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1.
Soft Matter ; 17(41): 9457-9468, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34612290

RESUMO

The possibility of contamination of human skin by infectious virions plays an important role in indirect transmission of respiratory viruses but little is known about the fundamental physico-chemical aspects of the virus-skin interactions. In the case of coronaviruses, the interaction with surfaces (including the skin surface) is mediated by their large glycoprotein spikes that protrude from (and cover) the viral envelope. Here, we perform all atomic simulations between the SARS-CoV-2 spike glycoprotein and human skin models. We consider an "oily" skin covered by sebum and a "clean" skin exposing the stratum corneum. The simulations show that the spike tries to maximize the contacts with stratum corneum lipids, particularly ceramides, with substantial hydrogen bonding. In the case of "oily" skin, the spike is able to retain its structure, orientation and hydration over sebum with little interaction with sebum components. Comparison of these results with our previous simulations of the interaction of SARS-CoV-2 spike with hydrophilic and hydrophobic solid surfaces, suggests that the "soft" or "hard" nature of the surface plays an essential role in the interaction of the spike protein with materials.


Assuntos
Ligação Proteica , Pele/virologia , Glicoproteína da Espícula de Coronavírus , COVID-19 , Humanos , Interações Hidrofóbicas e Hidrofílicas , Simulação de Dinâmica Molecular , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/metabolismo
2.
Sci Rep ; 11(1): 19817, 2021 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-34615949

RESUMO

Recent studies have focused their attention on conjunctivitis as one of the symptoms of coronavirus disease 2019 (COVID-19). Therefore, tear samples were taken from COVID-19 patients and the presence of SARS-CoV-2 was evidenced using Real Time reverse transcription polymerase chain reaction. The main aim of this study was to analyze mRNA expression in the tears of patients with COVID-19 compared with healthy subjects using Next Generation Sequencing (NGS). The functional evaluation of the transcriptome highlighted 25 genes that differ statistically between healthy individuals and patients affected by COVID-19. In particular, the NGS analysis identified the presence of several genes involved in B cell signaling and keratinization. In particular, the genes involved in B cell signaling were downregulated in the tears of COVID-19 patients, while those involved in keratinization were upregulated. The results indicated that SARS-CoV-2 may induce a process of ocular keratinization and a defective B cell response.


Assuntos
COVID-19/genética , Oftalmopatias/virologia , Lágrimas/metabolismo , Transcriptoma , Idoso , Linfócitos B/metabolismo , COVID-19/patologia , COVID-19/virologia , Oftalmopatias/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Queratinas/metabolismo , Masculino , SARS-CoV-2/isolamento & purificação , Análise de Sequência de RNA/métodos , Pele/metabolismo , Pele/patologia , Pele/virologia , Lágrimas/virologia
4.
Viruses ; 13(7)2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-34372563

RESUMO

The epidemiological role of domestic animals in the spread and transmission of SARS-CoV-2 to humans has been investigated in recent reports, but some aspects need to be further clarified. To date, only in rare cases have dogs and cats living with COVID-19 patients been found to harbour SARS-CoV-2, with no evidence of pet-to-human transmission. The aim of the present study was to verify whether dogs and cats act as passive mechanical carriers of SARS-CoV-2 when they live in close contact with COVID-19 patients. Cutaneous and interdigital swabs collected from 48 dogs and 15 cats owned by COVID-19 patients were tested for SARS-CoV-2 by qRT-PCR. The time elapsed between owner swab positivity and sample collection from pets ranged from 1 to 72 days, with a median time of 23 days for dogs and 39 days for cats. All samples tested negative, suggesting that pets do not passively carry SARS-CoV-2 on their hair and pads, and thus they likely do not play an important role in the virus transmission to humans. This data may contribute to confirming that the direct contact with the hair and pads of pets does not represent a route for the transmission of SARS-CoV-2.


