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2.
PLoS Pathog ; 15(10): e1007956, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31589653

RESUMO

We report the analysis of a complex enveloped human virus, herpes simplex virus (HSV), assembled after in vivo incorporation of bio-orthogonal methionine analogues homopropargylglycine (HPG) or azidohomoalanine (AHA). We optimised protocols for the production of virions incorporating AHA (termed HSVAHA), identifying conditions which resulted in normal yields of HSV and normal particle/pfu ratios. Moreover we show that essentially every single HSVAHA capsid-containing particle was detectable at the individual particle level by chemical ligation of azide-linked fluorochromes to AHA-containing structural proteins. This was a completely specific chemical ligation, with no capsids assembled under normal methionine-containing conditions detected in parallel. We demonstrate by quantitative mass spectrometric analysis that HSVAHA virions exhibit no qualitative or quantitative differences in the repertoires of structural proteins compared to virions assembled under normal conditions. Individual proteins and AHA incorporation sites were identified in capsid, tegument and envelope compartments, including major essential structural proteins. Finally we reveal novel aspects of entry pathways using HSVAHA and chemical fluorochrome ligation that were not apparent from conventional immunofluorescence. Since ligation targets total AHA-containing protein and peptides, our results demonstrate the presence of abundant AHA-labelled products in cytoplasmic macrodomains and tubules which no longer contain intact particles detectable by immunofluorescence. Although these do not co-localise with lysosomal markers, we propose they may represent sites of proteolytic virion processing. Analysis of HSVAHA also enabled the discrimination from primary entering from secondary assembling virions, demonstrating assembly and second round infection within 6 hrs of initial infection and dual infections of primary and secondary virus in spatially restricted cytoplasmic areas of the same cell. Together with other demonstrated applications e.g., in genome biology, lipid and protein trafficking, this work further exemplifies the utility and potential of bio-orthogonal chemistry for studies in many aspects of virus-host interactions.


Assuntos
Aminoácidos/metabolismo , Herpes Simples/virologia , Herpesvirus Humano 1/fisiologia , Epitélio Pigmentado da Retina/virologia , Proteínas Estruturais Virais/metabolismo , Montagem de Vírus , Internalização do Vírus , Proliferação de Células , Células Cultivadas , Herpes Simples/metabolismo , Humanos , Epitélio Pigmentado da Retina/metabolismo
4.
Nature ; 571(7763): 122-126, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31189952

RESUMO

Antibodies secreted into mucosal barriers serve to protect the host from a variety of pathogens, and are the basis for successful vaccines1. In type I mucosa (such as the intestinal tract), dimeric IgA secreted by local plasma cells is transported through polymeric immunoglobulin receptors2 and mediates robust protection against viruses3,4. However, owing to the paucity of polymeric immunoglobulin receptors and plasma cells, how and whether antibodies are delivered to the type II mucosa represented by the lumen of the lower female reproductive tract remains unclear. Here, using genital herpes infection in mice, we show that primary infection does not establish plasma cells in the lamina propria of the female reproductive tract. Instead, upon secondary challenge with herpes simplex virus 2, circulating memory B cells that enter the female reproductive tract serve as the source of rapid and robust antibody secretion into the lumen of this tract. CD4 tissue-resident memory T cells secrete interferon-γ, which induces expression of chemokines, including CXCL9 and CXCL10. Circulating memory B cells are recruited to the vaginal mucosa in a CXCR3-dependent manner, and secrete virus-specific IgG2b, IgG2c and IgA into the lumen. These results reveal that circulating memory B cells act as a rapidly inducible source of mucosal antibodies in the female reproductive tract.


