We established a human foreskin explant infection model to investigate HSV entry and spread. HSV1 entry could only be achieved by the topical application of virus via high density microarray projections (HD-MAPs) to the epidermis, which penetrated beyond one third of its thickness, simulating in vivo microtrauma. Rapid lateral spread of HSV1 to a mean of 13 keratinocytes wide occurred after 24 hours and free virus particles were observed between keratinocytes, consistent with an intercellular route of spread. Nectin-1 staining was markedly decreased in foci of infection in the epidermis and in the human keratinocyte HaCaT cell line. Nectin-1 was redistributed, at the protein level, in adjacent uninfected cells surrounding infection, inducible by CCL3, IL-8 (or CXCL8), and possibly CXCL10 and IL-6, thus facilitating spread. These findings provide the first insights into HSV1 entry and spread in human inner foreskin in situ.
Topics: Humans; Male; Keratinocytes; Foreskin; Nectins; Herpes Simplex; Chemokines; Herpesvirus 1, Human; Cell Adhesion Molecules; Virus Internalization
PubMed: 38857290
DOI: 10.1371/journal.ppat.1012267 -
Reviews in Medical Virology Jul 2024Stroke is a common worldwide cause of death and disability, resulting from an obstruction or reduction in blood flow to the brain. Research has demonstrated that... (Meta-Analysis)
Meta-Analysis Review
Stroke is a common worldwide cause of death and disability, resulting from an obstruction or reduction in blood flow to the brain. Research has demonstrated that systemic infection such as herpes zoster (HZ) / ophthalmicus herpes zoster (HZO) can potentially trigger stroke. This study includes an updated systematic review and meta-analysis of the epidemiologic data on the connection between HZ/HZO infection and the risk of stroke. A meticulous search of different database yielded 905 studies. Furthermore, an additional 14 studies from a previous meta-analysis were incorporated. Eligible studies underwent rigorous screening, resulting in 18 papers. Statistical analyses, including random/fixed effects models and subgroup analyses, were conducted to assess pooled relative risk (RR) and heterogeneity. The meta-analysis consisted of 5,505,885 participants and found a statistically significant association between HZ infection and the risk of stroke (pooled RR = 1.22, 95% confidence interval [CI] 1.12-1.34). The HZO infection showed a significantly higher overall pooled RR of 1.71 (95% CI 1.06-2.75), indicating a strong connection with the risk of stroke. Subgroup analysis revealed that the odds ratio might play a significant role in causing heterogeneity. Time since infection emerged as a crucial factor, with heightened stroke risk in the initial year post-HZ/HZO exposure, followed by a decline after the first year. Asian/Non-Asian studies demonstrated varied results in HZ/HZO patients. Meta-analysis reveals a significant HZ/HZO-stroke link. Subgroups highlight varied risks and warrant extended Asian/non-Asian patient investigation.
Topics: Humans; Stroke; Herpes Zoster; Risk Assessment; Risk Factors; Herpesvirus 3, Human
PubMed: 38853706
DOI: 10.1002/rmv.2556 -
Voprosy Virusologii May 2024Herpes simplex virus type 1 (HSV-1) is one of the most common human viral infections and has a double-stranded DNA genome belonging to the Herpesviridae family. Smoking...
INTRODUCTION
Herpes simplex virus type 1 (HSV-1) is one of the most common human viral infections and has a double-stranded DNA genome belonging to the Herpesviridae family. Smoking is one of the leading causes of disease and premature death worldwide, responsible for the death of up to six million people annually. The purpose of the current study was to determine the seroprevalence of HSV-1 infection among smokers. Methods. The search strategy was conducted in the period from December 2022 to January 2023. The study included a random sample of 94 (88 males, and 6 females) healthy participants, aged between ≤ 20 to ≥ 60 years, with 50 participants as the control group. The HSV serological testing consisted of detecting antibodies to HSV-1 IgG with the help of ELISA.
RESULTS
Most participants were university students, consisting of 45.7% males and 5.3% females, followed by employed smokers, consisting of 0.2% males and 1.1% females. The number of females was much lower than that of males reaching 6.4 and 93.6% respectively, due to customs and traditions. The seroprevalence was 24.47, 22.3 and 2.1% in males and females respectively. The seroprevalence rate was 13.8% in hookah and cigarette smokers, 9% in cigarette smokers and 1.1% in hookah smokers exclusively. The highest rate was observed in the age groups of 21-30 and 31-40 years with 12.80% and 7.40% respectively.
CONCLUSIONS
The study revealed that the seroprevalence of HSV-1 IgG was 24.47%, and was higher among hookah and cigarette smokers compared to those who exclusively smoked cigarettes or hookah.