Assuntos
COVID-19/veterinária , Doenças do Gato/virologia , Doenças do Cão/virologia , Cabelo/virologia , Animais de Estimação/virologia , SARS-CoV-2/isolamento & purificação , Pele/virologia , Animais , COVID-19/transmissão , Doenças do Gato/transmissão , Gatos , Doenças do Cão/transmissão , Cães , Humanos
5.
Indian J Pathol Microbiol ; 64(3): 532-534, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34341266

RESUMO

Background: Condylomata acuminata, commonly known as genital wart is a sexually transmitted disease caused by Human Papillomavirus (HPV). The positivity of HPV6/11 in condylomata acuminata in western literature varies from 80-90% however, there is a paucity of Indian literature. Aim: The aim of the present study was to determine the role of HPV 6 & 11 in Condylomata acuminata in Indian patients. Methods: A total of 22 formalin fixed parafilm embedded (FFPE) tissue was collected from the cases of condylomata acuminata which was histologically diagnosed and was used to detect HPV 6 and 11 by PCR. Results: Of these 14/22 patients (63.6%) were positive for HPV 6 or 11; HPV 6 alone in eight (36.3%) and HPV 11 in six (27.2%). Conclusion: The high HPV 6 and 11 PCR positivity suggests their definitive role in causation of condylomas cases. This important HPV infection is preventable by prophylactic vaccination.


Assuntos
Condiloma Acuminado/epidemiologia , Condiloma Acuminado/virologia , Papillomavirus Humano 6/patogenicidade , Papillomaviridae/patogenicidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Condiloma Acuminado/etnologia , DNA Viral , Feminino , Formaldeído , Papillomavirus Humano 6/genética , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Papillomaviridae/classificação , Papillomaviridae/genética , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Inclusão em Parafina , Pele/patologia , Pele/virologia , Adulto Jovem
6.
Biomed Res Int ; 2021: 5595016, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34258268

RESUMO

Background: COVID-19 is a pandemic disease worldwide. Although cutaneous manifestations may present in affected patients, there have been limited studies on the cutaneous findings and hair and nail abnormalities after discharge. Objective: To establish the cutaneous manifestations, hair and scalp disorders, and nail abnormalities in patients who recovered from COVID-19 infections. Methods: A retrospective chart review and telephone interviews were conducted to determine the cutaneous manifestations, hair and scalp disorders, and nail abnormalities of patients aged over 18 years who were diagnosed with COVID-19 infections at Siriraj Hospital, Bangkok, Thailand, between January and June 2020. Results: Ninety-three patients with prior COVID-19 infections participated in the study. The COVID-19 severity had been mild for most (71%). Cutaneous manifestations were reported in 8 patients (8.6%), with the common skin conditions being maculopapular rash and urticaria. The onsets of the skin conditions were before admission (1%), during admission (4.3%), and after discharge (3.2%). Increased hair shedding was also reported in 22 patients (23.7%), with a female predominance. Three patients were affected during admission, while the others were affected after discharge. The patients with moderate, severe, and critical COVID-19 infections experienced significantly more hair shedding than those with asymptomatic and mild diseases. Only 2 patients with mild COVID-19 disease reported nail abnormalities (chromonychia and brittle nails). Conclusions: Cutaneous manifestations, hair disorders, and nail abnormalities can occur in patients with COVID-19 after their discharge from hospital. Patients should therefore be followed up in anticipation of dermatological problems.


Assuntos
COVID-19 , Doenças do Cabelo , Doenças da Unha , Pandemias , SARS-CoV-2/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , COVID-19/metabolismo , Feminino , Seguimentos , Cabelo/metabolismo , Cabelo/virologia , Doenças do Cabelo/epidemiologia , Doenças do Cabelo/metabolismo , Doenças do Cabelo/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Doenças da Unha/epidemiologia , Doenças da Unha/metabolismo , Doenças da Unha/virologia , Unhas/metabolismo , Unhas/virologia , Pele/metabolismo , Pele/virologia
7.
Int J Mol Sci ; 22(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209998

