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1.
Int J Mol Sci ; 25(5)2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38474070

RESUMO

The herpesviral nuclear egress represents an essential step of viral replication efficiency in host cells, as it defines the nucleocytoplasmic release of viral capsids. Due to the size limitation of the nuclear pores, viral nuclear capsids are unable to traverse the nuclear envelope without a destabilization of this natural host-specific barrier. To this end, herpesviruses evolved the regulatory nuclear egress complex (NEC), composed of a heterodimer unit of two conserved viral NEC proteins (core NEC) and a large-size extension of this complex including various viral and cellular NEC-associated proteins (multicomponent NEC). Notably, the NEC harbors the pronounced ability to oligomerize (core NEC hexamers and lattices), to multimerize into higher-order complexes, and, ultimately, to closely interact with the migrating nuclear capsids. Moreover, most, if not all, of these NEC proteins comprise regulatory modifications by phosphorylation, so that the responsible kinases, and additional enzymatic activities, are part of the multicomponent NEC. This sophisticated basis of NEC-specific structural and functional interactions offers a variety of different modes of antiviral interference by pharmacological or nonconventional inhibitors. Since the multifaceted combination of NEC activities represents a highly conserved key regulatory stage of herpesviral replication, it may provide a unique opportunity towards a broad, pan-antiherpesviral mechanism of drug targeting. This review presents an update on chances, challenges, and current achievements in the development of NEC-directed antiherpesviral strategies.


Assuntos
Citomegalovirus , Herpesviridae , Citomegalovirus/metabolismo , Membrana Nuclear/metabolismo , Proteínas Virais/metabolismo , Herpesviridae/metabolismo , Fosforilação , Simplexvirus/metabolismo , Núcleo Celular/metabolismo
2.
J Med Virol ; 96(3): e29538, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38506230

RESUMO

To compare prevalence of positive PCR tests for herpesviruses between patients with and without a history of clinical corneal endothelial allograft rejection (AGR). Retrospective cross-sectional study with two-group comparison. A total of 307 aqueous humor (AH) samples from 235 Patients and 244 eyes who underwent penetrating keratoplasty or Descemet membrane endothelial keratoplasty or had a diagnostic AH aspiration due to clinical AGR between 2019 and 2023 were tested for DNA of herpes simplex virus (HSV), varicella-zoster virus (VZV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV). PCR test results were compared between the two groups (with/without AGR). Another sub-analysis examined the results of patients without a history of herpetic keratitis. A total of 8% of eyes with clinical AGR (9/108) had a positive PCR result for one of the herpesviruses (HSV:3, CMV:3, EBV:2, VZV:1). All patients in the group without AGR had negative PCR results for all previous viruses (0/136). The difference was statistically significant (p < 0.001). The sub-analysis of eyes without a history of herpetic keratitis also revealed significantly more positive herpes PCR results (7/87) in eyes with AGR than in eyes without AGR (0/42, p = 0.005). Clinical AGR after keratoplasty shows a significant correlation to viral replication. Herpetic infection and AGR could occur simultaneously and act synergistically. Timely differentiation between active herpetic infection and/or AGR is pivotal for proper treatment and graft preservation.


Assuntos
Infecções por Citomegalovirus , Infecções por Vírus Epstein-Barr , Infecções por Herpesviridae , Ceratite Herpética , Humanos , Estudos Retrospectivos , Humor Aquoso/química , Rejeição de Enxerto/diagnóstico , Estudos Transversais , Herpesvirus Humano 4/genética , Simplexvirus/genética , Citomegalovirus/genética , Infecções por Herpesviridae/diagnóstico , Herpesvirus Humano 3/genética , Reação em Cadeia da Polimerase , DNA Viral/genética , DNA Viral/análise
3.
Alzheimers Res Ther ; 16(1): 57, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38475873

