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1.
Nature ; 511(7511): 601-5, 2014 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-25043006

RESUMO

Inflammation in HIV infection is predictive of non-AIDS morbidity and death, higher set point plasma virus load and virus acquisition; thus, therapeutic agents are in development to reduce its causes and consequences. However, inflammation may simultaneously confer both detrimental and beneficial effects. This dichotomy is particularly applicable to type I interferons (IFN-I) which, while contributing to innate control of infection, also provide target cells for the virus during acute infection, impair CD4 T-cell recovery, and are associated with disease progression. Here we manipulated IFN-I signalling in rhesus macaques (Macaca mulatta) during simian immunodeficiency virus (SIV) transmission and acute infection with two complementary in vivo interventions. We show that blockade of the IFN-I receptor caused reduced antiviral gene expression, increased SIV reservoir size and accelerated CD4 T-cell depletion with progression to AIDS despite decreased T-cell activation. In contrast, IFN-α2a administration initially upregulated expression of antiviral genes and prevented systemic infection. However, continued IFN-α2a treatment induced IFN-I desensitization and decreased antiviral gene expression, enabling infection with increased SIV reservoir size and accelerated CD4 T-cell loss. Thus, the timing of IFN-induced innate responses in acute SIV infection profoundly affects overall disease course and outweighs the detrimental consequences of increased immune activation. Yet, the clinical consequences of manipulation of IFN signalling are difficult to predict in vivo and therapeutic interventions in human studies should be approached with caution.


Assuntos
Progressão da Doença , Interferon-alfa/uso terapêutico , Macaca mulatta/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios , Vírus da Imunodeficiência Símia/imunologia , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Regulação da Expressão Gênica/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Interferon-alfa/farmacologia , Estimativa de Kaplan-Meier , Transdução de Sinais/efeitos dos fármacos , Síndrome de Imunodeficiência Adquirida dos Símios/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle
2.
PLoS One ; 19(7): e0306602, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38995889

RESUMO

The insectivorous Northern Pitcher Plant, Sarracenia purpurea, recruits a dynamic biotic community in the rainwater collected by its pitcher-shaped leaves. Insect capture and degradation within the pitcher fluid (phytotelma) has been well documented as a mechanism for supplementing the plant's nitrogen, phosphorous, and micronutrient requirements. Metagenomic studies have shown a diverse microbiome in this phytotelm environment, including taxa that contribute metabolically to prey digestion. In this investigation, we used high-throughput 16S rDNA sequencing and bioinformatics to analyze the S. purpurea phytotelm bacteriome as it changes through the growing season (May-September) in plants from the north-central region of the species' native range. Additionally, we used molecular techniques to detect and quantify bacterial nitrogenase genes (nifH) in all phytotelm samples to explore the hypothesis that diazotrophy is an additional mechanism of supplying biologically available nitrogen to S. purpurea. The results of this study indicate that while prokaryote diversity remains relatively stable in plants at different locations within our region, diversity changes significantly as the growing season progresses. Furthermore, nifH genes were detected at biologically significant concentrations in one hundred percent of samples, suggesting that nitrogen fixation may be an important contributor to the S. purpurea nutrient budget.


Assuntos
Sarraceniaceae , Estações do Ano , Sarraceniaceae/microbiologia , Microbiota/genética , RNA Ribossômico 16S/genética , Nitrogênio/metabolismo , Bactérias/genética , Bactérias/classificação , Bactérias/isolamento & purificação , Fixação de Nitrogênio , Oxirredutases/genética , Oxirredutases/metabolismo
3.
Ned Tijdschr Geneeskd ; 1642020 09 03.
Artigo em Holandês | MEDLINE | ID: mdl-33030332

RESUMO

The development of an HIV vaccine has been a major challenge for several decades already. In order to cope with the large diversity and mutation rate of the virus, a vaccine needs to offer extraordinarily broad protection. In recent years, a large number of clinical studies all over the world have been investigating promising new vaccine strategies. Findings of these studies will provide important guidance for further optimisation of vaccine candidates, excipients and vaccination schedules in the near future. Vaccines currently under investigation are stimulating either the development of antibodies against HIV or antiviral T-cell immunity. In order to provide broad and long-lasting protection, an effective vaccine should induce both humoral and cellular responses, which could be achieved with sequential immunisations as well as a combination of several different vaccine strategies.


Assuntos
Vacinas contra a AIDS/imunologia , Vacinas contra a AIDS/uso terapêutico , Síndrome da Imunodeficiência Adquirida/prevenção & controle , Anticorpos Anti-HIV/imunologia , Infecções por HIV/prevenção & controle , Síndrome da Imunodeficiência Adquirida/imunologia , Ensaios Clínicos como Assunto , Infecções por HIV/imunologia , Humanos , Imunidade Celular , Imunidade Humoral , Mutação
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