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1.
Sex Transm Infect ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914476

RESUMO

OBJECTIVES: The 2022 global outbreak of monkeypox virus (MPXV), previously confined to Central and West Africa, necessitates an enhanced understanding of its spread. Comprehensive genomic surveillance to understand the virus's evolution and spread is needed, particularly in Asia. METHODS: Genomic data from 169 MPXV genome sequences in Asia were analysed. Through advanced genomic sequencing of clinical samples, we analysed the distribution and mutations of MPXV lineages in Asia. RESULTS: Phylogenetic analysis revealed a distinct clustering of C.1 strains rise in Northeast Asia in 2023, while genomic examination identified specific consensus mutations like R84K, R665C and L16F in C.1 strains. The mutations, coupled with an increased rate of apolipoprotein B mRNA-editing catalytic polypeptide-like 3 motif G-to-A mutations in C.1 (OR 24.87±8.81), indicate a potential adaptation mechanism. CONCLUSIONS: Our findings underscore the need for ongoing surveillance and provide vital insights into MPXV's evolving dynamics, aiding in public health strategy formulation against this emerging infectious threat.

2.
Pathogens ; 13(6)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38921737

RESUMO

CRISPR-Cas systems are adaptive immune mechanisms present in most prokaryotes that play an important role in the adaptation of bacteria and archaea to new environments. Shewanella algae is a marine zoonotic pathogen with worldwide distribution, which accounts for the majority of clinical cases of Shewanella infections. However, the characterization of Shewanella algae CRISPR-Cas systems has not been well investigated yet. Through whole genome sequence analysis, we characterized the CRISPR-Cas systems in S. algae. Our results indicate that CRISPR-Cas systems are prevalent in S. algae, with the majority of strains containing the Type I-F system. This study provides new insights into the diversity and function of CRISPR-Cas systems in S. algae and highlights their potential role in the adaptation and survival of these marine pathogens.

3.
J Fungi (Basel) ; 9(9)2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37755040

RESUMO

Concurrent infections caused by multiple fungal pathogens in immunocompromised patients can pose diagnostic and treatment challenges. Here, we presented the first reported case in Taiwan of an AIDS patient who had concurrent infection with Cryptococcus neoformans meningitis and Talaromyces amestolkiae lymphadenopathy. The patient presented with an enlarged inguinal lymph node and was diagnosed with T. amestolkiae lymphadenitis. The species T. amestolkiae was identified using DNA sequencing, which had the capability of differentiating it from other Talaromyces species. The patient was discharged from the hospital following treatment with amphotericin B and subsequent administration of voriconazole. This case highlights the importance of maintaining a suspicion of co-infections and utilizing appropriate diagnostic tools, such as DNA sequencing, to identify possible pathogens. Further studies are needed to determine the optimal treatment for T. amestolkiae and other co-infecting fungal pathogens.

4.
Int J STD AIDS ; 34(10): 740-744, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37147923

RESUMO

To date, the identification of crypotococcal relapse remains clinically challenging as it often has similar manifestation with paradoxical immune reconstitution inflammatory syndrome. This study reports on the use of metagenomics assisted next generation sequencing to aid in diagnosing recurrent cryptococcal meningitis in an person living with HIV experiencing recurring symptoms, despite negative culture results for Cryptococcus neoformans in the cerebrospinal fluid. Although fungal culture was negative, when reads from metagenomic and metatranscriptomic sequencing performed on the Day 308 cerebrospinal fluid sample were mapped onto the genome from the Day 4 isolate, 589 specific reads were identified. NCBI BLAST search also revealed Cryptococcus-specific 18S/25S/28S ribosomal RNA, indicating a relapse of the disease.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS , Cryptococcus neoformans , Infecções por HIV , Meningite Criptocócica , Humanos , Meningite Criptocócica/diagnóstico , Meningite Criptocócica/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Metagenômica , Cryptococcus neoformans/genética , Recidiva , Infecções por HIV/complicações
5.
Antibiotics (Basel) ; 12(4)2023 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-37107111