RESUMO

Acne vulgaris, which is mostly associated with the colonization of Cutibacterium acnes (C. acnes), is a common skin inflammatory disease in teenagers. However, over the past few years, the disease has extended beyond childhood to chronically infect approximately 40% of adults. While antibiotics have been used for several decades to treat acne lesions, antibiotic resistance is a growing crisis; thus, finding a new therapeutic target is urgently needed. Studies have shown that phage therapy may be one alternative for treating multi-drug-resistant bacterial infections. In the present study, we successfully isolated a C. acnes phage named TCUCAP1 from the skin of healthy volunteers. Morphological analysis revealed that TCUCAP1 belongs to the family Siphoviridae with an icosahedral head and a non-contractile tail. Genome analysis found that TCUCAP1 is composed of 29,547 bp with a G+C content of 53.83% and 56 predicted open reading frames (ORFs). The ORFs were associated with phage structure, packing, host lysis, DNA metabolism, and additional functions. Phage treatments applied to mice with multi-drug-resistant (MDR) C.-acnes-induced skin inflammation resulted in a significant decrease in inflammatory lesions. In addition, our attempt to formulate the phage into hydroxyethyl cellulose (HEC) cream may provide new antibacterial preparations for human infections. Our results demonstrate that TCUCAP1 displays several features that make it an ideal candidate for the control of C. acnes infections.


Assuntos
Acne Vulgar/terapia , Terapia por Fagos/métodos , Propionibacterium acnes/virologia , Siphoviridae/classificação , Sequenciamento Completo do Genoma/métodos , Acne Vulgar/microbiologia , Animais , Composição de Bases , Celulose/química , Modelos Animais de Doenças , Composição de Medicamentos , Farmacorresistência Bacteriana Múltipla , Tamanho do Genoma , Genoma Viral , Voluntários Saudáveis , Humanos , Injeções Intradérmicas , Camundongos , Fases de Leitura Aberta , Filogenia , Propionibacterium acnes/fisiologia , Siphoviridae/genética , Siphoviridae/isolamento & purificação , Pele/virologia
8.
Molecules ; 26(14)2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34299596

RESUMO

Zika virus (ZIKV) represents a re-emerging threat to global health due to its association with congenital birth defects. ZIKV NS2B-NS3 protease is crucial for virus replication by cleaving viral polyprotein at various junctions to release viral proteins and cause cytotoxic effects in ZIKV-infected cells. This study characterized the inhibitory effects of doxycycline against ZIKV NS2B-NS3 protease and viral replication in human skin cells. The in silico data showed that doxycycline binds to the active site of ZIKV protease at a low docking energy (-7.8 Kcal/mol) via four hydrogen bonds with the protease residues TYR1130, SER1135, GLY1151, and ASP83. Doxycycline efficiently inhibited viral NS2B-NS3 protease at average human temperature (37 °C) and human temperature with a high fever during virus infection (40 °C). Interestingly, doxycycline showed a higher inhibitory effect at 40 °C (IC50 = 5.3 µM) compared to 37 °C (9.9 µM). The virus replication was considerably reduced by increasing the concentration of doxycycline. An approximately 50% reduction in virus replication was observed at 20 µM of doxycycline. Treatment with 20 µM of doxycycline reduced the cytopathic effects (CPE), and the 40 µM of doxycycline almost eliminated the CPE of human skin cells. This study showed that doxycycline binds to the ZIKV protease and inhibits its catalytic activity at a low micro-molecular concentration range. Treatment of human skin fibroblast with doxycycline eliminated ZIKV infection and protected the cells against the cytopathic effects of the infection.


Assuntos
Doxiciclina/farmacologia , Fibroblastos/metabolismo , Pele/metabolismo , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas Virais/antagonistas & inibidores , Replicação Viral/efeitos dos fármacos , Zika virus/fisiologia , Animais , Chlorocebus aethiops , Doxiciclina/química , Fibroblastos/virologia , Humanos , Serina Endopeptidases/química , Serina Endopeptidases/metabolismo , Pele/virologia , Células Vero , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/metabolismo , Proteínas Virais/química , Proteínas Virais/metabolismo , Zika virus/química
9.
Biomolecules ; 11(6)2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-34200112

RESUMO

The SARS-CoV-2 pandemic has dramatically changed our lives and habits. In just a few months, the most advanced and efficient health systems in the world have been overwhelmed by an infectious disease that has caused 3.26 million deaths and more than 156 million cases worldwide. Although the lung is the most frequently affected organ, the skin has also resulted in being a target body district, so much so as to suggest it may be a real "sentinel" of COVID-19 disease. Here we present 17 cases of skin manifestations studied and analyzed in recent months in our Department; immunohistochemical investigations were carried out on samples for the S1 spike-protein of SARS-CoV-2, as well as electron microscopy investigations showing evidence of virions within the constituent cells of the eccrine sweat glands and the endothelium of small blood vessels. Finally, we conduct a brief review of the COVID-related skin manifestations, confirmed by immunohistochemistry and/or electron microscopy, described in the literature.