RESUMO

BACKGROUND: In this study, the risk of dementia in patients with a history of herpes simplex virus (HSV) or varicella zoster virus (VZV) infection was evaluated. METHODS: This nationwide cohort study used data from the Korean National Health Insurance Service collected between 2006 and 2017. A total of 752,205 subjects ≥ 45 years of age not diagnosed with dementia until 2006 were included. A multivariate Cox regression model, adjusted for age, sex, and other comorbidities, was used to assess the hazard ratio (HR) for dementia based on VZV or HSV infection. The interaction effects of both viral infections were analysed. Viral infections are classified into four categories: eye, central nervous system (CNS), simple, and complicated. The hazard ratio (HR) of viral infection was analysed based on the type of dementia. RESULTS: In multivariable analysis, both HSV and VZV infection were associated with an increased risk of dementia (HR = 1.38, 95% confidence interval, CI:1.33-1.43) and (HR = 1.41, 95% CI:1.37-1.46), respectively. Patients who experienced both HSV and VZV infections were also at an increased risk of dementia (HR = 1.57, 95% CI:1.50-1.63). The co-infection group showed the shortest time from viral infection to dementia diagnosis (4.09 ± 3.02 years). In the subgroup analysis, all types of HSV and VZV infections were associated with an increased risk of dementia compared to the non-infection group. The eye, CNS, and complicated VZV infections were associated with a significantly higher risk than simple VZV infections. There were no significant differences between the subtypes of HSV infection. Furthermore, HSV, VSV, and co-infection were associated with an increased risk of all dementia types, including Alzheimer's disease (AD) and vascular dementia (VD). CONCLUSIONS: Individual HSV and VZV infections were associated with an increased risk of all types of dementia, including AD and VD. Patients co-infected with HSV and VZV, VZV infection in the eye, CNS, or complicated type were more vulnerable to the development of dementia.


Assuntos
Coinfecção , Demência , Herpes Simples , Herpes Zoster , Viroses , Humanos , Herpesvirus Humano 3 , Simplexvirus , Estudos de Coortes , Estudos Retrospectivos
4.
BMJ Case Rep ; 17(3)2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38458763

RESUMO

We report a baby with neonatal herpes simplex virus (HSV) encephalitis concurrent with Rrhesus (Rh) incompatibility. He was delivered by a Ggravida 2 mother with a history of miscarriage in her previous pregnancy at a gestation age of 4 months. She had Bblood group 0 and Rrhesus negative. The baby was noticed to have jaundice on day one1 of life accompanied by generalised petechiae on the face and upper chest. A full blood picture revealed severe anaemia and severe thrombocytopaenia and HSV 1/2 IgM was positive. MRI of the brain showed multiple extensive haemorrhagic lesions on the frontal-temporal regions.


Assuntos
Encefalite por Herpes Simples , Herpes Simples , Complicações Infecciosas na Gravidez , Masculino , Recém-Nascido , Lactente , Gravidez , Feminino , Humanos , Herpes Simples/complicações , Herpes Simples/diagnóstico , Herpes Simples/tratamento farmacológico , Encefalite por Herpes Simples/complicações , Complicações Infecciosas na Gravidez/diagnóstico , Simplexvirus
5.
BMC Infect Dis ; 24(1): 273, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38431567

RESUMO

BACKGROUND: Human herpesviruses are widespread among the human population. The infections often occur unnoticed, but severe disease as well as long-term sequelae are part of the symptom spectrum. The prevalence varies among subpopulations and with time. The aim of this study was to describe the seroprevalence of Immunoglobulin G against Herpes simplex 1, Herpes simplex 2, Epstein-Barr virus and Cytomegalovirus in the adult Swedish population over a time period of several decades. METHODS: Serum samples (n = 892) from biobanks, originating from 30-year-old women, 50-year-old men and 50-year-old women sampled between 1975 and 2018, were analyzed for presence of anti-herpesvirus antibodies. Linear regression analysis was used to test for a correlation between birth year and seroprevalence. Multiple linear regression analysis was used to differentiate between other factors such as age and gender. RESULTS: Birth year correlated negatively with the prevalence of immunoglobulin G against Herpes simplex 1 and Epstein-Barr virus (p = 0.004 and 0.033), and positively with Immunoglobulin G against Cytomegalovirus (p = 0.039). When participant categories were analyzed separately, birth year correlated negatively with the prevalence of Immunoglobulin G against Herpes simplex 1 and Herpes simplex 2 (p = 0.032 and 0.028) in 30-year-old women, and with the prevalence of Immunoglobulin G against Cytomegalovirus in 50-year-old men (p = 0.011). CONCLUSIONS: The prevalence of Immunoglobulin G against Herpes simplex 1, Herpes simplex 2 and Epstein-Barr virus decreases in later birth cohorts. This indicates a trend of declining risk of getting infected with these viruses as a child and adolescent.