RESUMO

The emergence of carbapenem-resistant Klebsiella pneumoniae poses a significant threat to public health. In this study, we aimed to investigate the distribution and genetic diversity of plasmids carrying beta-lactamase resistance determinants in a collection of carbapenem-resistant K. pneumoniae blood isolates. Blood isolates of carbapenem-resistant K. pneumoniae bacteremia were collected and identified. Whole-genome sequencing, assembly and analysis were performed for the prediction of antimicrobial resistance determinants. Plasmidome analysis was also performed. Our plasmidome analysis revealed two major plasmid groups, IncFII/IncR and IncC, as key players in the dissemination of carbapenem resistance among carbapenem-resistant K. pneumoniae. Notably, plasmids within the same group exhibited conservation of encapsulated genes, suggesting that these plasmid groups may serve as conservative carriers of carbapenem-resistant determinants. Additionally, we investigated the evolution and expansion of IS26 integrons in carbapenem-resistant K. pneumoniae isolates using long-read sequencing. Our findings revealed the evolution and expansion of IS26 structure, which may have contributed to the development of carbapenem resistance in these strains. Our findings indicate that IncC group plasmids are associated with the endemic occurrence of carbapenem-resistant K. pneumoniae, highlighting the need for targeted interventions to control its spread. Although our study focuses on the endemic presence of carbapenem-resistant K. pneumoniae, it is important to note that carbapenem-resistant K. pneumoniae is indeed a global problem, with cases reported in multiple regions worldwide. Further research is necessary to better understand the factors driving the worldwide dissemination of carbapenem-resistant K. pneumoniae and to develop effective strategies for its prevention and control.

6.
Mar Pollut Bull ; 191: 114933, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37119586

RESUMO

Marine debris is a vital issue in ocean governance. While education outreach can promote individual learning and develop pro-environmental behavior, research on marine debris education remains scarce. Kolb's experiential learning theory may provide a holistic model for marine debris education; therefore, this study developed an experiential-learning based marine debris (ELBMD) beach cleanup curriculum and analyzed the participants' performance during Kolb's four-stage cycle. The results revealed that (1) the ELBMD curriculum deepened the participants' understanding of marine debris, created a sense of responsibility, and increased their confidence in analytical skills and intention to act responsibly. (2) Reflection (Stage II) encouraged participants to think deeply about the human-environment relationship, which induced pro-environmental behavior and awareness of political engagement (Stage IV). (3) Peer discussion (Stage III) induced participants to refine their conception architecture, form values, and practice pro-environmental behavior (Stage IV). The results may aid the development of future marine debris education.


Assuntos
Currículo , Aprendizagem Baseada em Problemas , Humanos , Aprendizagem Baseada em Problemas/métodos
7.
Infect Drug Resist ; 16: 661-675, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36743336

RESUMO

Respiratory syncytial virus (RSV) is one of the most common respiratory viruses. It not only affects young children but also the elderly and immunocompromised patients. After the emergence of SARS-CoV-2 and the corona virus disease 2019 (COVID-19) era, a dramatic reduction in RSV activity was found, which coincided with the implementation of public health and social measures (PHSMs). However, the correlation is more complicated than we initially thought. After PHSMs were gradually lifted, a seasonality shift and a delayed RSV outbreak with greater number of infected patients were found in numerous countries, such as Israel, Australia, South Africa, New Zealand, France, United States, and Japan. Several hypotheses and possible reasons explaining the interaction between SARS-CoV-2 and RSV were mentioned. Since RSV vaccinations are still under investigation, administration of palivizumab should be considered in high-risk patients. In the post-COVID-19 era, greater attention should be paid to a further resurgence of RSV. In this narrative review, we conducted a thorough review of the current knowledge on the epidemiology of RSV during the COVID-19 era, the out-of-season outbreak of RSV, and the data on co-infection with RSV and SARS-CoV-2.

8.
Artigo em Inglês | MEDLINE | ID: mdl-36768042

RESUMO

When considering how to improve public literacy and behavior related to specific themes, top priority is usually given to strategies that enhance relevant knowledge. Fostering attitude comes later. Understanding the mechanisms of behavior may help us develop better policy and educational strategies. However, how knowledge and attitude impact behavior is still under investigation. The aim of this study is to explore the relationships among ocean knowledge, attitude toward the ocean, and the intention to behave responsibly in the marine setting. Specifically, we investigated a potential mediation mechanism by recruiting a total of 266 participants, whose ocean knowledge, attitudes toward the ocean, and intention to behave responsibly were evaluated using questionnaires. The results indicate that a person's attitude toward the ocean may indeed be a mediating factor between ocean knowledge and their intention to show positive marine behavior. In order to engage people in responsible ocean behavior, other forms of assistance from marine policy and education are recommended. Additionally, it would be of interest for future studies to investigate the effects of attitude and attitude-related knowledge in the development of ocean actions.