Assuntos
Anticorpos/imunologia , Linfócitos B/citologia , Linfócitos B/imunologia , Movimento Celular/imunologia , Memória Imunológica/imunologia , Vagina/citologia , Vagina/imunologia , Animais , Formação de Anticorpos/imunologia , Linfócitos T CD4-Positivos/imunologia , Feminino , Herpes Simples/imunologia , Herpes Simples/virologia , Herpesvirus Humano 2/imunologia , Imunização , Imunoglobulina A/imunologia , Imunoglobulina G/imunologia , Interferon gama/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Receptores CXCR3/imunologia , Vagina/virologia
6.
Indian J Ophthalmol ; 67(7): 1040-1046, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31238404

RESUMO

Purpose: To determine the presence of herpes simplex virus and varicella zoster virus (HSV 1 and 2, VZV) in the cornea of normal subjects by multiplex real time quantitative (qPCR) assay and evaluate its utility in the diagnosis of viral keratitis. Methods: Corneal epithelial cells from 33 eyes of 22 patients undergoing photorefractive keratectomy surgery (controls) and 50 corneal scrapings from 50 patients with suspected HSV keratitis were analyzed for the presence of HSV1 by conventional PCR and for presence of HSV1 and 2 and/or VZV by multiplex real-time PCR. Corneal scrapings of patients were also tested for HSV1 antigen by immunofluorescence assay (IFA). The results were compared and clinical records reviewed. Results: HSV1 and VZV DNA were detected in 8/33 controls (mean-14.3 ± 7.96, range: 3-29.1 copies/mL) and 2/33 controls (mean-10.7 ± 10.9, range 3-18.5 copies/ml) respectively. HSV2 was not detected in any of the controls. Copy numbers above the mean + 1SD of controls were considered significant for viral load in patient samples. Significantly higher number of corneal scrapings (39/50, 78%) from patients were positive for HSV1 (1.2 × 106 copies/mL ± 3.7 × 106 copies/mL) by real time qPCR compared to IFA (11/48, 23%, P value 0.0001) and conventional PCR (20/50, 40%, P value 0.0002). Double infection with HSV-1 (1.5 × 107 copies/ml) and HSV-2 (3.57 × 104 copies/ml) in one case and VZV infection (1.03 × 102 copies/ml) in another was also detected by the multiplex real-time PCR. Conclusion: Multiplex real-time PCR reliably detects HSV1 and 2 and VZV DNA and is ideal for the diagnosis of HSV and VZV keratitis in an ocular microbiology laboratory.


Assuntos
Infecções Oculares Virais/diagnóstico , Herpesvirus Humano 1/genética , Herpesvirus Humano 2/genética , Herpesvirus Humano 3/genética , Ceratite Herpética/diagnóstico , Reação em Cadeia da Polimerase em Tempo Real/métodos , Infecção pelo Vírus da Varicela-Zoster/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Córnea/patologia , Córnea/virologia , DNA Viral/análise , Infecções Oculares Virais/epidemiologia , Infecções Oculares Virais/virologia , Feminino , Seguimentos , Herpes Simples/diagnóstico , Herpes Simples/epidemiologia , Herpes Simples/virologia , Humanos , Índia/epidemiologia , Lactente , Ceratite Herpética/epidemiologia , Ceratite Herpética/virologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Infecção pelo Vírus da Varicela-Zoster/epidemiologia , Infecção pelo Vírus da Varicela-Zoster/virologia , Adulto Jovem
8.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 48(1): 89-101, 2019 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-31102363

RESUMO

Herpes simplex virus (HSV), including HSV-1 and HSV-2, is an important pathogen that can cause many diseases. Usually these diseases are recurrent and incurable. After lytic infection on the surface of peripheral mucosa, HSV can enter sensory neurons and establish latent infection during which viral replication ceases. Moreover, latent virus can re-enter the replication cycle by reactivation and return to peripheral tissues to start recurrent infection. This ability to escape host immune surveillance during latent infection and to spread during reactivation is a viral survival strategy and the fundamental reason why no drug can completely eradicate the virus at present. Although there are many studies on latency and reactivation of HSV, and much progress has been made, many specific mechanisms of the process remain obscure or even controversial due to the complexity of this process and the limitations of research models. This paper reviews the major results of research on HSV latency and reactivation, and discusses future research directions in this field.


