RESUMO
The notion that viruses played a crucial role in the evolution of life is not a new concept. However, more recent insights suggest that this perception might be even more expansive, highlighting the ongoing impact of viruses on host evolution. Endogenous retroviruses (ERVs) are considered genomic remnants of ancient viral infections acquired throughout vertebrate evolution. Their exogenous counterparts once infected the host's germline cells, eventually leading to the permanent endogenization of their respective proviruses. The success of ERV colonization is evident so that it constitutes 8% of the human genome. Emerging genomic studies indicate that endogenous retroviruses are not merely remnants of past infections but rather play a corollary role, despite not fully understood, in host genetic regulation. This review presents some evidence supporting the crucial role of endogenous retroviruses in regulating host genetics. We explore the involvement of human ERVs (HERVs) in key physiological processes, from their precise and orchestrated activities during cellular differentiation and pluripotency to their contributions to aging and cellular senescence. Additionally, we discuss the costs associated with hosting a substantial amount of preserved viral genetic material.
Assuntos
Retrovirus Endógenos , Retrovirus Endógenos/genética , Retrovirus Endógenos/fisiologia , Humanos , Animais , Diferenciação Celular , Interações Hospedeiro-Patógeno/genética , Interações entre Hospedeiro e Microrganismos/genética , Infecções por Retroviridae/virologia , Senescência Celular/genética , Provírus/genética , Provírus/fisiologia , Evolução MolecularRESUMO
Legume plants establish a nitrogen-fixing symbiosis with soil bacteria known as rhizobia. Compatibility between legumes and rhizobia is determined at species-specific level, but variations in the outcome of the symbiotic process are also influenced by the capacity of the plant to discriminate and select specific strains that are better partners. We compared the transcriptional response of two genetically diverse accessions of Phaseolus vulgaris from Mesoamerica and South Andes to Rhizobium etli strains that exhibit variable degrees of symbiotic affinities. Our results indicate that the plant genotype is the major determinant of the transcriptional reprogramming occurring in roots at early stages of the symbiotic interaction. Differentially expressed genes (DEGs) regulated in the Mesoamerican and the Andean accessions in response to specific strains are different, but they belong to the same functional categories. The common and strain-specific transcriptional responses to rhizobia involve distinct transcription factors and cis-elements present in the promoters of DEGs in each accession, showing that diversification and domestication of common bean at different geographic regions influenced the evolution of symbiosis differently in each genetic pool. Quantitative PCR analysis validated our transcriptional datasets, which constitute a valuable source of coding and non-coding candidate genes to further unravel the molecular determinants governing the mechanisms by which plants select bacterial strains that produce a better symbiotic outcome.
Assuntos
Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica de Plantas/genética , Phaseolus/genética , Phaseolus/fisiologia , RNA Longo não Codificante/genética , RNA Mensageiro/genética , RNA de Plantas/genética , Simbiose/genética , Simbiose/fisiologia , Transcriptoma/genética , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/fisiologia , Rhizobiaceae/fisiologia , Microbiologia do Solo , Especificidade da EspécieRESUMO
Studies on the feeding behavior of hematophagous insects, particularly those of medical importance, are relevant for tracking possible pathogen transmission routes and identifying biases in the choice of vertebrates. We evaluated host selection of blood-feeding mosquitoes in a disturbed forest in the Magdalena Medio valley in Colombia from March 2017 to April 2018, after the introduction of Zika virus to the Americas from the 2015-2016 outbreak. We estimated vertebrate diversity and collected blood-engorged female mosquitoes. Genomic DNA/RNA was extracted from the mosquito's abdomen for vertebrate host identification and pathogen detection. We performed conventional PCR and sequencing, using universal primers targeting vertebrate regions of the eukaryotic mitochondrial genome to determine bloodmeal host. Additionally, we tested for the presence of flaviviruses in all mosquito samples with RT-PCR. Based on the identity and quantity of detected bloodmeals, we performed mosquito-vertebrate interaction network analysis and estimated topology metrics. In total, we collected 292 engorged female mosquitoes representing 20 different species. Bloodmeal analyses identified 26 vertebrate species, the majority of which were mammals (N = 16; 61.5%). No flaviviruses of medical importance were detected from the samples. Although feeding patterns varied, network analyses showed a high degree of specialization by mosquitoes and revealed ecological and phylogenetic relationships among the host community. We conclude that host selection or preference by mosquitoes is species specific.