Assuntos
Atitude , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Intenção , Inquéritos e Questionários , Escolaridade , Oceanos e Mares
9.
Int J Gen Med ; 16: 317-327, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36718144

RESUMO

Infective endocarditis is a potentially fatal condition, and identifying the pathogen is crucial to optimizing antibiotic treatment. While a blood culture takes time and may yield negative results, it remains the gold standard for diagnosis, blood culture-negative endocarditis, which accounts for up to 20% of infective endocarditis cases, poses a clinical challenge with increasing mortality. To better understand the etiology of blood culture-negative infective endocarditis, we reviewed non-culture-based strategies and compared the results. Serology tests work best in limited pathogens, such as Coxiella burnetii and Bartonella infections. Most of the pathogens identified by broad-range PCR tests are Streptococcus spp, Staphylococcus spp and Propionibacterium spp. adding specific real-time PCR assays to the systematic PCR testing of patients with blood culture-negative endocarditis will increase the efficiency of diagnosis. Recently, metagenomic next-generation sequencing has also shown promising results.

10.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-971366

RESUMO

OBJECTIVES@#Cervical squamous cell carcinoma is the most common cancer in female reproductive system. This study aims to explore the effect of microRNA-9-5p (miR-9-5p) on the migration, invasion, and epithelial-mesenchymal transition (EMT) process of cervical squamous cells.@*METHODS@#Bioinformatics were used to predict the miRNAs that could bind to E-cadherin (E-cad). The Cancer Genome Atlas (TCGA) database was used to analyze and extract significantly differentially expressed miRNAs from part of cervical squamous cell carcinoma tissues and normal cervical tissues, and miR-9-5p was selected as the main research target. The translated regions (UTR) of wild-type E-cad (E-cad-WT 3'-UTR) or the 3'-UTR of mutant E-cad (E-Cad-MUT 3'-UTR) was transfected with miR-9-5p mimic normal control (NC), and miR-9-5p mimic was co-transfected human embryonic kidney cells (293T). The relationship between miR-9-5p and E-cad was detected by double luciferase assay. The expression of miR-9-5p in normal cervical epithelial cell lines (H8) and cervical squamous cell lines (C33A, siha, caski and Me180) were detected by quantitative real-time PCR. Then, the experiments were divided into groups as follows: a block control group, an overexpression control group (mimic-NC group), a miR-95p overexpression group (mimic group), an inhibitory expression control group (inhibitor-NC group), and a miR-9-5p inhibitory expression group (inhibitor group). The changes of migration ability were detected by scratch assay. Transwell invasion assay was used to analyze the changes of invasion ability, and the mRNA and protein changes of E-cad and vimentin were detected by quantitative real-time PCR and Western blotting.@*RESULTS@#MiR-9-5p had a targeting binding relationship with E-cad. Compared with the normal cervical tissue H8 cell line, the miR-9-5p was highly expressed in cervical cancer cell lines (C33A, siha, caski and Me180) (all P<0.05). The luciferase activity of E-cad-MUT was increased compared with that of E-cad-WT in miR-9-5p mimic cells (P<0.05). Compared with the blank control group, the protein and mRNA expressions of E-cad were decreased in the miR-9-5p mimic group (both P<0.05), which were increased in the miR-9-5p inhibitor group (both P<0.05). Compared with H8 cell line, the miR-9-5p was highly expressed in the cervical squamous cell lines (all P<0.05). Compared with the mimic-NC group, the distance of wound healing, the number of caski and Me180 cells invaded below the membrane, and the mRNA and protein expressions of vimentin were all increased in the miR-9-5p mimic group (all P<0.05), while the mRNA and protein of E-cad were decreased (both P<0.05). Compared with the inhibitor-NC group, the distance of wound healing, the number of caski and Me180 cells invading the membrane, and the mRNA and protein expressions of vimentin were decreased in the miR-9-5p inhibitor group (all P<0.05), but the mRNA and protein expressions of E-cad were increased (both P<0.05).@*CONCLUSIONS@#The miR-9-5p is highly expressed in cervical squamous cell carcinoma, which can increase the migration and invasion ability, and promote the EMT process of cancer cells.