Topics: Humans; Male; Herpesvirus 1, Human; Female; Seroepidemiologic Studies; Adult; Middle Aged; Herpes Simplex; Smokers; Antibodies, Viral; Immunoglobulin G; Young Adult; Smoking; Aged; Adolescent
PubMed: 38843024
DOI: 10.36233/0507-4088-220 -
Anales de Pediatria Jun 2024
Topics: Humans; Infant, Newborn; Herpesvirus 2, Human; Acute Disease; Herpes Simplex; Male; Female
PubMed: 38834437
DOI: 10.1016/j.anpede.2024.05.006 -
BMC Infectious Diseases Jun 2024Herpes simplex encephalitis (HSE) is an important central nervous infection with severe neurological sequelae. The aim of this study was to describe clinical...
BACKGROUND
Herpes simplex encephalitis (HSE) is an important central nervous infection with severe neurological sequelae. The aim of this study was to describe clinical characteristic and outcomes of patients with HSE in Vietnam.
METHODS
This was a retrospective study of 66 patients with herpes simplex encephalitis who admitted to the National Hospital for Tropical Diseases, Hanoi, Vietnam from 2018 to 2021. The detection of herpes simplex virus (HSV) in cerebrospinal fluid was made by the real-time PCR assay. We reported the clinical manifestation on admission and evaluated clinical outcomes at the hospital discharge by modified Rankin Scale (mRS). Multivariate logistic regression analysis was used to analyze the independent risk factors of severe outcomes.
RESULTS
Of the 66 patients with laboratory confirmed HSE, the median age was 53 years (IQR 38-60) and 44 patients (69.7%) were male. The most common manifestations included fever (100%), followed by the consciousness disorder (95.5%). Other neurological manifestation were seizures (36.4%), memory disorders (31.8%), language disorders (19.7%) and behavioral disorders (13.6%). Conventional magnetic resonance imaging (MRI) showed 93.8% patients with temporal lobe lesions, followed by abnormalities in insula (50%), frontal lobe (34.4%) and 48.4% of patients had bilateral lesions. At discharge, 19 patients (28.8%) completely recovered, 15 patients (22.7%) had mild sequelae, 28 patients (42.4%) had moderate to severe sequelae. Severe neurological sequelae were memory disorders (55.8%), movement disorders (53.5%), language disorders (30.2%). Multivariate logistic regression analysis showed that Glasgow score decrement at admission, seizures, and time duration from onset of symptoms to the start of Acyclovir treatment > 4 days were independent factors associated with severe outcomes in HSE patients.
CONCLUSION
Glasgow score decrement, seizures and delay treatment with Acyclovir were associated with the poor outcome of patients with HSE.
Topics: Humans; Male; Female; Middle Aged; Retrospective Studies; Vietnam; Adult; Encephalitis, Herpes Simplex; Antiviral Agents; Simplexvirus; Risk Factors; Magnetic Resonance Imaging; Acyclovir; Treatment Outcome
PubMed: 38831304
DOI: 10.1186/s12879-024-09453-3 -
PLoS Pathogens Jun 2024Proper transcription regulation by key transcription factors, such as IRF3, is critical for anti-viral defense. Dynamics of enhancer activity play important roles in...
Proper transcription regulation by key transcription factors, such as IRF3, is critical for anti-viral defense. Dynamics of enhancer activity play important roles in many biological processes, and epigenomic analysis is used to determine the involved enhancers and transcription factors. To determine new transcription factors in anti-DNA-virus response, we have performed H3K27ac ChIP-Seq and identified three transcription factors, NR2F6, MEF2D and MAFF, in promoting HSV-1 replication. NR2F6 promotes HSV-1 replication and gene expression in vitro and in vivo, but not dependent on cGAS/STING pathway. NR2F6 binds to the promoter of MAP3K5 and activates AP-1/c-Jun pathway, which is critical for DNA virus replication. On the other hand, NR2F6 is transcriptionally repressed by c-Jun and forms a negative feedback loop. Meanwhile, cGAS/STING innate immunity signaling represses NR2F6 through STAT3. Taken together, we have identified new transcription factors and revealed the underlying mechanisms involved in the network between DNA viruses and host cells.
Topics: Immunity, Innate; Humans; Animals; Herpesvirus 1, Human; Mice; Virus Replication; Herpes Simplex; Signal Transduction; HEK293 Cells; Repressor Proteins
PubMed: 38829910
DOI: 10.1371/journal.ppat.1012271 -
Journal For Immunotherapy of Cancer May 2024Cytokines are small proteins that regulate the growth and functional activity of immune cells, and several have been approved for cancer therapy. Oncolytic viruses are... (Review)
Review
Cytokines are small proteins that regulate the growth and functional activity of immune cells, and several have been approved for cancer therapy. Oncolytic viruses are agents that mediate antitumor activity by directly killing tumor cells and inducing immune responses. Talimogene laherparepvec is an oncolytic herpes simplex virus type 1 (oHSV), approved for the treatment of recurrent melanoma, and the virus encodes the human cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF). A significant advantage of oncolytic viruses is the ability to deliver therapeutic payloads to the tumor site that can help drive antitumor immunity. While cytokines are especially interesting as payloads, the optimal cytokine(s) used in oncolytic viruses remains controversial. In this review, we highlight preliminary data with several cytokines and chemokines, including GM-CSF, interleukin 12, FMS-like tyrosine kinase 3 ligand, tumor necrosis factor α, interleukin 2, interleukin 15, interleukin 18, chemokine (C-C motif) ligand 2, chemokine (C-C motif) ligand 5, chemokine (C-X-C motif) ligand 4, or their combinations, and show how these payloads can further enhance the antitumor immunity of oHSV. A better understanding of cytokine delivery by oHSV can help improve clinical benefit from oncolytic virus immunotherapy in patients with cancer.