Assuntos
Culicidae/genética , Flavivirus/genética , Interações entre Hospedeiro e Microrganismos/fisiologia , Animais , Anopheles/virologia , Colômbia , Culicidae/metabolismo , Culicidae/virologia , Comportamento Alimentar/fisiologia , Feminino , Flavivirus/patogenicidade , Interações entre Hospedeiro e Microrganismos/genética , Mamíferos , Mosquitos Vetores/virologia , Filogenia , Floresta Úmida , Especificidade da Espécie , VertebradosRESUMO
The plant growth-promoting bacterium Azospirillum brasilense contains several genes encoding proteins involved in the biosynthesis and degradation of the second messenger cyclic-di-GMP, which may control key bacterial functions, such as biofilm formation and motility. Here, we analysed the function and expression of the cdgD gene, encoding a multidomain protein that includes GGDEF-EAL domains and CHASE and PAS domains. An insertional cdgD gene mutant was constructed, and analysis of biofilm and extracellular polymeric substance production, as well as the motility phenotype indicated that cdgD encoded a functional diguanylate protein. These results were correlated with a reduced overall cellular concentration of cyclic-di-GMP in the mutant over 48 h compared with that observed in the wild-type strain, which was recovered in the complemented strain. In addition, cdgD gene expression was measured in cells growing under planktonic or biofilm conditions, and differential expression was observed when KNO3 or NH4Cl was added to the minimal medium as a nitrogen source. The transcriptional fusion of the cdgD promoter with the gene encoding the autofluorescent mCherry protein indicated that the cdgD gene was expressed both under abiotic conditions and in association with wheat roots. Reduced colonization of wheat roots was observed for the mutant compared with the wild-type strain grown in the same soil conditions. The Azospirillum-plant association begins with the motility of the bacterium towards the plant rhizosphere followed by the adsorption and adherence of these bacteria to plant roots. Therefore, it is important to study the genes that contribute to this initial interaction of the bacterium with its host plant.
Assuntos
Azospirillum brasilense/genética , GMP Cíclico/genética , GMP Cíclico/metabolismo , Regulação Bacteriana da Expressão Gênica/genética , Expressão Gênica , Interações entre Hospedeiro e Microrganismos/genética , Domínios Proteicos/genética , Azospirillum brasilense/fisiologia , Aderência Bacteriana , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Mutação , Raízes de Plantas/microbiologia , Sistemas do Segundo Mensageiro , Triticum/microbiologiaRESUMO
The Epstein-Barr Virus (EBV) is a gamma-herpesvirus involved with a variety of human cancers, notably the endemic Burkitt lymphoma and nasopharyngeal carcinoma. In 2004, EBV was described as one the first known human oncoviruses to encode viral microRNAs (miRNAs), and these molecules were found to interact with viral and host targets. EBV miRNAs modulate biological processes that are critical for carcinogenesis, contributing to cell transformation and tumor progression of EBV-associated cancers. Herein we review and discuss EBV miRNAs as modulators of viral biology and carcinogenesis, as well as their usefulness as putative markers to monitor the onset, progression, and recurrence of cancers associated with the EBV infection.