Assuntos
COVID-19/patologia , SARS-CoV-2/isolamento & purificação , Dermatopatias/virologia , Pele/patologia , Adolescente , Adulto , COVID-19/diagnóstico , COVID-19/virologia , Criança , Eritema/diagnóstico , Eritema/patologia , Eritema/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/fisiologia , Pele/virologia , Dermatopatias/diagnóstico , Dermatopatias/patologia , Adulto Jovem
10.
Arch Virol ; 166(9): 2603-2606, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34115213

RESUMO

A novel papillomavirus (PV) was detected in farmed wels catfish (Silurus glanis) in Hungary showing clinical signs resembling those of wels catfish herpesvirus disease. The whole genome of Silurus glanis papillomavirus 1 (SgPV1) was identified using next-generation sequencing. The 5,612-bp complete genome contains four predicted protein coding regions (E1, E2, L1, and L2), which seem to have homologues in every PV genome sequenced to date. Five complete fish PV genome sequences are available in the GenBank database. Their genomes range between 5,748 and 6,086 bp and contain the minimal PV backbone genes E1, E2, L2, and L1, unlike PVs of higher vertebrates, which have larger genomes (6.8-8.6 kbp) and additional (onco)genes. Considering the current species demarcation criteria for the family Papillomaviridae, the establishment of a novel species named "Nunpapillomavirus siluri" is proposed for the SgPV1 in a novel genus, "Nunpapillomavirus", in the subfamily Secondpapillomavirinae.


Assuntos
Peixes-Gato/virologia , Doenças dos Peixes/virologia , Papillomaviridae/classificação , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/veterinária , Infecções por Papillomavirus/virologia , Sequenciamento Completo do Genoma , Animais , Genoma Viral , Sequenciamento de Nucleotídeos em Larga Escala , Hungria , Fases de Leitura Aberta , Filogenia , Pele/virologia
11.
Arch Virol ; 166(9): 2569-2572, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34115212

RESUMO

Human papillomaviruses (HPVs) cause superficial epidermal infections and are only cleared if they trigger an immunological response. We analysed SNPs that had previously been investigated for association with HPV infection to determine whether they play a role in the serological response to cutaneous beta-HPVs in an Australian population. Serum samples from 1,142 participants were analysed for seropositivity against the L1 protein of 21 beta-HPV types. Associations between seropositivity to beta-HPV types and the SNPs rs9264942 (HLA-C; HPV-9, p = 0.022, HPV-15, p = 0.043 and HPV-17, p = 0.004), rs12449858 (EVER1; HPV-23, p = 0.029), and rs2981451 (FGFR2; HPV-22, p = 0.049) were identified. We found that certain SNPs could be involved in the serological response to beta-HPVs.


Assuntos
Alphapapillomavirus/genética , Papillomaviridae/genética , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Polimorfismo de Nucleotídeo Único , Testes Sorológicos , Adulto , Idoso , Austrália , Feminino , Genes Virais/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Pele/virologia
12.
Int J Mol Sci ; 22(10)2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065594

RESUMO

Advances in virology and skin cancer over recent decades have produced achievements that have been recognized not only in the field of dermatology, but also in other areas of medicine. They have modified the therapeutic and preventive solutions that can be offered to some patients and represent a significant step forward in our knowledge of the biology of skin cancer. In this paper, we review the viral agents responsible for different types of skin cancer, especially for solid skin tumors. We focus on human papillomavirus and squamous cell cancers, Merkel cell polyomavirus and Merkel cell carcinoma, and human herpesvirus 8 and Kaposi's sarcoma.