Topics: Humans; Oncolytic Virotherapy; Oncolytic Viruses; Cytokines; Immunotherapy; Neoplasms; Animals; Simplexvirus; Herpesvirus 1, Human
PubMed: 38821716
DOI: 10.1136/jitc-2023-008025 -
International Immunopharmacology Jul 2024The Ramsay-Hunt syndrome results from reactivation of the varicella-zoster virus at the geniculate ganglion level. The syndrome is characterized by a combination of...
The Ramsay-Hunt syndrome results from reactivation of the varicella-zoster virus at the geniculate ganglion level. The syndrome is characterized by a combination of symptoms such as ipsilateral facial paralysis, otalgia, and vesicles near the ear and auditory canal. The gold standard in the treatment of Ramsay-Hunt syndrome remains the combination of antiviral therapy with corticosteroids and adequate analgesic therapy. We present a case of a 45-year-old patient with severe form of atopic dermatitis, who developed this syndrome during treatment with dupilumab. The risks and benefits of dupilumab treatment in this patient were considered. Because both bronchial asthma and atopic dermatitis worsened when dupilumab was discontinued, it was indicated to continue this therapy with low-dose of acyclovir.
Topics: Humans; Antibodies, Monoclonal, Humanized; Middle Aged; Dermatitis, Atopic; Herpes Zoster Oticus; Male; Antiviral Agents; Herpesvirus 3, Human; Acyclovir; Asthma
PubMed: 38820959
DOI: 10.1016/j.intimp.2024.112345 -
Journal of Infection and Public Health Jul 2024A. baumannii is an important and common clinical pathogen, especially in the intensive care unit (ICU). This study aimed to characterize one hypervirulent A. baumannii...
BACKGROUND
A. baumannii is an important and common clinical pathogen, especially in the intensive care unit (ICU). This study aimed to characterize one hypervirulent A. baumannii strain in a patient with community-acquired pneumonia and herpes simplex type 1 virus infection.
METHODS
Minimum inhibitory concentrations (MICs) were determined using the Kirby-Bauer (K-B) and broth microdilution methods. Galleria mellonella infection model experiment was conducted. Whole-genome sequencing (WGS) was performed using the Illumina and Nanopore platforms. The resistance and virulence determinants were identified using the ABRicate program with ResFinder and the VFDB database. The capsular polysaccharide locus (K locus) and lipooligosaccharide outer core locus (OC locus) were identified using Kleborate with Kaptive. Phylogenetic analyses were conducted using the BacWGSTdb server.
RESULTS
A. baumannii XH2146 strain belongs to ST10 and ST447. The strain was resistant to cefazolin, ciprofloxacin, and trimethoprim/sulfamethoxazole (TMP-SMX). Bautype and Kaptive analyses showed that XH2146 contains OCL2 and KL49. WGS analysis revealed that the strain harbored bla, bla, ant(3'')-IIa, tet(B), and sul2. Notably, tet(B) and sul2, both were located within a 114,700-bp plasmid (designated pXH2146-1). Virulence assay revealed A. baumannii XH2146 possessed higher virulence than A. baumannii AB5075 at 12 h. Comparative genomic analysis showed that A. baumannii ST447 strains were mainly isolated from the USA and exhibited a relatively close genetic relationship. Importantly, 11 strains were observed to carry bla; bla was identified in 11 isolates and three ST447 A. baumannii strains harbored bla.
CONCLUSIONS
Early detection of community-acquired hypervirulent Acinetobacter baumannii strains is recommended to prevent their extensive spread in hospitals.
Topics: Community-Acquired Infections; Humans; Acinetobacter baumannii; China; Acinetobacter Infections; Microbial Sensitivity Tests; Animals; Whole Genome Sequencing; Phylogeny; Virulence; Herpesvirus 1, Human; Anti-Bacterial Agents; Virulence Factors; Herpes Simplex; Pneumonia, Bacterial; Male; Genome, Bacterial; Moths
PubMed: 38820896
DOI: 10.1016/j.jiph.2024.05.044