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Human adenovirus-36 (HAdV-36) infection has been linked to obesity, low lipid levels, and improvements in blood glucose levels and insulin sensitivity in animal models and humans, although epidemiological studies remain controversial. Therefore, this study investigated the relationship between HAdV-36 seropositivity and glycemic control in youths. This observational study examined 460 youths (246 with normal weight and 214 obese subjects). All participants underwent assessments for anthropometry, blood pressure, circulating fasting levels of glucose, lipids, insulin, and anti-HAdV-36 antibodies; additionally, the homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. In all, 57.17% of the subjects were HAdV-36 seropositive. Moreover, HAdV-36 seroprevalence was higher in obese subjects compared to their normal weight counterparts (59% vs. 55%). BMI (33.1 vs. 32.3 kg/m2, p = 0.03), and waist circumference (107 vs. 104 cm, p = 0.02), insulin levels (21 vs. 16.3 µU/mL, p = 0.003), and HOMA-IR (4.6 vs. 3.9, p = 0.02) were higher in HAdV-36-positive subjects with obesity compared to seronegative subjects. In the obese group, HAdV-36 seropositivity was associated with a reducing effect in blood glucose levels in a model adjusted for total cholesterol, triglyceride levels, age and sex (ß = -10.44, p = 0.014). Furthermore, a statistically significant positive relationship was observed between HAdV-36 seropositivity and insulin levels in the obesity group. These findings suggest that natural HAdV-36 infection improves glycemic control but does not ameliorate hyperinsulinemia in obese subjects.
Assuntos
Infecções por Adenovirus Humanos , Adenovírus Humanos , Glicemia , Resistência à Insulina , Insulina , Obesidade , Humanos , Masculino , Feminino , Glicemia/análise , Insulina/sangue , Adolescente , Obesidade/sangue , Infecções por Adenovirus Humanos/sangue , Infecções por Adenovirus Humanos/epidemiologia , Infecções por Adenovirus Humanos/virologia , Criança , Estudos Soroepidemiológicos , Adulto Jovem , Índice de Massa Corporal , Anticorpos Antivirais/sangueRESUMO
Dorper rams (n = 24) were evaluated during the sexual resting season to determine their social rank (SR), either high (HSR) or low (LSR), under intensive management conditions in northern Mexico (25° N). Aggressive behaviors were quantified during male-to-male interactions, and appetitive and consummatory sexual behaviors during male-to-female interactions. Morphometric, live weight (LW), and body condition score (BCS) were recorded. During the early reproductive season, male-to-female behaviors were newly itemized simultaneously by seminal quality and quantity sampling. Finally, the dependent variables of the hemogram components were also quantified. Neither LW (61.25 ± 2.4 kg) nor morphometric variables differed between SR groups. However, BCS (2.25 vs. 2.66 u), sexual behaviors (i.e., approaches: 59.6 vs. 21.73 n, mating with ejaculation: 77.7 vs. 42.86 %, latency to ejaculation: 16.6 vs. 143.07 s), ejaculate volume (0.57 vs. 0.23 mL), and hemogram components favored the HSR rams (p < 0.05). Moreover, in their first male-to-female interaction, >50% of the LSR rams failed to display any sexual activity. HSR rams displayed a greater number of threatening behaviors, managing to displace LSR rams when exposed to estrus ewes during the male sexual resting season; more sexual behaviors; and an increased seminal volume in a non-live weight-dependent fashion.
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Human adenovirus 36 (HAdV-D36) can cause obesity in animal models, induces an adipogenic effect and increased adipocyte differentiation in cell culture. HAdV-D36 infection alters gene expression and the metabolism of the infected cells resulting in increased glucose internalization and triglyceride accumulation. Although HAdV-D36 prevalence correlates with obesity in humans, whether human preadipocytes may be targeted in vivo has not been determined and metabolic reprogramming of preadipocytes has not been explored in the context of the viral replication cycle. HAdV-D36 infection of the mouse fibroblasts, 3T3-L1 cells, which can differentiate into adipocytes, promotes proliferation and differentiation, but replication of the virus in these cells is abortive as indicated by short-lived transient expression of viral mRNA and a progressive loss of viral DNA. Therefore, we have evaluated whether a productive viral replication cycle can be established in the 3T3-L1 preadipocyte model under conditions that drive the cell differentiation process. For this purpose, viral mRNA levels and viral DNA replication were measured by RT-qPCR and qPCR, respectively, and viral progeny production was determined by plaque assay. The lipogenic effect of infection was evaluated with Oil Red O (ORO) staining, and expression of genes that control lipid and glucose metabolism was measured by RT-qPCR. In the context of a viral productive cycle, HAdV-D36 modulated the expression of the adipogenic genes, C/EBPα, C/EBPß and PPARγ, as well as intracellular lipid accumulation, and the infection was accompanied by altered expression of glucolytic genes. The results show that only adipocyte-committed 3T3-L1 cells are permissive for the expression of early and late viral mRNAs, as well as viral DNA replication and progeny production, supporting productive HAdV-D36 viral replication, indicating that a greater effect on adipogenesis occurs in adipocytes that support productive viral replication.