Assuntos
Humanos , Feminino , Linhagem Celular Tumoral , Vimentina/metabolismo , Neoplasias do Colo do Útero/genética , Transição Epitelial-Mesenquimal/genética , MicroRNAs/metabolismo , Carcinoma de Células Escamosas/genética , Movimento Celular/genética , RNA Mensageiro , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica
11.
Int J Antimicrob Agents ; 60(4): 106650, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35934231

RESUMO

Enterobacter hormaechei, a member of the Enterobacter cloacae complex, has emerged as an important pathogen in healthcare-associated infections. Advancements in phylogenetic analyses and whole-genome sequencing techniques have led to the identification of E. hormaechei in numerous locations worldwide. The emergence of antibiotic-resistant E. hormaechei isolates, including those that produce extended-spectrum ß-lactamases (ESBLs), AmpC ß-lactamases and carbapenemases, has been reported worldwide. In this article, we review the different resistance genes of antibiotic-resistant E. hormaechei.


Assuntos
Infecções por Enterobacteriaceae , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Resistência Microbiana a Medicamentos , Enterobacter , Enterobacter cloacae , Infecções por Enterobacteriaceae/tratamento farmacológico , Humanos , Testes de Sensibilidade Microbiana , Filogenia , beta-Lactamases/genética
12.
Infect Drug Resist ; 15: 167-170, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35082504

RESUMO

We report a COVID-19 case with carbapenem resistant Chryseobacterium indologenes bacteremia. Whole genome sequencing identified the presence of bla IND-2, bla CIA and bla CcrA. To our knowledge, this is the first report of Chryseobacterium indologenes complicating COVID-19 and the detection of bla CcrA in C. indologenes. The presence of bla CcrA in Chryseobacterium was overlooked previously may related to substantial sequence divergence with the original allele in Bacteroides fragilis. Antimicrobial resistance (AMR) is a challenge to global health in the age of COVID-19 pandemic. Further study and surveillance of underlying mechanisms is needed.

13.
Int J Antimicrob Agents ; 59(1): 106475, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34767917

RESUMO

Multidrug-resistant (MDR) bacterial infections in humans are increasing worldwide. The global spread of antimicrobial resistance poses a considerable threat to human health. Phage therapy is a promising approach to combat MDR bacteria. An increasing number of reports have been published on phage therapy and the successful application of antibacterials derived using this method. Additionally, the CRISPR-Cas system has been used to develop antimicrobials with bactericidal effects in vivo. The CRISPR-Cas system can be delivered into target bacteria in various ways, with phage-based vectors being reported as an effective method. In this review, we briefly summarise the results of randomised control trials on bacteriophage therapy. Moreover, we integrated mechanisms of the CRISPR-Cas system antimicrobials in a schematic diagram and consolidated the research on phage-delivered CRISPR-Cas system antimicrobials.


Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Bacteriófagos , Sistemas CRISPR-Cas , Terapia por Fagos/métodos , Farmacorresistência Bacteriana , Humanos
14.
Front Public Health ; 10: 1022055, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36703846

RESUMO

The coronavirus disease (COVID-19) outbreak has turned the world upside down bringing about a massive impact on society due to enforced measures such as the curtailment of personal travel and limitations on economic activities. The global pandemic resulted in numerous people spending their time at home, working, and learning from home hence exposing them to air contaminants of outdoor and indoor origins. COVID-19 is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which spreads by airborne transmission. The viruses found indoors are linked to the building's ventilation system quality. The ventilation flow in an indoor environment controls the movement and advection of any aerosols, pollutants, and Carbon Dioxide (CO2) created by indoor sources/occupants; the quantity of CO2 can be measured by sensors. Indoor CO2 monitoring is a technique used to track a person's COVID-19 risk, but high or low CO2 levels do not necessarily mean that the COVID-19 virus is present in the air. CO2 monitors, in short, can help inform an individual whether they are breathing in clean air. In terms of COVID-19 risk mitigation strategies, intelligent indoor monitoring systems use various sensors that are available in the marketplace. This work presents a review of scientific articles that influence intelligent monitoring development and indoor environmental quality management system. The paper underlines that the non-dispersive infrared (NDIR) sensor and ESP8266 microcontroller support the development of low-cost indoor air monitoring at learning facilities.