Assuntos
Herpes Simples , Herpesvirus Humano 1 , Ativação Viral , Latência Viral , Herpes Simples/virologia , Herpesvirus Humano 1/fisiologia , Humanos , Ativação Viral/fisiologia , Latência Viral/fisiologia , Replicação Viral
9.
Am J Otolaryngol ; 40(4): 609-611, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31109807

RESUMO

The management of invasive fungal sinusitis differs greatly from the management of herpes simplex virus (HSV) of the nose in immunocompromised patients. However, the diagnosis may be uncertain and a delay in treatment can lead to mortality. Here we describe the successful medical management of a series of immunocompromised pediatric patients with HSV lesions of the nose with the initial concern for invasive fungal sinusitis. The diagnosis of HSV herpes was supported by positive polymerase chain reaction (PCR) testing of the nasal lesion. To our knowledge, these are the first cases described in the pediatric literature, emphasizing the need to include this entity on the differential.


Assuntos
Herpes Simples/diagnóstico , Doenças Nasais/diagnóstico , Aciclovir/administração & dosagem , Adolescente , Adulto , Antivirais/administração & dosagem , Criança , Diagnóstico Diferencial , Feminino , Herpes Simples/patologia , Herpes Simples/terapia , Herpes Simples/virologia , Humanos , Hospedeiro Imunocomprometido , Infusões Intravenosas , Infecções Fúngicas Invasivas/patologia , Leucemia de Células B , Masculino , Doenças Nasais/patologia , Doenças Nasais/terapia , Doenças Nasais/virologia , Seios Paranasais , Reação em Cadeia da Polimerase , Leucemia-Linfoma Linfoblástico de Células Precursoras , Sinusite/microbiologia , Sinusite/patologia , Resultado do Tratamento
10.
Acta Derm Venereol ; 99(9): 789-796, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31037311

RESUMO

Desmoplakin (DSP) and Desmoglein 1 (DSG1) variants result in skin barrier defects leading to erythroderma, palmoplantar keratoderma and variable [AQ4] other features. Some DSG1 variant carriers present with SAM syndrome (Severe dermatitis, multiple Allergies, Metabolic wasting) and a SAM-like phenotype has been reported in 4 subjects with different heterozygous DSP variants. We report here a patient with a novel DSP spectrin region (SR) 6 variant c.1756C>T, p.(His586Tyr), novel features of brain lesions and severe recurrent mucocutaneous herpes simplex virus infections, with a favourable response to ustekinumab. Through a review of reported cases of heterozygous variants in DSP SR6 (n = 15) and homozygous or compound heterozygous variants in DSG1 (n = 12) and SAM-like phenotype, we highlight phenotypic variability. Woolly hair, nail abnormalities and cardiomyopathy characterize patients with DSP variants, while elevated immunoglobulin E and food allergies are frequent in patients with DSG1 variants. Clinicians should be aware of the diverse manifestations of desmosomopathies.


Assuntos
Encefalopatias/genética , Dermatite Esfoliativa/genética , Desmoplaquinas/genética , Insuficiência de Crescimento/genética , Variação Genética , Herpes Simples/genética , Ictiose/genética , Encefalopatias/diagnóstico por imagem , Pré-Escolar , Dermatite Esfoliativa/diagnóstico , Dermatite Esfoliativa/tratamento farmacológico , Fármacos Dermatológicos/uso terapêutico , Insuficiência de Crescimento/diagnóstico , Predisposição Genética para Doença , Herpes Simples/diagnóstico , Herpes Simples/virologia , Humanos , Ictiose/diagnóstico , Ictiose/tratamento farmacológico , Lactente , Recém-Nascido , Masculino , Fenótipo , Índice de Gravidade de Doença , Resultado do Tratamento , Ustekinumab/uso terapêutico
11.
BMC Infect Dis ; 19(1): 382, 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31060582

