Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 17 de 17
Filtrar
Mais filtros











Intervalo de ano de publicação
1.
Plant J ; 117(2): 516-540, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37864805

RESUMO

Bacterial fruit blotch, caused by Acidovorax citrulli, is a serious disease of melon and watermelon. The strains of the pathogen belong to two major genetic groups: group I strains are strongly associated with melon, while group II strains are more aggressive on watermelon. A. citrulli secretes many protein effectors to the host cell via the type III secretion system. Here we characterized AopW1, an effector that shares similarity to the actin cytoskeleton-disrupting effector HopW1 of Pseudomonas syringae and with effectors from other plant-pathogenic bacterial species. AopW1 has a highly variable region (HVR) within amino acid positions 147 to 192, showing 14 amino acid differences between group I and II variants. We show that group I AopW1 is more toxic to yeast and Nicotiana benthamiana cells than group II AopW1, having stronger actin filament disruption activity, and increased ability to induce cell death and reduce callose deposition. We further demonstrated the importance of some amino acid positions within the HVR for AopW1 cytotoxicity. Cellular analyses revealed that AopW1 also localizes to the endoplasmic reticulum, chloroplasts, and plant endosomes. We also show that overexpression of the endosome-associated protein EHD1 attenuates AopW1-induced cell death and increases defense responses. Finally, we show that sequence variation in AopW1 plays a significant role in the adaptation of group I and II strains to their preferred hosts, melon and watermelon, respectively. This study provides new insights into the HopW1 family of bacterial effectors and provides first evidence on the involvement of EHD1 in response to biotic stress.


Assuntos
Citrullus , Comamonadaceae , Cucurbitaceae , Adaptação ao Hospedeiro , Doenças das Plantas/microbiologia , Citrullus/genética , Aminoácidos
2.
Commun Biol ; 6(1): 813, 2023 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-37542124

RESUMO

Insects have a limited host range due to genomic adaptation. Thysanoptera, commonly known as thrips, occupies distinct feeding habitats, but there is a lack of comparative genomic analyses and limited genomic resources available. In this study, the chromosome-level genome of Stenchaetothrips biformis, an oligophagous pest of rice, is assembled using multiple sequencing technologies, including PacBio, Illumina short-reads, and Hi-C technology. A 338.86 Mb genome is obtained, consisting of 1269 contigs with a contig N50 size of 381 kb and a scaffold N50 size of 18.21 Mb. Thereafter, 17,167 protein-coding genes and 36.25% repetitive elements are annotated. Comparative genomic analyses with two other polyphagous thrips, revealing contracted chemosensory-related and expanded stress response and detoxification gene families in S. biformis, potentially facilitating rice adaptation. In the polyphagous thrips species Frankliniella occidentalis and Thrips palmi, expanded gene families are enriched in metabolism of aromatic and anthocyanin-containing compounds, immunity against viruses, and detoxification enzymes. These expansion gene families play crucial roles not only in adapting to hosts but also in development of pesticide resistance, as evidenced by transcriptome results after insecticides treatment. This study provides a chromosome-level genome assembly and lays the foundation for further studies on thrips evolution and pest management.


Assuntos
Tisanópteros , Animais , Tisanópteros/genética , Adaptação ao Hospedeiro , Cromossomos , Genoma , Genômica/métodos
3.
J Infect Dis ; 228(3): 321-331, 2023 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-37254795

RESUMO

BACKGROUND: Nontuberculous mycobacteria (NTM) are ubiquitous in the environment and an increasingly frequent cause of opportunistic infections. Mycobacterium abscessus complex (MABC) is one of the major NTM lung pathogens that disproportionately colonize and infect the lungs of individuals with cystic fibrosis (CF). MABC infection can persist for years, and antimicrobial treatment is frequently ineffective. METHODS: We sequenced the genomes of 175 isolates longitudinally collected from 30 patients with MABC lung infection. We contextualized our cohort amidst the broader MABC phylogeny and investigated genes undergoing parallel adaptation across patients. Finally, we tested the phenotypic consequences of parallel mutations by conducting antimicrobial resistance and mercury-resistance assays. RESULTS: We identified highly related isolate pairs across hospital centers with low likelihood of transmission. We further annotated nonrandom parallel mutations in 22 genes and demonstrated altered macrolide susceptibility co-occurring with a nonsynonymous whiB1 mutation. Finally, we highlighted a 23-kb mercury-resistance plasmid whose loss during chronic infection conferred phenotypic susceptibility to organic and nonorganic mercury compounds. CONCLUSIONS: We characterized parallel genomic processes through which MABC is adapting to promote survival within the host. The within-lineage polymorphisms we observed have phenotypic effects, potentially benefiting fitness in the host at the putative detriment of environmental survival.