Assuntos
Infecções por Vírus Epstein-Barr , Herpes Simples , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anticorpos Antivirais , Citomegalovirus , Infecções por Vírus Epstein-Barr/epidemiologia , Herpes Simples/epidemiologia , Herpesvirus Humano 4 , Imunoglobulina G , Estudos Soroepidemiológicos , Simplexvirus , Suécia/epidemiologia
6.
Med Clin North Am ; 108(2): 311-323, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38331482

RESUMO

Genital herpes is a chronic, lifelong sexually transmitted viral infection, which can cause recurrent, self-limited genital ulcers. It is caused by herpes simplex virus (HSV) type 1 and type 2 viruses. Genital HSV infection is a very prevalent STI, which causes self-limited, recurrent genital ulcers. Treatment decreases duration of symptoms and signs and can be provided as episodic or suppressive therapy. Genital herpes can have a substantial impact during pregnancy and on sexual health in general. Counseling on natural history, transmission, treatment, and management of sexual partners is an integral part of management of genital herpes.


Assuntos
Herpes Genital , Feminino , Gravidez , Humanos , Herpes Genital/diagnóstico , Herpes Genital/tratamento farmacológico , Simplexvirus , Úlcera , Aconselhamento , Atenção Primária à Saúde
7.
EMBO Rep ; 25(3): 1541-1569, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38263330

RESUMO

To globally profile circRNAs, we employ RNA-Sequencing paired with chimeric junction analysis for alpha-, beta-, and gamma-herpesvirus infection. We find circRNAs are, as a population, resistant to host shutoff. We validate this observation using ectopic expression assays of human and murine herpesvirus endoribonucleases. During lytic infection, four circRNAs are commonly induced across all subfamilies of human herpesviruses, suggesting a shared mechanism of regulation. We test one such mechanism, namely how interferon-stimulation influences circRNA expression. 67 circRNAs are upregulated by either interferon-ß or -γ treatment, with half of these also upregulated during lytic infection. Using gain and loss of function studies we find an interferon-stimulated circRNA, circRELL1, inhibits lytic Herpes Simplex Virus-1 infection. We previously reported circRELL1 inhibits lytic Kaposi sarcoma-associated herpesvirus infection, suggesting a pan-herpesvirus antiviral activity. We propose a two-pronged model in which interferon-stimulated genes may encode both mRNA and circRNA with antiviral activity. This is critical in cases of host shutoff, such as alpha- and gamma-herpesvirus infection, where the mRNA products are degraded but circRNAs escape.


Assuntos
Herpes Simples , Herpesviridae , Humanos , Camundongos , Animais , RNA Circular , Interferons , RNA Mensageiro , Simplexvirus , Antivirais
8.
Nat Commun ; 15(1): 131, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167409

RESUMO

Oncolytic virotherapy holds promise for cancer treatment, but the factors determining its oncolytic activity remain unclear. Neutrophil extracellular traps (NETs) are associated with cancer progression, yet their formation mechanism and role in oncolytic virotherapy remain elusive. In this study, we demonstrate that, in glioma, upregulation of IGF2BP3 enhances the expression of E3 ubiquitin protein ligase MIB1, promoting FTO degradation via the ubiquitin-proteasome pathway. This results in increased m6A-mediated CSF3 release and NET formation. Oncolytic herpes simplex virus (oHSV) stimulates IGF2BP3-induced NET formation in malignant glioma. In glioma models in female mice, a BET inhibitor enhances the oncolytic activity of oHSV by impeding IGF2BP3-induced NETosis, reinforcing virus replication through BRD4 recruitment with the CDK9/RPB-1 complex to HSV gene promoters. Our findings unveil the regulation of m6A-mediated NET formation, highlight oncolytic virus-induced NETosis as a critical checkpoint hindering oncolytic potential, and propose targeting NETosis as a strategy to overcome resistance in oncolytic virotherapy.