Assuntos
Infecções por Adenovirus Humanos , Adenovírus Humanos , Células 3T3-L1 , Adenovírus Humanos/genética , Adipócitos , Animais , Diferenciação Celular , Replicação do DNA , DNA Viral , Glucose/metabolismo , Humanos , Metabolismo dos Lipídeos , Lipídeos/farmacologia , Camundongos , Obesidade , PPAR gama/genética , PPAR gama/metabolismo , PPAR gama/farmacologia , RNA Mensageiro/metabolismo , Triglicerídeos/metabolismo , Replicação ViralRESUMO
A common viral replication strategy is characterized by the assembly of intracellular compartments that concentrate factors needed for viral replication and simultaneously conceal the viral genome from host-defense mechanisms. Recently, various membrane-less virus-induced compartments and cellular organelles have been shown to represent biomolecular condensates (BMCs) that assemble through liquid-liquid phase separation (LLPS). In the present work, we analyze biophysical properties of intranuclear replication compartments (RCs) induced during human adenovirus (HAdV) infection. The viral ssDNA-binding protein (DBP) is a major component of RCs that contains intrinsically disordered and low complexity proline-rich regions, features shared with proteins that drive phase transitions. Using fluorescence recovery after photobleaching (FRAP) and time-lapse studies in living HAdV-infected cells, we show that DBP-positive RCs display properties of liquid BMCs, which can fuse and divide, and eventually form an intranuclear mesh with less fluid-like features. Moreover, the transient expression of DBP recapitulates the assembly and liquid-like properties of RCs in HAdV-infected cells. These results are of relevance as they indicate that DBP may be a scaffold protein for the assembly of HAdV-RCs and should contribute to future studies on the role of BMCs in virus-host cell interactions.
Assuntos
Adenoviridae/metabolismo , Condensados Biomoleculares , Proteínas de Ligação a DNA/metabolismo , Compartimentos de Replicação Viral/fisiologia , Replicação Viral/fisiologia , Adenoviridae/genética , Infecções por Adenoviridae , Adenovírus Humanos/metabolismo , Linhagem Celular , Proteínas de Ligação a DNA/química , Interações entre Hospedeiro e Microrganismos , Humanos , Organelas/virologia , Domínios Proteicos , Proteínas Virais/química , Proteínas Virais/genética , Proteínas Virais/metabolismoRESUMO
Coronaviruses (CoV) are enveloped, plus-strand RNA viruses that have the largest known RNA genomes and infect birds and mammals, causing various diseases. Human coronaviruses (HCoVs) were first identified in the mid-1960s and have been known to cause enteric or respiratory infections. In the last two decades, three HCoVs have emerged, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which initiated the ongoing pandemic. SARS-CoV-2 causes a respiratory illness that presents as a mild upper respiratory disease but may result in acute respiratory distress syndrome, multi-organ failure and can be fatal, especially when underlying comorbidities are present. Children account for a low percentage of coronavirus disease 2019 (COVID-19) cases, with seemingly less severe disease. Most pediatric patients present mild or moderate symptoms or are asymptomatic. However, some cases may be severe. Therefore, SARS-CoV-2 infection and COVID-19 in pediatric patients must be studied in detail. This review describes general features of the molecular biology of CoVs and virus-host interactions that may be implicated in the pathogenesis of SARS-CoV-2.
Los coronavirus son virus envueltos de ARN de polaridad positiva, con los genomas más grandes que se conocen. Infectan aves y mamíferos, y causan una amplia variedad de enfermedades. Los coronavirus humanos se identificaron a mediados de la década de 1960 y se sabe que causan infecciones entéricas y respiratorias. En las últimas dos décadas han emergido tres coronavirus humanos pandémicos, incluido el coronavirus 2 del síndrome agudo respiratorio grave (SARS-CoV-2) que ha causado la pandemia actual. El SARS-CoV-2 produce enfermedad respiratoria que se presenta con padecimientos moderados de las vías respiratorias altas, pero puede resultar en síndrome respiratorio agudo, falla multiorgánica y muerte, en especial en casos con morbilidad subyacente. Los casos de COVID-19 en niños representan un porcentaje bajo y con síntomas menos graves de la enfermedad. La mayoría de los pacientes pediátricos son asintomáticos o presentan enfermedad leve o moderada; sin embargo, también en niños la enfermedad puede ser grave, por lo que la infección con SARS-CoV-2 y la COVID-19 en pacientes pediátricos deben estudiarse con detalle. En esta revisión se describen las características generales de la biología molecular de los coronavirus y de las interacciones virus-hospedero que se conocen para los coronavirus humanos identificados previamente, y que podrían estar implicados en la patogénesis del SARS-CoV-2.