Assuntos
Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Humanos , Mycobacterium abscessus/genética , Claritromicina , Adaptação ao Hospedeiro , Infecções por Mycobacterium não Tuberculosas/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Genômica
4.
Acta Trop ; 244: 106951, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37220843

RESUMO

Cystic echinococcosis (CE), caused by Echinococcus granulosus sensu lato, is a neglected tropical disease known mainly for its zoonotic nature. CE is endemic to Pakistan, however, the disease is not given due consideration and millions of people remain at health risk. This study was undertaken to assess the species and genotypes of E. granulosus sensu lato in sheep, buffaloes and cattle, brought to slaughterhouses of two major cities (Multan and Bahawalpur) of south Punjab, Pakistan. A total of 26 hydatid cyst specimens were characterized through complete cox1 mitochondrial gene (1609 bp) sequencing. Species and genotypes of E. granulosus sensu lato discovered in the southern Punjab consisted of E. granulosus sensu stricto (n =21), E. ortleppi (n=4) and genotype G6 of the E. canadensis cluster (n=1). Of E. granulosus s.s. isolates, the genotype G3 was predominantly involved in causing infections to the livestock of this region. Since all of these species are zoonotic, wide and effective surveillance studies are required to ascertain the risks to human population in Pakistan. Additionally, a global overview on cox1 phylogenetic structure of E. ortleppi was carried out. Despite widespread occurrence, the species is mostly limited to the southern hemisphere. The highest burden has been reported in South America (62.15%) and Africa (28.44%) and by far the most common host is cattle, accounting for >90% of cases.


Assuntos
Equinococose , Echinococcus granulosus , Echinococcus , Humanos , Animais , Bovinos , Ovinos , Echinococcus/genética , Paquistão , Adaptação ao Hospedeiro , Filogenia , Echinococcus granulosus/genética , Equinococose/epidemiologia , Genótipo , Genes Mitocondriais , Búfalos
5.
Analyst ; 147(23): 5546-5556, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36342038

RESUMO

Complexation of the glutamic-tyrosine-glutamic tripeptide (EYE) with a series of pseudopeptidic cages has been thoroughly investigated using different analytical techniques. The stoichiometry and affinities of the supramolecular host : guest complexes both in aqueous solution and in the gas-phase were obtained from a suitable combination of fluorescence spectroscopy, NMR, and mass spectrometry (MS) methods. The cages bearing basic groups (lysine, ornitine and histidine) display the tightest EYE binding in aqueous media following the order CyHis > CyLys > CyOrn, thus suggesting that Tyr side chain encapsulation is additionally modulated by the identity of the cage side chains and their ability to be engaged in polar interactions with the EYE peptide. Similarly, binding affinities estimated by MS methods clearly point towards a reduced affinity for the Cy cages with acidic pendant groups and a higher affinity of the CyHis cage over CyLys and CyOrn. Ion mobility spectrometry (IMS)-MS, assisted by molecular modelling, has been used to uncover the structural and conformational characteristics of the pseudopeptidic hosts and their supramolecular adducts with the EYE peptide. The cages display a collisional cross-section increase upon EYE inclusion that is associated with the expansion of the binding pocket of the cage cavity, thus constituting a unique example of conformational pseudopeptidic host adaptation to accommodate the inclusion of the guest.