Assuntos
Neoplasias Cutâneas/virologia , Vírus/patogenicidade , Animais , DNA Viral/genética , Humanos , Pele/virologia , Vírus/genética
13.
Am J Clin Dermatol ; 22(4): 523-540, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34008162

RESUMO

Viral venereal diseases remain difficult to treat. Human papilloma virus (HPV) and herpes simplex virus (HSV) are two common viral venereal diseases. HPV infections are characterized by anogenital warts and less commonly by premalignant or malignant lesions. HSV infections classically present as grouped vesicles on an erythematous base with associated burning or pain; however, immunosuppressed patients may have atypical presentations with nodular or ulcerative lesions. This review discusses the epidemiology, diagnosis, and management of anogenital HPV and HSV infections with an emphasis on treatment modalities for the practicing dermatologist. Diagnosis of these diseases typically relies on clinical assessment, although multiple diagnostic techniques can be utilized and are recommended when diagnosis is uncertain or evaluating an individual with increased risk of malignancy. Management of HPV and HSV infections involves appropriate counseling, screening, and multiple treatment techniques. Particularly for HPV infections, a practitioner may need to use a combination of techniques to achieve the desired outcome.


Assuntos
Infecções por Herpesviridae/diagnóstico , Infecções por Papillomavirus/diagnóstico , Doenças Virais Sexualmente Transmissíveis/diagnóstico , Dermatopatias Virais/diagnóstico , Alphapapillomavirus/isolamento & purificação , Terapia Combinada/métodos , Terapia Combinada/normas , Aconselhamento/normas , Dermatologia/métodos , Dermatologia/normas , Herpesviridae/isolamento & purificação , Infecções por Herpesviridae/epidemiologia , Infecções por Herpesviridae/terapia , Infecções por Herpesviridae/transmissão , Humanos , Programas de Rastreamento/normas , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/terapia , Infecções por Papillomavirus/transmissão , Guias de Prática Clínica como Assunto , Prevalência , Fatores de Risco , Doenças Virais Sexualmente Transmissíveis/epidemiologia , Doenças Virais Sexualmente Transmissíveis/terapia , Doenças Virais Sexualmente Transmissíveis/transmissão , Pele/patologia , Pele/virologia , Dermatopatias Virais/epidemiologia , Dermatopatias Virais/terapia , Dermatopatias Virais/transmissão
14.
BMC Infect Dis ; 21(1): 501, 2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34051756

RESUMO

BACKGROUND: Tick-borne pathogens other than Borrelia burgdorferi sensu lato - the causative agent of Lyme borreliosis - are common in Ixodes ricinus ticks. How often these pathogens cause human disease is unknown. In addition, diagnostic tools to identify such diseases are lacking or reserved to research laboratories. To elucidate their prevalence and disease burden, the study 'Ticking on Pandora's Box' has been initiated, a collaborative effort between Amsterdam University Medical Center and the National Institute for Public Health and the Environment. METHODS: The study investigates how often the tick-borne pathogens Anaplasma phagocytophilum, Babesia species, Borrelia miyamotoi, Neoehrlichia mikurensis, spotted fever group Rickettsia species and/or tick-borne encephalitis virus cause an acute febrile illness after tick-bite. We aim to determine the impact and severity of these tick-borne diseases in the Netherlands by measuring their prevalence and describing their clinical picture and course of disease. The study is designed as a prospective case-control study. We aim to include 150 cases - individuals clinically suspected of a tick-borne disease - and 3 matched healthy control groups of 200 persons each. The controls consist respectively of a group of individuals with either a tick-bite without complaints, the general population and of healthy blood donors. During a one-year follow-up we will acquire blood, urine and skin biopsy samples and ticks at baseline, 4 and 12 weeks. Additionally, participants answer modified versions of validated questionnaires to assess self-reported symptoms, among which the SF-36, on a 3 monthly basis. DISCUSSION: This article describes the background and design of the study protocol of 'Ticking on Pandora's Box'. With our study we hope to provide insight into the prevalence, clinical presentation and disease burden of the tick-borne diseases anaplasmosis, babesiosis, B. miyamotoi disease, neoehrlichiosis, rickettsiosis and tick-borne encephalitis and to assist in test development as well as provide recommendations for national guidelines. TRIAL REGISTRATION: NL9258 (retrospectively registered at Netherlands Trial Register, trialregister.nl in in February 2021).