Assuntos
Glioma , Terapia Viral Oncolítica , Vírus Oncolíticos , Feminino , Camundongos , Animais , Terapia Viral Oncolítica/métodos , Resistencia a Medicamentos Antineoplásicos , Proteínas Nucleares , Fatores de Transcrição , Glioma/genética , Simplexvirus/genética , Vírus Oncolíticos/genética
9.
BMC Ophthalmol ; 24(1): 38, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38267915

RESUMO

BACKGROUND: To report a case of retinitis with multiple intraocular viral infections after second haematopoietic stem cell transplantation. CASE PRESENTATION: A 39-year-old female patient developed retinitis after a second haematopoietic stem cell transplant. Right eye was tested for three viral infections- cytomegalovirus, Epstein‒Barr virus and herpes simplex virus, while left was infected with cytomegalovirus. The patient was subsequently treated with vitreous cavity ganciclovir injections, and 1 week later both eyes tested negative for aqueous humour viruses. DISCUSSION AND CONCLUSION: CMV, EBV and HSV belong to the herpes virus family. They are all commonly observed in the body and represent opportunity infectious viruses. The retinitis they cause have different characteristics. But simultaneous infection of the eye by multiple viruses is quite rare. In this case, three viruses were detected in the patient's eye, but whether the retina was caused by all three viruses at the same time could not be determined. A satisfactory outcome was achieved after treatment with vitreous cavity ganciclovir injection.


Assuntos
Infecções por Vírus Epstein-Barr , Transplante de Células-Tronco Hematopoéticas , Retinite , Viroses , Feminino , Humanos , Adulto , Herpesvirus Humano 4 , Citomegalovirus , Simplexvirus , Infecções por Vírus Epstein-Barr/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Retina , Ganciclovir/uso terapêutico
10.
J Clin Rheumatol ; 30(1): 12-17, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37946328

RESUMO

BACKGROUND/OBJECTIVE: The potential correlation between herpes simplex virus (HSV) and human papillomavirus (HPV) infections and rheumatoid arthritis (RA) has not been definitively established. Further research is needed to determine the relationship between the development of RA and the presence of these viral infections. METHODS: A case-control study was conducted with data from the National Health and Nutrition Examination Survey between 2009 and 2014. Our analysis examined the association between HSV I, HSV II, HPV oral polymerase chain reaction (PCR), HPV vaginal PCR, and RA. We identified adults aged 20 to 49 years with a primary diagnosis of RA using the National Health and Nutrition Examination Survey database codes (MCQ191 = 1 [years 2009-2010]; MCQ195 = 2 [years 2011-2014]) and excluded patients with incomplete data on key variables and primary outcomes. RESULTS: The study included 8620 patients, with 150 patients diagnosed with RA and 1500 patients without RA. Patients with RA had a significantly higher prevalence of HSV II infection compared with those without RA (36.34% vs. 24.72%, p = 0.015) after propensity score matching. No significant differences were observed for HSV I, HPV oral PCR, and HPV vaginal PCR between the 2 groups. Patients with RA were older; were more likely to be female, obese, and non-Hispanic White; and had a higher prevalence of comorbidities than those without RA. CONCLUSIONS: This population-based propensity score-matching study provides evidence of an association between HSV II infection and RA in US adults. Further research is needed to fully elucidate the relationship between viral infections and RA, with the aim of developing effective risk reduction strategies and innovative treatments for RA.