Assuntos
COVID-19/virologia , Infecções por Coronavirus/virologia , Coronavirus/genética , Animais , COVID-19/epidemiologia , Criança , Coronavirus/classificação , Coronavirus/isolamento & purificação , Infecções por Coronavirus/classificação , Infecções por Coronavirus/epidemiologia , Humanos , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de DoençaRESUMO
Abstract Coronaviruses (CoV) are enveloped, plus-strand RNA viruses that have the largest known RNA genomes and infect birds and mammals, causing various diseases. Human coronaviruses (HCoVs) were first identified in the mid-1960s and have been known to cause enteric or respiratory infections. In the last two decades, three HCoVs have emerged, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which initiated the ongoing pandemic. SARS-CoV-2 causes a respiratory illness that presents as a mild upper respiratory disease but may result in acute respiratory distress syndrome, multi-organ failure and can be fatal, especially when underlying comorbidities are present. Children account for a low percentage of coronavirus disease 2019 (COVID-19) cases, with seemingly less severe disease. Most pediatric patients present mild or moderate symptoms or are asymptomatic. However, some cases may be severe. Therefore, SARS-CoV-2 infection and COVID-19 in pediatric patients must be studied in detail. This review describes general features of the molecular biology of CoVs and virus-host interactions that may be implicated in the pathogenesis of SARS-CoV-2.
Resumen Los coronavirus son virus envueltos de ARN de polaridad positiva, con los genomas más grandes que se conocen. Infectan aves y mamíferos, y causan una amplia variedad de enfermedades. Los coronavirus humanos se identificaron a mediados de la década de 1960 y se sabe que causan infecciones entéricas y respiratorias. En las últimas dos décadas han emergido tres coronavirus humanos pandémicos, incluido el coronavirus 2 del síndrome agudo respiratorio grave (SARS-CoV-2) que ha causado la pandemia actual. El SARS-CoV-2 produce enfermedad respiratoria que se presenta con padecimientos moderados de las vías respiratorias altas, pero puede resultar en síndrome respiratorio agudo, falla multiorgánica y muerte, en especial en casos con morbilidad subyacente. Los casos de COVID-19 en niños representan un porcentaje bajo y con síntomas menos graves de la enfermedad. La mayoría de los pacientes pediátricos son asintomáticos o presentan enfermedad leve o moderada; sin embargo, también en niños la enfermedad puede ser grave, por lo que la infección con SARS-CoV-2 y la COVID-19 en pacientes pediátricos deben estudiarse con detalle. En esta revisión se describen las características generales de la biología molecular de los coronavirus y de las interacciones virus-hospedero que se conocen para los coronavirus humanos identificados previamente, y que podrían estar implicados en la patogénesis del SARS-CoV-2.
Assuntos
Animais , Criança , Humanos , Infecções por Coronavirus/virologia , Coronavirus/genética , COVID-19/virologia , Índice de Gravidade de Doença , Infecções por Coronavirus/classificação , Infecções por Coronavirus/epidemiologia , Coronavirus/isolamento & purificação , Coronavirus/classificação , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/genética , COVID-19/epidemiologiaRESUMO
The adenovirus E1B 55K (E1B) protein plays major roles in productive adenoviral infection and cellular transformation. Interest in E1B increased because of the potential of adenoviruses as therapeutic vectors, and the E1B gene is commonly deleted from adenovirus vectors for anticancer therapy. E1B activities are spatiotemporally regulated through SUMOylation and phosphorylation, and through interactions with multiple partners that occur presumably at different intracellular sites and times postinfection. E1B is implicated in the formation of viral replication compartments and regulates viral genome replication and transcription, transcriptional repression, degradation of cellular proteins, and several intranuclear steps of viral late mRNA biogenesis. Here, we review advances in our understanding of E1B during productive adenovirus replication and discuss fundamental aspects that remain unresolved.