Assuntos
Ixodes/microbiologia , Doenças Transmitidas por Carrapatos/epidemiologia , Doenças Transmitidas por Carrapatos/microbiologia , Adulto , Animais , Sangue/microbiologia , Sangue/virologia , Estudos de Casos e Controles , DNA Bacteriano , Febre/epidemiologia , Febre/microbiologia , Febre/virologia , Seguimentos , Humanos , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Prevalência , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , Índice de Gravidade de Doença , Pele/microbiologia , Pele/virologia , Inquéritos e Questionários , Picadas de Carrapatos/epidemiologia , Picadas de Carrapatos/microbiologia , Picadas de Carrapatos/virologia , Urina/microbiologia , Urina/virologia
15.
Nat Commun ; 12(1): 2936, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-34006861

RESUMO

Host protection against cutaneous herpes simplex virus 1 (HSV-1) infection relies on the induction of a robust adaptive immune response. Here, we show that Nav1.8+ sensory neurons, which are involved in pain perception, control the magnitude of CD8 T cell priming and expansion in HSV-1-infected mice. The ablation of Nav1.8-expressing sensory neurons is associated with extensive skin lesions characterized by enhanced inflammatory cytokine and chemokine production. Mechanistically, Nav1.8+ sensory neurons are required for the downregulation of neutrophil infiltration in the skin after viral clearance to limit the severity of tissue damage and restore skin homeostasis, as well as for eliciting robust CD8 T cell priming in skin-draining lymph nodes by controlling dendritic cell responses. Collectively, our data reveal an important role for the sensory nervous system in regulating both innate and adaptive immune responses to viral infection, thereby opening up possibilities for new therapeutic strategies.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Herpes Simples/imunologia , Herpesvirus Humano 1/imunologia , Dor Nociceptiva/imunologia , Células Receptoras Sensoriais/imunologia , Animais , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/virologia , Citocinas/imunologia , Citocinas/metabolismo , Feminino , Herpes Simples/genética , Herpes Simples/virologia , Herpesvirus Humano 1/fisiologia , Humanos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Canal de Sódio Disparado por Voltagem NAV1.8/genética , Canal de Sódio Disparado por Voltagem NAV1.8/imunologia , Canal de Sódio Disparado por Voltagem NAV1.8/metabolismo , Infiltração de Neutrófilos/imunologia , Dor Nociceptiva/genética , Dor Nociceptiva/metabolismo , Células Receptoras Sensoriais/metabolismo , Células Receptoras Sensoriais/virologia , Pele/imunologia , Pele/metabolismo , Pele/virologia
16.
Immunology ; 164(2): 279-291, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34003499

RESUMO

Cytomegalovirus (CMV) induction of large frequencies of highly functional memory T cells has attracted much interest in the utility of CMV-based vaccine vectors, with exciting preclinical data obtained in models of infectious diseases and cancer. However, pathogenesis of human CMV (HCMV) remains a concern. Attenuated CMV-based vectors, such as replication- or spread-deficient viruses, potentially offer an alternative to fully replicating vectors. However, it is not well understood how CMV attenuation impacts vector immunogenicity, particularly when administered via relevant routes of immunization such as the skin. Herein, we used the murine cytomegalovirus (MCMV) model to investigate the impact of vector attenuation on T-cell memory formation following subcutaneous administration. We found that the spread-deficient virus (ΔgL-MCMV) was impaired in its ability to induce memory CD8+ T cells reactive to some (M38, IE1) but not all (IE3) viral antigens. Impaired-memory T-cell development was associated with a preferential and pronounced loss of polyfunctional (IFN-γ+ TNF-α+ ) T cells and also reduced accumulation of TCF1+ T cells, and was not rescued by increasing the dose of replication-defective MCMV. Finally, whilst vector attenuation reduced dendritic cell (DC) recruitment to skin-draining lymph nodes, systematic depletion of multiple DC subsets during acute subcutaneous MCMV infection had a negligible impact on T-cell memory formation, implying that attenuated responses induced by replication-deficient vectors were likely not a consequence of impaired initial DC activation. Thus, overall, these data imply that the choice of antigen and/or cloning strategy of exogenous antigen in combination with the route of immunization may influence the ability of attenuated CMV vectors to induce robust functional T-cell memory.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Infecções por Citomegalovirus/imunologia , Citomegalovirus/imunologia , Células Dendríticas/imunologia , Memória Imunológica/imunologia , Pele/imunologia , Replicação Viral/imunologia , Animais , Antígenos Virais/imunologia , Linfócitos T CD8-Positivos/virologia , Infecções por Citomegalovirus/virologia , Células Dendríticas/virologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Pele/virologia
17.
Säo Paulo med. j ; 139(2): 186-189, Mar.-Apr. 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1181004