Assuntos
Adaptação ao Hospedeiro , Espectrometria de Mobilidade Iônica , Peptídeos/química , Conformação Molecular , Tirosina/química , Espectrometria de Massas
6.
Science ; 378(6617): 290-295, 2022 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-36264814

RESUMO

Adaptations to infectious and dietary pressures shape mammalian physiology and disease risk. How such adaptations affect sex-biased diseases remains insufficiently studied. In this study, we show that sex-dependent hepatic gene programs confer a robust (~300%) survival advantage for male mice during lethal bacterial infection. The transcription factor B cell lymphoma 6 (BCL6), which masculinizes hepatic gene expression at puberty, is essential for this advantage. However, protection by BCL6 protein comes at a cost during conditions of dietary excess, which result in overt fatty liver and glucose intolerance in males. Deleting hepatic BCL6 reverses these phenotypes but markedly lowers male survival during infection, thus establishing a sex-dependent trade-off between host defense and metabolic systems. Our findings offer strong evidence that some current sex-biased diseases are rooted in ancient evolutionary trade-offs between immunity and metabolism.


Assuntos
Infecções Bacterianas , Evolução Biológica , Fígado Gorduroso , Adaptação ao Hospedeiro , Fígado , Proteínas Proto-Oncogênicas c-bcl-6 , Animais , Masculino , Camundongos , Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Regulação da Expressão Gênica , Fígado/metabolismo , Adaptação ao Hospedeiro/genética , Adaptação ao Hospedeiro/imunologia , Proteínas Proto-Oncogênicas c-bcl-6/genética , Proteínas Proto-Oncogênicas c-bcl-6/fisiologia , Deleção de Genes , Fatores Sexuais , Infecções Bacterianas/genética , Infecções Bacterianas/imunologia
7.
Viruses ; 14(2)2022 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-35215875

RESUMO

Chikungunya virus (CHIKV) is an emerging arthropod-borne virus that has spread globally during the last two decades. The virus is mainly transmitted by Aedes aegypti and Aedes albopictus mosquitos and is thus capable of replicating in both human and mosquito cells. CHIKV has a broad tropism in vivo, capable of replicating in various tissues and cell types but largely excluding blood cells. This was reflected in vitro by a broad array of adherent cell lines supporting CHIKV infection. One marked exception to this general rule is the resistance of the lung cancer-derived A549 cell line to CHIKV infection. We verified that A549 cells were restrictive to infection by multiple alphaviruses while being completely permissive to flavivirus infection. The adaptive growth of a primary CHIKV strain through multiple passages allowed the emergence of a CHIKV strain that productively infected A549 cells while causing overt cytopathic effects and without a fitness cost for replication in otherwise CHIKV-susceptible cells. Whole genome sequencing of polyclonal and monoclonal preparations of the adapted virus showed that a limited number of mutations consistently emerged in both structural (2 mutations in E2) and non-structural proteins (1 mutation in nsP1 and 1 mutation in nsP2). The introduction of the adaptive mutations, individually or in combinations, into a wild-type molecular clone of CHIKV allowed us to determine the relative contributions of the mutations to the new phenotype. We found that the mutations in the E2 envelope protein and non-structural proteins contributed significantly to the acquired phenotype. The nsP mutations were introduced in a split-genome trans-replicase assay to monitor their effect on viral genome replication efficiency. Interestingly, neither mutation supported increased viral genomic replication in either Vero or A549 cells.


Assuntos
Adaptação Fisiológica , Vírus Chikungunya/fisiologia , Genoma Viral , Adaptação ao Hospedeiro , Proteínas do Envelope Viral/genética , Proteínas não Estruturais Virais/genética , Células A549 , Animais , Vírus Chikungunya/genética , Chlorocebus aethiops , Efeito Citopatogênico Viral , Humanos , Mutação , Fenótipo , Células Vero , Tropismo Viral , Ligação Viral , Replicação Viral
8.
Int J Mol Sci ; 22(19)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34638623