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Adenoviridae/fisiologia , Proteínas E1B de Adenovirus/química , Proteínas E1B de Adenovirus/metabolismo , Adenoviridae/metabolismo , Regulação Viral da Expressão Gênica , Modelos Moleculares , Fosforilação , Conformação Proteica , Sumoilação , Replicação ViralRESUMO
Viruses are the most abundant biological entities in the biosphere, and have the ability to infect Bacteria, Archaea, and Eukaryotes. The virome is estimated to be at least ten times more abundant than the microbiome with 107 viruses per milliliter and 109 viral particles per gram in marine waters and sediments or soils, respectively. Viruses represent a largely unexplored genetic diversity, having an important role in the genomic plasticity of their hosts. Moreover, they also play a significant role in the dynamics of microbial populations. In recent years, metagenomic approaches have gained increasing popularity in the study of environmental viromes, offering the possibility of extending our knowledge related to both virus diversity and their functional characterization. Extreme environments represent an interesting source of both microbiota and their virome due to their particular physicochemical conditions, such as very high or very low temperatures and >1 atm hydrostatic pressures, among others. Despite the fact that some progress has been made in our understanding of the ecology of the microbiota in these habitats, few metagenomic studies have described the viromes present in extreme ecosystems. Thus, limited advances have been made in our understanding of the virus community structure in extremophilic ecosystems, as well as in their biotechnological potential. In this review, we critically analyze recent progress in metagenomic based approaches to explore the viromes in extreme environments and we discuss the potential for new discoveries, as well as methodological challenges and perspectives.
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Adenoviruses induce an extensive reorganization of the host cell nucleus during replication. Such a process results in the assembly of viral and cellular macromolecules into nuclear structures called adenovirus replication compartments (AdRCs), which function as platforms for viral DNA replication and gene expression. AdRCs co-opt host proteins and cellular pathways that restrict viral replication, suggesting that the mechanisms that control AdRC formation and function are essential for viral replication and lay at the basis of virus-host interactions. Here, we review the hallmarks of AdRCs and recent progress in our understanding of the formation, composition, and function of AdRCs. Furthermore, we discuss how AdRCs facilitate the interplay between viral and cellular machineries and hijack cellular functions to promote viral genome replication and expression.
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Infecções por Adenoviridae/virologia , Adenoviridae/fisiologia , DNA Viral/genética , Adenoviridae/genética , Infecções por Adenoviridae/metabolismo , Animais , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Regulação Viral da Expressão Gênica , Interações Hospedeiro-Patógeno , Humanos , Proteínas Virais/genética , Replicação ViralRESUMO
The use of latency reversing agents (LRAs) is currently a promising approach to eliminate latent reservoirs of HIV-1. However, this strategy has not been successful in vivo. It has been proposed that cellular post-transcriptional mechanisms are implicated in the underperformance of LRAs, but it is not clear whether proviral regulatory elements like viral non-coding RNAs (vncRNAs) are also implicated. In order to visualize the complexity of the HIV-1 gene expression, we used experimental data to construct a gene regulatory network (GRN) of latent proviruses in resting CD4+ T cells. We then analyzed the dynamics of this GRN using Boolean and continuous mathematical models. Our simulations predict that vncRNAs are able to counteract the activity of LRAs, which may explain the failure of these compounds to reactivate latent reservoirs of HIV-1. Moreover, our results also predict that using inhibitors of histone methyltransferases, such as chaetocin, together with releasers of the positive transcription elongation factor (P-TEFb), like JQ1, may increase proviral reactivation despite self-repressive effects of vncRNAs.
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Se muestrearon 50 palomas Columba livia de 5 zonas del área metropolitana de la ciudad de México y 10 de Ixtlahuaca, Estado de México, con la finalidad de medir las concentraciones de plomo, cadmio y cromo, las características histológicas de encéfalo, pulmón, hígado y riñon y las alteraciones ultraestructurales utilizando nicroscopia electrónica de barrido en el caso de pulmón. Las concentraciones más altas de plomo se observaron en el riñón, con 11.03 ppm, en la Merced; de cadmio, en riñón con 6,86 ppm y en el Pedregal de San Angel y con 6.07 ppm en Tlalnepantla. Las muestras del municipio de Ixtlahuacan tuvieron siempre los valores más bajos y las concentraciones más altas fueron: plomo, 2.19 ppm, en hígado; cadmio, 0.91 ppm, en riñón, y cromo, 1.54 ppm, en encéfalo. Las concentraciones promedio de plomo en las palomas de la ciudad de México fueron en riñón 7.6, en encéfalo 5.15, en hígado 3.92 y en pulmón 3.64 ppm. Las concentraciones promedio del cadmio fueron: en rinón, 5.32; hígado, 1.04; encéfalo 0.86 y pulmón 0.58 ppm. Los valores promedio de cromo fueron: riñón, 4.34; encéfalo; 3.79; pulmón; 2.65 y en hígado 1.77 ppm. Lo observado en el pulmón a nivel ultraestructural fueron partículas en las muestras de las zonas de Tlalnepantla, San Felipe y La Merced, pero no se observaron cuerpo ferruginosos en el estudio histológico. Los principales hallazgos histológicos encontrados fueron: Infiltración linfocitaria multifocal en pulmón, Hígado y riñón, así como hemosiderina en pulmón e hígado y antracosis en pulmón, además de metaplasia ósea en el parénquima pulmonar en un solo caso