Assuntos
Poluição do Ar em Ambientes Fechados , COVID-19 , Humanos , SARS-CoV-2 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Dióxido de Carbono , Poluição do Ar em Ambientes Fechados/prevenção & controle , Poluição do Ar em Ambientes Fechados/análise , Aerossóis e Gotículas Respiratórios
15.
Mol Brain ; 14(1): 152, 2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34607601

RESUMO

The glutamatergic signaling pathway is involved in molecular learning and human cognitive ability. Specific single variants (SNVs, formerly single-nucleotide polymorphisms) in the genes encoding N-methyl-D-aspartate receptor subunits have been associated with neuropsychiatric disorders by altering glutamate transmission. However, these variants associated with cognition and mental activity have rarely been explored in healthy adolescents. In this study, we screened for SNVs in the glutamatergic signaling pathway to identify genetic variants associated with cognitive ability. We found that SNVs in the subunits of ionotropic glutamate receptors, including GRIA1, GRIN1, GRIN2B, GRIN2C, GRIN3A, GRIN3B, and calcium/calmodulin-dependent protein kinase IIα (CaMK2A) are associated with cognitive function. Plasma CaMK2A level was correlated positively with the cognitive ability of Taiwanese senior high school students. We demonstrated that elevating CaMK2A increased its autophosphorylation at T286 and increased the expression of its downstream targets, including GluA1 and phosphor- GluA1 in vivo. Additionally, methyl-CpG binding protein 2 (MeCP2), a downstream target of CaMK2A, was found to activate the expression of CaMK2A, suggesting that MeCP2 and CaMK2A can form a positive feedback loop. In summary, two members of the glutamatergic signaling pathway, CaMK2A and MeCP2, are implicated in the cognitive ability of adolescents; thus, altering the expression of CaMK2A may affect cognitive ability in youth.


Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/fisiologia , Cognição/fisiologia , Proteína 2 de Ligação a Metil-CpG/fisiologia , Psicologia do Adolescente , Receptores Ionotrópicos de Glutamato/genética , Transdução de Sinais/fisiologia , Adolescente , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/sangue , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Linhagem Celular Tumoral , Ativação Enzimática , Retroalimentação Fisiológica/fisiologia , Feminino , Ácido Glutâmico/fisiologia , Células HEK293 , Humanos , Masculino , Neuroblastoma , Fosforilação , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Processamento de Proteína Pós-Traducional , Receptores Ionotrópicos de Glutamato/fisiologia , Valores de Referência , Taiwan
16.
Ergonomics ; 64(9): 1174-1182, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33938408

RESUMO

This study examined the variation in individuals' static maximum forward pushing and backward pulling (FPBP) strength for handleless cartons under different task conditions. Thirty young Taiwanese men were recruited as participants and were requested to perform maximum FPBP exertion tests under four exertion heights (50, 80, 110, and 140 cm), two types of hand contact (bare hands and gloves), and two carton widths (40 and 60 cm). The results of this study indicated that the pushing strength for handleless cartons was almost twice the pulling strength for all exertion heights. This finding is different from those of previous relevant studies. The pulling force generated when gloves were worn was 38% higher than that generated under barehanded pulling. Moreover, the pulling force generated with a 40-cm-wide carton was 13% higher than that generated with a 60-cm-wide carton. Pushing strength was affected by only the exertion height. Practitioner Summary: We examined the effects of exertion height, carton width, and type of contact on the maximum FPBP strengths. Pulling strength should be considered first for the related task design because it is lower than pushing strength. However, pulling strength can be maximised by wearing gloves to pull a 60-cm-wide carton. Abbreviations: FPBP: forward pushing and backward pulling; ANOVA: analysis of varianceHIGHLIGHTSMaximum forward pushing and backward pulling (FPBP) forces vary for cartons.FPBP forces for force direction, contact type, carton width, and exertion height were examined.FPBP forces generated for handleless cartons differ from those generated for cartons with handles.Pulling strength can be maximised by wearing gloves and using a 60-cm-wide carton.Gloves are useful tools for pulling handleless cartons.