RESUMO

How herbivorous insects adapt to host plants is a key question in ecological and evolutionary biology. The fall armyworm, (FAW) Spodoptera frugiperda (J.E. Smith), although polyphagous and a major pest on various crops, has been reported to have a rice and corn (maize) feeding strain in its native range in the Americas. The species is highly invasive and has recently established in China. We compared behavioral changes in larvae and adults of a corn population (Corn) when selected on rice (Rice) and the molecular basis of these adaptational changes in midgut and antennae based on a comparative transcriptome analysis. Larvae of S. frugiperda reared on rice plants continuously for 20 generations exhibited strong feeding preference for with higher larval performance and pupal weight on rice than on maize plants. Similarly, females from the rice selected population laid significantly more eggs on rice as compared to females from maize population. The most highly expressed DEGs were shown in the midgut of Rice vs. Corn. A total of 6430 DEGs were identified between the populations mostly in genes related to digestion and detoxification. These results suggest that potential adaptations for feeding on rice crops, may contribute to the current rapid spread of fall armyworm on rice crops in China and potentially elsewhere. Consistently, highly expressed DEGs were also shown in antennae; a total of 5125 differentially expressed genes (DEGs) s were identified related to the expansions of major chemosensory genes family in Rice compared to the Corn feeding population. These results not only provide valuable insight into the molecular mechanisms in host plants adaptation of S. frugiperda but may provide new gene targets for the management of this pest.


Assuntos
Spodoptera/genética , Spodoptera/fisiologia , Adaptação Fisiológica/genética , Animais , China , Produtos Agrícolas/parasitologia , Fenômenos Fisiológicos do Sistema Digestório , Comportamento Alimentar/fisiologia , Feminino , Ontologia Genética , Genes de Insetos , Herbivoria/genética , Herbivoria/fisiologia , Adaptação ao Hospedeiro/genética , Adaptação ao Hospedeiro/fisiologia , Especificidade de Hospedeiro/genética , Especificidade de Hospedeiro/fisiologia , Interações Hospedeiro-Parasita/genética , Interações Hospedeiro-Parasita/fisiologia , Larva/fisiologia , Masculino , Oryza/parasitologia , Oviposição/fisiologia , Spodoptera/patogenicidade , Transcriptoma , Zea mays/parasitologia
9.
Rev. biol. trop ; 69(3)sept. 2021.
Artigo em Espanhol | LILACS, SaludCR | ID: biblio-1387664

RESUMO

Resumen Introducción: La relación parásito-hospedero entre Dendroctonus y Pinus es reconocida como una amenaza importante para los bosques de coníferas, debido a que puede causar una alta mortalidad de árboles y consecuentemente una pérdida de cobertura forestal. Objetivo: Identificar potenciales interacciones parásito-huésped entre descortezadores y pinos, así como la contribución de las condiciones ambientales para el establecimiento de estas interacciones ecológicas. Métodos: Se realizaron modelos de nicho ecológico y análisis de redes ecológicas con la plataforma web de minería de datos espaciales SPECIES (http://species.conabio.gob.mx/). Se incluyeron siete especies de descortezadores, 52 de pinos y 19 variables bioclimáticas del portal WorldClim. Resultados: Se identificaron 140 interacciones potenciales, de las cuales el 42 % no han sido registradas previamente. El análisis de redes ecológicas nos permitió caracterizar las relaciones parásito-hospedero en generalistas y especialistas. En cuanto al análisis de nicho ecológico, se determinó la distribución potencial de los descortezadores combinando las distribuciones de Pinus y variables climáticas como predictores. Se observó que las variables climáticas contribuyen de forma negativa para la mayoría de las especies de Dendroctonus, es decir, estas variables son restrictivas en casi toda su distribución, por el contrario, las variables bióticas (Pinus) fueron positivas e informativas sobre la mayoría de las distribuciones. Conclusiones: Los patrones de coexistencia de descortezadores y pinos nos proporcionan información sobre las interacciones que se pueden establecer entre estas especies y que hasta hoy pueden ser desconocidas. Además, la integración de factores bióticos (hospederos) y abióticos (clima), permite obtener modelos de distribución geográfica que caracteriza las regiones con condiciones favorables para la presencia de las especies, así como las especies de hospederos con los que podrían estar interactuando en dichas regiones. Considerando el riesgo fitosanitario por descortezadores, nuestros resultados brindan escenarios geográficos y ecológicos de riesgo donde infestaciones por descortezadores podrían darse, así como la posible emergencia de nuevas interacciones parásito-hospedero desconocidas hasta hoy. Estos modelos son una herramienta que en el futuro pueden dirigir esfuerzos de trabajo de campo para validar y complementar nuestros resultados.