Assuntos
Transformação Celular Neoplásica/genética , Infecções por Vírus Epstein-Barr/patologia , Herpesvirus Humano 4/patogenicidade , MicroRNAs/metabolismo , Neoplasias/virologia , RNA Viral/metabolismo , Animais , Linhagem Celular Tumoral , Transformação Celular Neoplásica/imunologia , Progressão da Doença , Infecções por Vírus Epstein-Barr/virologia , Regulação Neoplásica da Expressão Gênica/imunologia , Herpesvirus Humano 4/genética , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Camundongos , MicroRNAs/análise , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/virologia , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/patologia , RNA Viral/análise , Evasão Tumoral/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
In Brazil's Atlantic Forest (AF) biodiversity conservation is of key importance since the fungal pathogen Batrachochytrium dendrobatidis (Bd) has led to the rapid loss of amphibian populations here and worldwide. The impact of Bd on amphibians is determined by the host's immune system, of which the skin microbiome is a critical component. The richness and diversity of such cutaneous bacterial communities are known to be shaped by abiotic factors which thus may indirectly modulate host susceptibility to Bd. This study aimed to contribute to understanding the environment-host-pathogen interaction determining skin bacterial communities in 819 treefrogs (Anura: Hylidae and Phyllomedusidae) from 71 species sampled across the AF. We investigated whether abiotic factors influence the bacterial community richness and structure on the amphibian skin. We further tested for an association between skin bacterial community structure and Bd co-occurrence. Our data revealed that temperature, precipitation, and elevation consistently correlate with richness and diversity of the skin microbiome and also predict Bd infection status. Surprisingly, our data suggest a weak but significant positive correlation of Bd infection intensity and bacterial richness. We highlight the prospect of future experimental studies on the impact of changing environmental conditions associated with global change on environment-host-pathogen interactions in the AF.
Assuntos
Batrachochytrium/genética , Microbiota/genética , Micoses/microbiologia , Pele/microbiologia , Animais , Anuros/microbiologia , Batrachochytrium/patogenicidade , Biodiversidade , Brasil , Florestas , Interações entre Hospedeiro e Microrganismos/genéticaRESUMO
Dengue is an acute viral disease caused by Dengue virus (DENV) and is considered to be the most common arbovirus worldwide. The clinical characteristics of dengue may vary from asymptomatic to severe complications and severe organ impairment, particularly affecting the liver. Dengue treatment is palliative with acetaminophen (APAP), usually known as Paracetamol, being the most used drug aiming to relieve the mild symptoms of dengue. APAP is a safe and effective drug but, like dengue, can trigger the development of liver disorders. Given this scenario, it is necessary to investigate the effects of combining these two factors on hepatocyte homeostasis. Therefore, this study aimed to evaluate the molecular changes in hepatocytes resulting from the association between DENV infection and treatment with sub-toxic APAP concentrations. Using an in vitro experimental model of DENV-2 infected hepatocytes (AML-12 cells) treated with APAP, we evaluated the influence of the virus and drug association on the transcriptome of these hepatocytes by RNA sequencing (RNAseq). The virus-drug association was able to induce changes in the gene expression profile of AML-12 cells and here we highlight and explore these changes and its putative influence on biological processes for cellular homeostasis.
Assuntos
Acetaminofen/farmacologia , Analgésicos não Narcóticos/farmacologia , Vírus da Dengue/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Hepatócitos/virologia , Interações entre Hospedeiro e Microrganismos , Transcriptoma , Animais , Linhagem Celular , Homeostase/efeitos dos fármacos , Interações entre Hospedeiro e Microrganismos/efeitos dos fármacos , Interações entre Hospedeiro e Microrganismos/genética , Fígado/citologia , Fígado/efeitos dos fármacos , Fígado/virologia , Camundongos , Análise de Sequência de RNA , Replicação Viral/efeitos dos fármacosRESUMO
Influenza A virus (IAV) activates ZBP1-initiated RIPK3-dependent parallel pathways of necroptosis and apoptosis in infected cells. Although mice deficient in both pathways fail to control IAV and succumb to lethal respiratory infection, RIPK3-mediated apoptosis by itself can limit IAV, without need for necroptosis. However, whether necroptosis, conventionally considered a fail-safe cell death mechanism to apoptosis, can restrict IAV-or indeed any virus-in the absence of apoptosis is not known. Here, we use mice selectively deficient in IAV-activated apoptosis to show that necroptosis drives robust antiviral immune responses and promotes effective virus clearance from infected lungs when apoptosis is absent. We also demonstrate that apoptosis and necroptosis are mutually exclusive fates in IAV-infected cells. Thus, necroptosis is an independent, "stand-alone" cell death mechanism that fully compensates for the absence of apoptosis in antiviral host defense.