RESUMO

BACKGROUND: Herpes simplex virus type-2 (HSV-2) infection is the main cause of genital ulcer disease and increases the risk of HIV acquisition. Little information is available regards the epidemiological characteristics of HSV-2 among general population in China. The aim of this study was to explore seroprevalence and associated factors of HSV-2 and provide information for design of HSV-2 control strategy in Shandong, China. METHODS: In this cross-sectional study, a total of 8074 persons, 18-49 years of age, were selected using multi-stage probability sampling to represent the general population of Shandong in 2016. Demographic data were collected through face-to-face interviews. Other variables were obtained by self-administered questionnaire surveys. Blood was collected for HSV-2 IgG detection with ELISA. RESULTS: A total of 7256 sexually-active participants were included in the analysis. The weighted seroprevalence of HSV-2 infection was 4.2% (95% confidence interval [CI], 3.2-5.3) in females, which was significant higher than that in males (2.7%; 95% CI, 1.1-4.2) (P = 0.04). The seroprevalence of HSV-2 was higher in individuals from eastern region (6.4%; 95% CI, 5.9-6.9) and urban areas (4.3%; 95% CI, 2.6-6.0) of Shandong than those from other regions (P < 0.01). Associated factors for HSV-2 infection among men were being urban residents (adjusted odds ratio [AOR], 2.36; 95% CI, 1.14-4.88), having two or more sex partners in the past year (AOR, 3.22; 95% CI, 1.90-5.43) and having commercial sex (AOR, 1.51; 95% CI, 1.00-2.26). Among females, being divorced or widowed (AOR, 1.79; 95% CI, 1.08-2.97), having a tattoo (AOR, 2.89; 95% CI, 1.07-7.84), and being dissatisfied with the sex activity quality (AOR, 2.12; 95% CI, 1.24-3.63) was associated with HSV-2 infection. CONCLUSIONS: This study showed a relatively low burden of HSV-2 in Shandong province, China compared with the seroprevalence reported in many other provinces and countries. HSV-2 control programs in Shandong should focus on eastern, urban and female residents, and pay more attention to individuals with identified associated factors.


Assuntos
Herpes Simples/diagnóstico , Adolescente , Adulto , China/epidemiologia , Estudos Transversais , Feminino , Herpes Simples/epidemiologia , Herpes Simples/virologia , Herpesvirus Humano 2/isolamento & purificação , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Soroepidemiológicos , Comportamento Sexual , Parceiros Sexuais , Inquéritos e Questionários , Adulto Jovem
13.
Dermatol Online J ; 25(4)2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-31046908

RESUMO

Darier disease (DD), also known as keratosis follicularis or Darier-White disease, is a rare autosomal dominant genodermatosis that presents as hyperkeratotic, warty papules affecting the seborrheic and intertriginous areas. Patients with DD are at risk of secondary infections including the rare complication of Kaposi varicelliform eruption (KVE), a widespread viral infection most commonly caused by herpes simplex virus (HSV). Darier disease with secondary KVE can lead to widespread systemic infection and death. This case report discusses an individual with DD who subsequently developed KVE due to disseminated HSV type 2 infection.


Assuntos
Doença de Darier/complicações , Herpes Simples/complicações , Herpes Simples/tratamento farmacológico , Herpesvirus Humano 1 , Herpesvirus Humano 2 , Erupção Variceliforme de Kaposi/etiologia , Aciclovir/uso terapêutico , Antivirais/uso terapêutico , Herpes Simples/virologia , Humanos , Masculino , Pessoa de Meia-Idade
14.
Elife ; 82019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-31090537

RESUMO

Viral infection is usually studied at the population level by averaging over millions of cells. However, infection at the single-cell level is highly heterogeneous, with most infected cells giving rise to no or few viral progeny while some cells produce thousands. Analysis of Herpes Simplex virus 1 (HSV-1) infection by population-averaged measurements has taught us a lot about the course of viral infection, but has also produced contradictory results, such as the concurrent activation and inhibition of type I interferon signaling during infection. Here, we combine live-cell imaging and single-cell RNA sequencing to characterize viral and host transcriptional heterogeneity during HSV-1 infection of primary human cells. We find extreme variability in the level of viral gene expression among individually infected cells and show that these cells cluster into transcriptionally distinct sub-populations. We find that anti-viral signaling is initiated in a rare group of abortively infected cells, while highly infected cells undergo cellular reprogramming to an embryonic-like transcriptional state. This reprogramming involves the recruitment of ß-catenin to the host nucleus and viral replication compartments, and is required for late viral gene expression and progeny production. These findings uncover the transcriptional differences in cells with variable infection outcomes and shed new light on the manipulation of host pathways by HSV-1.