Assuntos
Artrite Reumatoide , Herpes Simples , Infecções por Papillomavirus , Adulto , Humanos , Feminino , Masculino , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/complicações , Estudos de Casos e Controles , Inquéritos Nutricionais , Pontuação de Propensão , Herpes Simples/diagnóstico , Herpes Simples/epidemiologia , Herpes Simples/complicações , Simplexvirus , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/complicações
11.
Eye (Lond) ; 38(1): 61-67, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37419957

RESUMO

AIMS: To present current expert practice patterns and to formulate a consensus for the management of HSV and VZV AU by uveitis specialists worldwide. METHODS: A two-round online modified Delphi survey with masking of the study team was conducted. Responses were collected from 76 international uveitis experts from 21 countries. Current practices in the diagnosis and treatment of HSV and VZV AU were identified. A working group (The Infectious Uveitis Treatment Algorithm Network [TITAN]) developed data into consensus guidelines. Consensus is defined as a particular response towards a specific question meeting ≥75% of agreement or IQR ≤ 1 when a Likert scale is used. RESULTS: Unilaterality, increased intraocular pressure (IOP), decreased corneal sensation and diffuse or sectoral iris atrophy are quite specific for HSV or VZV AU from consensus opinion. Sectoral iris atrophy is characteristic of HSV AU. Treatment initiation is highly variable, but most experts preferred valacyclovir owing to simpler dosing. Topical corticosteroids and beta-blockers should be used if necessary. Resolution of inflammation and normalisation of IOP are clinical endpoints. CONCLUSIONS: Consensus was reached on several aspects of diagnosis, choice of initial treatment, and treatment endpoints for HSV and VZV AU. Treatment duration and management of recurrences varied between experts.


Assuntos
Herpes Simples , Herpes Zoster Oftálmico , Herpes Zoster , Uveíte Anterior , Uveíte , Humanos , Herpesvirus Humano 3 , Simplexvirus , Herpes Zoster Oftálmico/diagnóstico , Herpes Zoster Oftálmico/tratamento farmacológico , Uveíte Anterior/diagnóstico , Uveíte Anterior/tratamento farmacológico , Atrofia , Herpes Simples/diagnóstico , Herpes Simples/tratamento farmacológico
12.
Curr Pediatr Rev ; 20(3): 365-369, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-36809946

RESUMO

AIMS: The study aims to investigate the presence of TORCH infections in a child with bilateral cataracts and deafness and report the ToRCH-serology screening profile (Toxoplasma gondii (TOX), rubella (RV), cytomegalovirus (CMV), and herpes simplex virus (HSV-I/II)) in pediatric cataract and deafness. METHODS: Cases that had a clear clinical history of congenital cataracts and congenital deafness were included in the study. The study population consisted of 18 bilateral cataracts and 12 bilateral deafness child who was admitted to AIIMS Bhubaneswar for cataract surgery and cochlear implantation, respectively. Sera of all children were tested qualitatively and quantitatively for IgG/IgM-antibodies against ToRCH agents in a sequential manner. RESULTS: Anti-IgG antibodies against the torch panel were detected in all cataract and deafness patients. Anti-CMV IgG was detected in 17 of 18 bilateral cataract children and 11 of 12 bilateral deaf children. The rates of anti-CMV IgG antibody positivity were significantly higher. In the cataract group, 94.44% and in the deafness group, 91.66% of the patient was Anti-CMV IgG positive. Besides this, 77.7 % of the patient from the cataract group and 75% from the deafness group was anti- RV IgG antibody positive. In bilateral cataract patients, IgG-alone seropositive cases were mostly attributed to CMV (94.44%; 17/18), followed by RV (77.70%; 14/18), HSV-I (27.70%; 5/18), TOX (27.70%; 5/18), and HSV-II (16.60%; 3/18). In bilateral deafness patients, the spectrum of IgG alone seropositive cases was almost the same except for TOX (0/12). CONCLUSION: The current study recommends interpreting ToRCH-screening in pediatric cataracts and deafness with caution. Interpretation should include both serial qualitative and quantitative assays in tandem with clinical correlation to minimize diagnostic errors. The sero-clinical-positivity needs to be tested in older children who might pose a threat to the spread of infection.