Assuntos
Caspase 8/genética , Interações entre Hospedeiro e Microrganismos/genética , Vírus da Influenza A/imunologia , Necroptose/genética , Infecções por Orthomyxoviridae/imunologia , Imunidade Adaptativa , Animais , Apoptose/genética , Apoptose/imunologia , Caspase 8/metabolismo , Feminino , Técnicas de Introdução de Genes , Interações entre Hospedeiro e Microrganismos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Necroptose/imunologia , Infecções por Orthomyxoviridae/virologia , Proteínas de Ligação a RNA/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismoRESUMO
BACKGROUND: Mayaro virus (MAYV) is responsible for a mosquito-borne tropical disease with clinical symptoms similar to dengue or chikungunya virus fevers. In addition to the recent territorial expansion of MAYV, this virus may be responsible for an increasing number of outbreaks. Currently, no vaccine is available. Aedes aegypti is promiscuous in its viral transmission and thus an interesting model to understand MAYV-vector interactions. While the life-cycle of MAYV is known, the mechanisms by which this arbovirus affects mosquito host cells are not clearly understood. METHODS: After defining the best conditions for cell culture harvesting using the highest virus titer, Ae. aegypti Aag-2 cells were infected with a Brazilian MAYV isolate at a MOI of 1 in order to perform a comparative proteomic analysis of MAYV-infected Aag-2 cells by using a label-free semi-quantitative bottom-up proteomic analysis. Time-course analyses were performed at 12 and 48 h post-infection (hpi). After spectrum alignment between the triplicates of each time point and changes of the relative abundance level calculation, the identified proteins were annotated and using Gene Ontology database and protein pathways were annotated using the Kyoto Encyclopedia of Genes and Genomes. RESULTS: After three reproducible biological replicates, the total proteome analysis allowed for the identification of 5330 peptides and the mapping of 459, 376 and 251 protein groups, at time 0, 12 hpi and 48 hpi, respectively. A total of 161 mosquito proteins were found to be differentially abundant during the time-course, mostly related to host cell processes, including redox metabolism, translation, energy metabolism, and host cell defense. MAYV infection also increased host protein expression implicated in viral replication. CONCLUSIONS: To our knowledge, this first proteomic time-course analysis of MAYV-infected mosquito cells sheds light on the molecular basis of the viral infection process and host cell response during the first 48 hpi. Our data highlight several mosquito proteins modulated by the virus, revealing that MAYV manipulates mosquito cell metabolism for its propagation.
Assuntos
Aedes/citologia , Aedes/virologia , Arbovírus/fisiologia , Interações entre Hospedeiro e Microrganismos/genética , Proteômica/métodos , Animais , Arbovírus/genética , Linhagem Celular , Metabolismo Energético , Proteínas de Insetos/análise , Proteínas de Insetos/genética , Mosquitos Vetores/virologia , Replicação ViralRESUMO
Mycobacterium tuberculosis (Mtb) infects alveolar macrophages (AMs), causing pulmonary tuberculosis (PTB), the most common form of the disease. Less frequently, Mtb is disseminated to many other organs and tissues, resulting in different extrapulmonary forms of TB. Nevertheless, very few studies have addressed the global mRNA response of human AMs, particularly from humans with the active form of the disease. Strikingly, almost no studies have addressed the response of human extrapulmonary macrophages to Mtb infection. In this pilot study, using microarray technology, we examined the transcriptomic ex vivo response of AMs from PTB patients (AMTBs) and AMs from control subjects (AMCTs) infected with two clinical isolates of Mtb. Furthermore, we also studied the infection response of human splenic macrophages (SMs) to Mtb isolates, as a model for extrapulmonary infection, and compared the transcriptomic response between AMs and SMs. Our results showed a striking difference in global mRNA profiles in response to infection between AMs and SMs, implicating a tissue-specific macrophage response to Mtb.