Assuntos
Antivirais/metabolismo , Herpesvirus Humano 1/fisiologia , Análise de Célula Única , Animais , Ciclo Celular , Linhagem Celular , Núcleo Celular/metabolismo , Regulação Viral da Expressão Gênica , Herpes Simples/virologia , Humanos , Mutação/genética , Transdução de Sinais , Transcrição Genética , Replicação Viral , beta Catenina/metabolismo
15.
J Med Microbiol ; 68(5): 748-754, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30938666

RESUMO

PURPOSE: Herpes simplex virus (HSV) is a common lifelong sexually transmitted infection. HSV-1 typically manifests as oral cold sores, while HSV-2 is more traditionally associated with sexual transmission and infection. We have developed a real-time PCR (Trioplex) for the simultaneous detection of HSV-1 and -2 and the bacterial phage internal control (IC) MS2. METHODOLOGY: To determine the performance of the Trioplex method and resolve discrepancies, 178 clinical specimens from cutaneous and mucocutaneous sources were tested using 3 different methods; virus culture with direct fluorescent antibody (DFA) immunostaining, Trioplex and a commercially available HSV analyte-specific reagent (ASR). RESULTS: HSV Trioplex was significantly more sensitive than virus culture (89 and 67 % HSV 1/2, respectively) and comparable to the commercial assay (P<0.001). Cost analysis revealed that the Trioplex reduced cost by 80  % compared to cell culture. CONCLUSIONS: The implementation of the HSV Trioplex improved the detection turnaround time from 3-10 days to 2.5 h, thus streamlining Herpes detection, improving sensitivity and reducing laboratory costs.


Assuntos
Herpes Simples/diagnóstico , Herpesvirus Humano 1/genética , Herpesvirus Humano 2/genética , Reação em Cadeia da Polimerase em Tempo Real/economia , Pele/virologia , Custos e Análise de Custo , DNA Viral/análise , Feminino , Técnica Direta de Fluorescência para Anticorpo , Herpes Genital/diagnóstico , Herpes Genital/virologia , Herpes Simples/virologia , Herpesvirus Humano 1/isolamento & purificação , Herpesvirus Humano 2/isolamento & purificação , Humanos , Masculino , Reação em Cadeia da Polimerase em Tempo Real/métodos , Sensibilidade e Especificidade , Pele/patologia
16.
Braz J Microbiol ; 50(3): 663-668, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31001794

RESUMO

Polymorphisms in the structural gene MBL-2 (mannose-binding lectin-2) may result in low MBL serum concentration, associated with greater susceptibility to infection. The study evaluated the effects of MBL-2 polymorphisms with the oral manifestations of the HSV in human immunodeficiency virus (HIV)-infected patients. An observational case-control study was carried out, with the sample comprising 64 HIV+ and 65 healthy individuals. The signs and symptoms of HSV oral infection were evaluated, and oral mucosa buccal smears were collected. Polymorphisms of the MBL-2 gene and HSV-1 DNA were amplified through real-time PCR. The data revealed that of 64 HIV+, 29.6% presented signs and symptoms of HSV oral infection. Of these, the HSV-1 DNA was detected through real-time PCR in 21% of cases, and in 13.3% of asymptomatic individuals. There was no statistically significant difference between the symptomatic (p = 1) and the asymptomatic (p = 0.52) individuals, HIV+ and HIV-. Different genotypes (AA, A0, or 00) did not contribute to the oral manifestation of HSV in the HIV+ patients (p = 0.81) or HIV- (p = 0.45). There was no statistically significant difference in either group (p = 0.52). No significant association was identified between the MBL-2 gene polymorphisms in the oral manifestation of HSV infection. However, further studies are recommended with larger population groups before discarding this interrelationship.