Assuntos
Mãos , Fenômenos Biomecânicos , Humanos , Masculino
18.
ACS Appl Mater Interfaces ; 13(2): 2483-2495, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33404219

RESUMO

Influenza, pneumonia, and pathogenic infection of the respiratory system are boosted in cold environments. Low temperatures also result in vasoconstriction, restraint of blood flow, and decreased oxygen to the heart, and the risk of a heart attack would increase accordingly. The present face mask fabric fails to preserve its air-filtering function as its electrostatic function vanishes once exposed to water. Therefore, its filtering efficacy would be decreased meaningfully, making it nearly impracticable to reuse the disposable face masks. The urgent requirement for photothermal fabrics is also rising. Nanobased polyethyleneimine-polypyrrole nanopigments (NPP NPs) have been developed and have strong near-infrared spectrum absorption and exceptional photothermal convertible performance. Herein, the mask fabric used PE-fiber-constructed membrane (PEFM) was coated by the binding affinity of the cationic polyethyleneimine component of NPP NPs forming NPP NPs-PEFM. To the best of our knowledge, no study has investigated NPP NP-coated mask fabric to perform infrared red (solar or body) photothermal conversion efficacy to provide biocompatible warming, remotely photothermally captured antipathogen, and antivasoconstriction in vivo. This pioneering study showed that the developed NPP NPs-PEFM could be washable, reusable, breathable, biocompatible, and photothermal conversable for active eradication of pathogenic bacteria. Further, it possesses warming preservation and antivasoconstriction.


Assuntos
Materiais Revestidos Biocompatíveis/química , Nanoestruturas/química , Polietileno/química , Polietilenoimina/química , Polímeros/química , Pirróis/química , Têxteis/análise , Animais , Antibacterianos/química , Raios Infravermelhos , Máscaras/microbiologia , Nanoestruturas/ultraestrutura , Processos Fotoquímicos , Coelhos , Ratos , Temperatura , Têxteis/microbiologia
19.
J Microbiol Immunol Infect ; 53(3): 481-484, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32111449
20.
Immunohorizons ; 3(12): 559-572, 2019 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791977

RESUMO

Use of recombinant viral vectors encoding nonnative Ags is an attractive mechanism for the generation of protective Ab, CD4+ T cell (TCD4+), and CD8+ T cell (TCD8+) responses in vivo following immunization. However, the life cycle and tropism of the viral vector, and its interactions with various components of the immune system, must be fully understood to maximize the efficacy of any vaccination strategies. Ab and TCD4+ responses typically target native Ags driven by late promoters in vaccinia virus (VACV)-based vectors. However, it has been demonstrated that model Ags driven by late promoters in recombinant VACV vectors do not stimulate TCD8+ responses, whereas identical Ags driven by early promoters stimulate strong responses. Conversely, TCD8+ can be generated against some natural late VACV Ags. We explored this dichotomy by investigating the Ag presentation pathways responsible for presentation of natural late VACV Ags in mice. We found that all of the late VACV Ags we examined could be cross-primed (i.e., presented by uninfected professional APC), as well as directly presented by infected dendritic cell populations. However, one Ag was only presented by professional APC populations and was not the target of a protective TCD8+ response. Therefore, there is no generalized blockade in Ag presentation of late VACV Ags, and expression of nonnative Ags driven by a late promoter allows production of large quantities of Ag that may allow simultaneous targeting of both TCD4+ and Ab responses, as well as TCD8+ responses, in the future.


Assuntos
Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Vaccinia virus/imunologia , Vacínia/metabolismo , Proteínas Virais/metabolismo , Animais , Células Apresentadoras de Antígenos/imunologia , Antígenos Virais/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Células Dendríticas/imunologia , Epitopos de Linfócito T/imunologia , Vetores Genéticos , Células HeLa , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Regiões Promotoras Genéticas/imunologia , Vacínia/virologia
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