Assuntos
Catarata , Infecções por Citomegalovirus , Surdez , Humanos , Criança , Estudos Soroepidemiológicos , Perda Auditiva Bilateral , Centros de Atenção Terciária , Citomegalovirus , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/epidemiologia , Simplexvirus , Imunoglobulina G , Anticorpos Antivirais , Catarata/epidemiologia
13.
Rev Med Virol ; 34(1): e2491, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37985599

RESUMO

The immunopathology of herpes simplex virus (HSV)-associated neuroinflammation is a captivating and intricate field of study within the scientific community. HSV, renowned for its latent infection capability, gives rise to a spectrum of neurological expressions, ranging from mild symptoms to severe encephalitis. The enigmatic interplay between the virus and the host's immune responses profoundly shapes the outcome of these infections. This review delves into the multifaceted immune reactions triggered by HSV within neural tissues, intricately encompassing the interplay between innate and adaptive immunity. Furthermore, this analysis delves into the delicate equilibrium between immune defence and the potential for immunopathology-induced neural damage. It meticulously dissects the roles of diverse immune cells, cytokines, and chemokines, unravelling the intricacies of neuroinflammation modulation and its subsequent effects. By exploring HSV's immune manipulation and exploitation mechanisms, this review endeavours to unveil the enigmas surrounding the immunopathology of HSV-associated neuroinflammation. This comprehensive understanding enhances our grasp of viral pathogenesis and holds promise for pioneering therapeutic strategies designed to mitigate the neurological ramifications of HSV infections.


Assuntos
Herpes Simples , Simplexvirus , Humanos , Doenças Neuroinflamatórias , Imunidade Adaptativa , Citocinas
15.
Sex Transm Infect ; 100(2): 106-107, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38124214

RESUMO

A gay man with well-controlled HIV and vaccinated against mpox presented with severe proctitis. Testing revealed anorectal mpox, herpes simplex virus, lymphogranuloma venereum, Neisseria gonorrhoeae and Mycoplasma genitalium Serology was indicative of infectious syphilis. This case highlights the need to consider a wide range of concurrent sexually transmitted infections in patients with proctitis, including those vaccinated against mpox.


Assuntos
Gonorreia , Infecções por HIV , Linfogranuloma Venéreo , Mycoplasma genitalium , Proctite , Sífilis , Masculino , Humanos , Linfogranuloma Venéreo/complicações , Linfogranuloma Venéreo/diagnóstico , Linfogranuloma Venéreo/tratamento farmacológico , Sífilis/complicações , Sífilis/diagnóstico , Sífilis/tratamento farmacológico , Gonorreia/complicações , Gonorreia/diagnóstico , Proctite/etiologia , Simplexvirus , Infecções por HIV/complicações , Homossexualidade Masculina
16.
J Virol Methods ; 324: 114874, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38154579

RESUMO

BACKGROUND: Varicella zoster virus (VZV) is the pathogen of varicella and herpes zoster, it is necessary to develop a rapid, sensitive and specific detection method for the prevention and control of related diseases. METHODS: We inserted the gB protein extracellular region gene (gB-ex, 1-2208 bp) of VZV into lentivirus vector, and then obtained the recombinant gB protein through mammalian expression system. BALB/c mice were immunized multiple times with purified gB protein as immunogen. Then four strains of high affinity monoclonal antibodies targeting gB protein were prepared by cell fusion technique. Monoclonal antibodies 5G4 and HRP-4E9 were selected as capture and detection antibodies respectively, and a double-antibody sandwich ELISA method was established for detection. RESULTS: The detection limit of the DAS-ELISA was 156 PFU/mL, and there was no cross-reaction with Herpes simplex virus-1/Herpes simplex virus-2/Pseudorabies virus. The coefficients of variation of intra-assay and inter-assay repeatability were less than 5%. CONCLUSIONS: In this study, a double-antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) was established for the detection of VZV. The assay has good sensitivity, specificity and repeatability, which provides strong technical support and product guarantee for the rapid clinical detection of VZV.