Assuntos
Infecções por HIV/complicações , Herpes Simples/genética , Herpesvirus Humano 1/fisiologia , Lectina de Ligação a Manose/genética , Boca/virologia , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Infecções por HIV/genética , HIV-1/genética , HIV-1/isolamento & purificação , HIV-1/fisiologia , Herpes Simples/etiologia , Herpes Simples/virologia , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
17.
PLoS One ; 14(4): e0215487, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31009486

RESUMO

OBJECTIVES: To investigate the epidemiology of herpes simplex virus type 1 (HSV-1) in Latin America and the Caribbean. METHODS: Systematic review and meta-analytics guided by the Cochrane Collaboration Handbook and reported following the PRISMA guidelines. RESULTS: Thirty-three relevant reports were identified including 35 overall (and 95 stratified) seroprevalence measures, and five and nine proportions of virus isolation in genital ulcer disease (GUD) and in genital herpes, respectively. Pooled mean seroprevalence was 57.2% (95% CI: 49.7-64.6%) among children and 88.4% (95% CI: 85.2-91.2%) among adults. Pooled mean seroprevalence was lowest at 49.7% (95% CI: 42.8-56.6%) in those aged ≤10, followed by 77.8% (95% CI: 67.9-84.8%) in those aged 10-20, 82.8% (95% CI: 73.1-90.8%) in those aged 20-30, 92.5% (95% CI: 89.4-95.1%) in those aged 30-40, and 94.2% (95% CI: 92.7-95.5%) in those aged ≥40. Age was the strongest source of heterogeneity in seroprevalence, explaining 54% of variation. Evidence was found for seroprevalence decline over time. Pooled mean proportion of HSV-1 isolation was 0.9% (95% CI: 0.0-3.6%) in GUD and 10.9% (95% CI: 4.4-19.4%) in genital herpes. CONCLUSIONS: HSV-1 is a widely prevalent infection in this region, but its epidemiology may be slowly transitioning, with still limited contribution for HSV-1 in genital herpes.


Assuntos
Herpes Genital/epidemiologia , Herpes Simples/epidemiologia , Herpesvirus Humano 1/isolamento & purificação , Úlcera/epidemiologia , Região do Caribe/epidemiologia , Feminino , Herpes Genital/diagnóstico , Herpes Genital/virologia , Herpes Simples/diagnóstico , Herpes Simples/virologia , Herpesvirus Humano 1/fisiologia , Humanos , América Latina/epidemiologia , Masculino , Estudos Soroepidemiológicos , Úlcera/diagnóstico , Úlcera/virologia
18.
PLoS Pathog ; 15(4): e1007680, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30943264

RESUMO

Mediator of IRF3 activation (MITA, also known as STING and ERIS) is an essential adaptor protein for cytoplasmic DNA-triggered signaling and involved in innate immune responses, autoimmunity and tumorigenesis. The activity of MITA is critically regulated by ubiquitination and deubiquitination. Here, we report that USP49 interacts with and deubiquitinates MITA after HSV-1 infection, thereby turning down cellular antiviral responses. Knockdown or knockout of USP49 potentiated HSV-1-, cytoplasmic DNA- or cGAMP-induced production of type I interferons (IFNs) and proinflammatory cytokines and impairs HSV-1 replication. Consistently, Usp49-/- mice exhibit resistance to lethal HSV-1 infection and attenuated HSV-1 replication compared to Usp49+/+ mice. Mechanistically, USP49 removes K63-linked ubiquitin chains from MITA after HSV-1 infection which inhibits the aggregation of MITA and the subsequent recruitment of TBK1 to the signaling complex. These findings suggest a critical role of USP49 in terminating innate antiviral responses and provide insights into the complex regulatory mechanisms of MITA activation.