RESUMO

ABSTRACT CONTEXT: Various skin manifestations have been reported in coronavirus disease. It may be difficult to determine the etiology of these lesions in view of the increased frequency of handwashing during the pandemic, along with occurrences of irritant contact dermatitis and allergic contact dermatitis due to disinfectant use; usage of herbal medicine and supplements to strengthen the immune system; and urticarial or maculopapular drug eruptions due to COVID-19 treatment. The variety of associated skin manifestations seen with COVID-19 makes it challenging to identify virus-specific skin manifestations. Petechiae, purpura, acrocyanosis and necrotic and non-necrotic purpura, which can be considered as manifestations of vascular involvement on the skin, have been reported. CASE REPORT: Here, we report a case of eruptive cherry angiomas, which was thought to have developed due to COVID-19, with a papulovesicular rash on distal extremities that progressed over time to reticular purpura. CONCLUSION: The case presented had a papulovesicular rash at the onset, which evolved to retiform purpura, and eruptive cherry angiomas were observed. It should be kept in mind that dermatological signs may vary in patients with COVID-19.


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Púrpura/virologia , Pele/virologia , Dermatopatias Virais/virologia , Exantema/virologia , COVID-19/complicações , COVID-19/virologia , Hemangioma/virologia , Pele/efeitos dos fármacos , Pele/patologia , Resultado do Tratamento , Dermatopatias Virais/diagnóstico , Dermatopatias Virais/terapia , Teste para COVID-19 , SARS-CoV-2 , COVID-19/tratamento farmacológico , COVID-19/terapia
18.
Clin Microbiol Infect ; 27(7): 1042.e1-1042.e4, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33901670

RESUMO

OBJECTIVES: Disinfection effectiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on human skin remains unclear because of the hazards of viral exposure. An evaluation model, which has been previously generated using human skin obtained from forensic autopsy samples, accurately mimics in vivo skin conditions for evaluating the effectiveness of disinfection against the virus. Using this model, we evaluated disinfection effectiveness against viruses on human skin. METHODS: Ethanol (EA), isopropanol (IPA), chlorhexidine gluconate (CHG) and benzalkonium chloride (BAC) were used as target disinfectants. First, disinfectant effectiveness against SARS-CoV-2 and influenza A virus (IAV) was evaluated in vitro. Disinfectant effectiveness against SARS-CoV-2 and IAV on human skin was then evaluated by titrating viruses present on the skin after applying each disinfectant on the skin for 5-60 seconds. RESULTS: Both, SARS-CoV-2 and IAV on human skin were completely inactivated within 5 seconds by 40%-80% EA and 70% IPA (log reduction values (LRVs) were >4). However, SARS-CoV-2 and IAV were barely inactivated by 20% EA (LRVs were <1). In vitro evaluation showed that, compared with EA and IPA, CHG and BAC were significantly inferior in terms of disinfection effectiveness. Conversely, the disinfection effectiveness of CHG and BAC against SARS-CoV-2 was higher on human skin than in vitro, and increased with increases in their concentration and reaction time (LRVs of 0.2% CHG/0.05% BAC were >2, and LRVs of 1.0% CHG/0.2% BAC were >2.5). CONCLUSIONS: Proper hand hygiene practices using alcohol-based disinfectants such as EA/IPA effectively inactivate SARS-CoV-2 and IAV on human skin.