Assuntos
Herpes Zoster , Herpesvirus Humano 3 , Animais , Camundongos , Anticorpos Antivirais , Ensaio de Imunoadsorção Enzimática/métodos , Anticorpos Monoclonais , Simplexvirus , Proteínas Recombinantes , Mamíferos
17.
Ocul Surf ; 31: 21-30, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38122863

RESUMO

PURPOSE: Herpes simplex keratitis (HSK), caused by type 1 herpes simplex virus (HSV) reactivation, is a severe infectious disease that leads to vision loss. HSV can trigger metabolic reprogramming in the host cell and change the extracellular vesicles (EV) cargos; however, little is known about the EV metabolic signatures during ocular HSV infection. Here, we aimed to depict the EV-associated metabolic landscape in HSK patients' tears. METHODS: We collected 82 samples from 41 participants with unilateral HSK (contralateral unaffected tears were set as negative control), including subtype cohorts of 13 epithelial, 20 stromal, and 8 endothelial HSK. We isolated tear EVs via our previously established platform and conducted metabolic analysis using LC-MS/MS. The metabolic signatures for recognizing HSK and subtypes were assessed through differential analysis and machine learning algorithms. RESULTS: Hypopsia and increased extracellular CD63 levels were observed in affected eyes. We identified 339 metabolites based on sEVs isolated from tears. Differential analysis revealed alterations in energy and amino acid metabolism, as well as the infectious microenvironment. Furthermore, we observed dysregulated metabolite such as methyldopa, which is associated with inappropriate neovascularization and corneal sensation loss, contributing to the HSK severity particularly in the stromal subtype. Moreover, machine learning classification also suggested a set of EV metabolic signatures that have potential for pan-keratitis detection. CONCLUSIONS: Our findings demonstrate that tear EV metabolites can serve as valuable indicators for comprehending the underlying pathological mechanisms. This knowledge is expected to facilitate the development of liquid biopsy means and therapeutic target discovery.


Assuntos
Ceratite Herpética , Espectrometria de Massas em Tandem , Humanos , Cromatografia Líquida , Ceratite Herpética/diagnóstico , Córnea/metabolismo , Simplexvirus
18.
Transpl Infect Dis ; 25 Suppl 1: e14201, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38041493

RESUMO

Although hematopoietic stem cell transplantation (HSCT) and other cellular therapies have significantly improved outcomes in the management of multiple hematological and nonhematological malignancies, the resulting impairment in humoral and cellular response increases the risk for opportunistic infection as an undesirable side effect. With their ability to establish latent infection and reactivate when the host immune system is at its weakest point, the Herpesviridae family constitutes a significant proportion of these opportunistic pathogens. Despite recent advancements in preventing and managing herpesvirus infections, they continue to be a common cause of significant morbidity and mortality in transplanted patients. Herein, we aim to provide and update on herpesvirus other than cytomegalovirus (CMV) affecting recipients of HSCT and other cellular therapies.


Assuntos
Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Infecções por Herpesviridae , Herpesviridae , Humanos , Citomegalovirus , Simplexvirus , Transplante de Células-Tronco Hematopoéticas/efeitos adversos
20.
Molecules ; 28(23)2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-38067446

RESUMO

A quantitative analysis of the relationship between the structure and inhibitory activity against the herpes simplex virus thymidine kinase (HSV-TK) was performed for the series of 5-ethyluridine, N2-guanine, and 6-oxopurines derivatives with pronounced anti-herpetic activity (IC50 = 0.09 ÷ 160,000 µmol/L) using the GUSAR 2019 software. On the basis of the MNA and QNA descriptors and whole-molecule descriptors using the self-consistent regression, 12 statistically significant consensus models for predicting numerical pIC50 values were constructed. These models demonstrated high predictive accuracy for the training and test sets. Molecular fragments of HSV-1 and HSV-2 TK inhibitors that enhance or diminish the anti-herpetic activity are considered. Virtual screening of the ChEMBL database using the developed QSAR models revealed 42 new effective HSV-1 and HSV-2 TK inhibitors. These compounds are promising for further research. The obtained data open up new opportunities for developing novel effective inhibitors of TK.


Assuntos
Herpesvirus Humano 1 , Relação Quantitativa Estrutura-Atividade , Guanina/química , Timidina Quinase , Herpesvirus Humano 2 , Simplexvirus , Antivirais/farmacologia
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