Assuntos
Herpes Simples/prevenção & controle , Imunidade Inata/imunologia , Lisina/metabolismo , Proteínas de Membrana/metabolismo , Ubiquitina Tiolesterase/metabolismo , Animais , Antivirais , Células HEK293 , Herpes Simples/imunologia , Herpes Simples/virologia , Herpesvirus Humano 1 , Humanos , Lisina/química , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transdução de Sinais , Células THP-1 , Ubiquitina Tiolesterase/genética , Ubiquitinação , Replicação Viral
19.
Transplant Proc ; 51(3): 993-997, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30979493

RESUMO

Recipients of organ transplants are immunosuppressed and at high risk of oral infection. Oral diseases are often neglected compared with infections of other organs that typically confer higher morbidity. However, severe local symptoms hinder oral intake, decrease quality of life, and are sometimes lethal. Here we describe a case of a 57-year-old woman who developed recurrent aphthous stomatitis after kidney transplantation; the cause of the infection was complex and included cytomegalovirus, herpes simplex virus, and Candida species. Since misdiagnosis of oral diseases impairs patient quality of life and increases morbidity, clinicians should be aware of possible etiologies of oral infections in renal transplant recipients.


Assuntos
Candida , Citomegalovirus , Transplante de Rim/efeitos adversos , Simplexvirus , Estomatite Aftosa/etiologia , Transplantados , Candidíase/complicações , Candidíase/microbiologia , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/virologia , Feminino , Herpes Simples/complicações , Herpes Simples/virologia , Humanos , Pessoa de Meia-Idade , Estomatite Aftosa/diagnóstico
20.
mSphere ; 4(1)2019 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-30814317

RESUMO

More than 14,000 neonates are infected with herpes simplex virus (HSV) annually. Approximately half display manifestations limited to the skin, eyes, or mouth (SEM disease). The rest develop invasive infections that spread to the central nervous system (CNS disease or encephalitis) or throughout the infected neonate (disseminated disease). Invasive HSV disease is associated with significant morbidity and mortality, but the viral and host factors that predispose neonates to these forms are unknown. To define viral diversity within the infected neonatal population, we evaluated 10 HSV-2 isolates from newborns with a range of clinical presentations. To assess viral fitness independently of host immune factors, we measured viral growth characteristics in cultured cells and found diverse in vitro phenotypes. Isolates from neonates with CNS disease were associated with larger plaque size and enhanced spread, with the isolates from cerebrospinal fluid (CSF) exhibiting the most robust growth. We sequenced complete viral genomes of all 10 neonatal viruses, providing new insights into HSV-2 genomic diversity in this clinical setting. We found extensive interhost and intrahost genomic diversity throughout the viral genome, including amino acid differences in more than 90% of the viral proteome. The genes encoding glycoprotein G (gG; US4), glycoprotein I (gI; US7), and glycoprotein K (gK; UL53) and viral proteins UL8, UL20, UL24, and US2 contained variants that were found in association with CNS isolates. Many of these viral proteins are known to contribute to cell spread and neurovirulence in mouse models of CNS disease. This report represents the first application of comparative pathogen genomics to neonatal HSV disease.IMPORTANCE Herpes simplex virus (HSV) causes invasive disease in half of infected neonates, resulting in significant mortality and permanent cognitive morbidity. The factors that contribute to invasive disease are not understood. This study revealed diversity among HSV isolates from infected neonates and detected the first associations between viral genetic variations and clinical disease manifestations. We found that viruses isolated from newborns with encephalitis showed enhanced spread in culture. These viruses contained protein-coding variations not found in viruses causing noninvasive disease. Many of these variations were found in proteins known to impact neurovirulence and viral spread between cells. This work advances our understanding of HSV diversity in the neonatal population and how it may impact disease outcome.


Assuntos
Variação Genética , Herpes Simples/virologia , Herpesvirus Humano 2/genética , Complicações Infecciosas na Gravidez/virologia , Linhagem Celular , Encefalite Viral/virologia , Feminino , Genoma Viral , Genômica , Genótipo , Idade Gestacional , Herpes Simples/complicações , Herpesvirus Humano 1/genética , Herpesvirus Humano 2/isolamento & purificação , Herpesvirus Humano 2/patogenicidade , Humanos , Recém-Nascido , Masculino , Fenótipo , Gravidez , Proteínas Virais/genética
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