Assuntos
COVID-19/prevenção & controle , Desinfetantes/farmacologia , Vírus da Influenza A/efeitos dos fármacos , Influenza Humana/prevenção & controle , SARS-CoV-2/efeitos dos fármacos , 2-Propanol/farmacologia , Anti-Infecciosos Locais/farmacologia , Compostos de Benzalcônio/farmacologia , COVID-19/virologia , Clorexidina/análogos & derivados , Clorexidina/farmacologia , Etanol/farmacologia , Higiene das Mãos/métodos , Humanos , Modelos Biológicos , Pele/virologia
19.
Front Immunol ; 12: 625993, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33643313

RESUMO

Ticks and tick transmitted infectious agents are increasing global public health threats due to increasing abundance, expanding geographic ranges of vectors and pathogens, and emerging tick-borne infectious agents. Greater understanding of tick, host, and pathogen interactions will contribute to development of novel tick control and disease prevention strategies. Tick-borne pathogens adapt in multiple ways to very different tick and vertebrate host environments and defenses. Ticks effectively pharmacomodulate by its saliva host innate and adaptive immune defenses. In this review, we examine the idea that successful synergy between tick and tick-borne pathogen results in host immune tolerance that facilitates successful tick infection and feeding, creates a favorable site for pathogen introduction, modulates cutaneous and systemic immune defenses to establish infection, and contributes to successful long-term infection. Tick, host, and pathogen elements examined here include interaction of tick innate immunity and microbiome with tick-borne pathogens; tick modulation of host cutaneous defenses prior to pathogen transmission; how tick and pathogen target vertebrate host defenses that lead to different modes of interaction and host infection status (reservoir, incompetent, resistant, clinically ill); tick saliva bioactive molecules as important factors in determining those pathogens for which the tick is a competent vector; and, the need for translational studies to advance this field of study. Gaps in our understanding of these relationships are identified, that if successfully addressed, can advance the development of strategies to successfully disrupt both tick feeding and pathogen transmission.


Assuntos
Imunidade Adaptativa , Tolerância Imunológica , Imunidade Inata , Glândulas Salivares/imunologia , Pele/imunologia , Picadas de Carrapatos/imunologia , Doenças Transmitidas por Carrapatos/imunologia , Carrapatos/imunologia , Animais , Interações Hospedeiro-Patógeno , Humanos , Glândulas Salivares/microbiologia , Glândulas Salivares/virologia , Pele/microbiologia , Pele/virologia , Picadas de Carrapatos/microbiologia , Picadas de Carrapatos/virologia , Doenças Transmitidas por Carrapatos/microbiologia , Doenças Transmitidas por Carrapatos/transmissão , Doenças Transmitidas por Carrapatos/virologia , Carrapatos/microbiologia , Carrapatos/virologia
20.
J Clin Invest ; 131(9)2021 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-33784252

RESUMO

Tissue-based T cells are important effectors in the prevention and control of mucosal viral infections; less is known about tissue-based B cells. We demonstrate that B cells and antibody-secreting cells (ASCs) are present in inflammatory infiltrates in skin biopsy specimens from study participants during symptomatic herpes simplex virus 2 (HSV-2) reactivation and early healing. Both CD20+ B cells, most of which are antigen inexperienced based on their coexpression of IgD, and ASCs - characterized by dense IgG RNA expression in combination with CD138, IRF4, and Blimp-1 RNA - were found to colocalize with T cells. ASCs clustered with CD4+ T cells, suggesting the potential for crosstalk. HSV-2-specific antibodies to virus surface antigens were also present in tissue and increased in concentration during HSV-2 reactivation and healing, unlike in serum, where concentrations remained static over time. B cells, ASCs, and HSV-specific antibody were rarely detected in biopsies of unaffected skin. Evaluation of samples from serial biopsies demonstrated that B cells and ASCs followed a more migratory than resident pattern of infiltration in HSV-affected genital skin, in contrast to T cells. Together, these observations suggest the presence of distinct phenotypes of B cells in HSV-affected tissue; dissecting their role in reactivation may reveal new therapeutic avenues to control these infections.


Assuntos
Anticorpos Antivirais/imunologia , Linfócitos B/imunologia , Herpes Simples/imunologia , Herpesvirus Humano 2/fisiologia , Imunoglobulina D/imunologia , Imunoglobulina G/imunologia , Pele/imunologia , Ativação Viral/imunologia , Adulto , Linfócitos B/patologia , Linfócitos T CD4-Positivos , Feminino , Herpes Simples/patologia , Humanos , Masculino , Pele/patologia , Pele/virologia
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