Abstract Introduction: The parasite-host relationship between bark beetles of the genus Dendroctonus and species of the genus Pinus has been recognized as important threat to coniferous forests because it can cause high tree mortality and therefore a loss of forests. Objectives: We aimed to identify the potential unknown parasite-host relationships among bark beetles and pine trees species, as well as the contribution of environmental conditions as driver of these ecological interactions. Methods: We carried out ecological niche models and ecological network analysis using the spatial datamining platform SPECIES (http://species.conabio.gob.mx/). Our study included seven species of bark beetles, 52 species of the genus Pinus, and 19 bioclimatic variables from Worldclim dataset. Results: We identified 140 potential interactions between Dendroctonus and Pinus species, of which 42 % have not been previously registered. Complex inference network analysis allowed us to characterize ecological parasite-host interactions in generalists and specialists. Regarding the ecological niche analysis, we determined potential bark beetle distributions by combining Pinus species ranges and climatic variables as predictors. We noted that climatic variables contributed negatively to Dendroctonus distribution for the most species, i.e. these abiotic variables are restrictive in almost the entire distribution of the beetles; conversely, biotic variables (i.e. Pinus species) were positive and informative on the most of species ranges. Conclusions: Coexistence patterns of bark beetles and Pinus provide us information on the interactions that are able to establish among these species and that until now can be unknown. In addition, integrating biotic (hosts) and abiotic (climate) factors, allows us to obtain geographic distribution models that characterize the regions with favorable conditions for the presence of bark beetles, as well as the host species with which they could be interacting in those regions. Considering the phytosanitary risk due to bark beetles, our results provide geographic and ecological scenarios where bark beetles infestations may occur, as well as the possible emergence of new parasite-host interactions. These models can be a tool to address future fieldwork efforts to validate and complement our results.


Assuntos
Animais , Besouros , Adaptação ao Hospedeiro , México
10.
PLoS Biol ; 19(4): e3001201, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33872300

RESUMO

Most vertebrate RNA viruses show pervasive suppression of CpG and UpA dinucleotides, closely resembling the dinucleotide composition of host cell transcriptomes. In contrast, CpG suppression is absent in both invertebrate mRNA and RNA viruses that exclusively infect arthropods. Arthropod-borne (arbo) viruses are transmitted between vertebrate hosts by invertebrate vectors and thus encounter potentially conflicting evolutionary pressures in the different cytoplasmic environments. Using a newly developed Zika virus (ZIKV) model, we have investigated how demands for CpG suppression in vertebrate cells can be reconciled with potentially quite different compositional requirements in invertebrates and how this affects ZIKV replication and transmission. Mutant viruses with synonymously elevated CpG or UpA dinucleotide frequencies showed attenuated replication in vertebrate cell lines, which was rescued by knockout of the zinc-finger antiviral protein (ZAP). Conversely, in mosquito cells, ZIKV mutants with elevated CpG dinucleotide frequencies showed substantially enhanced replication compared to wild type. Host-driven effects on virus replication attenuation and enhancement were even more apparent in mouse and mosquito models. Infections with CpG- or UpA-high ZIKV mutants in mice did not cause typical ZIKV-induced tissue damage and completely protected mice during subsequent challenge with wild-type virus, which demonstrates their potential as live-attenuated vaccines. In contrast, the CpG-high mutants displayed enhanced replication in Aedes aegypti mosquitoes and a larger proportion of mosquitoes carried infectious virus in their saliva. These findings show that mosquito cells are also capable of discriminating RNA based on dinucleotide composition. However, the evolutionary pressure on the CpG dinucleotides of viral genomes in arthropod vectors directly opposes the pressure present in vertebrate host cells, which provides evidence that an adaptive compromise is required for arbovirus transmission. This suggests that the genome composition of arbo flaviviruses is crucial to maintain the balance between high-level replication in the vertebrate host and persistent replication in the mosquito vector.


Assuntos
Evolução Molecular , Genoma Viral/genética , Interações Hospedeiro-Patógeno/genética , Zika virus/genética , Células A549 , Aedes/virologia , Animais , Composição de Bases/fisiologia , Sequência de Bases/genética , Linhagem Celular , Chlorocebus aethiops , Ilhas de CpG/fisiologia , Fosfatos de Dinucleosídeos/análise , Fosfatos de Dinucleosídeos/genética , Adaptação ao Hospedeiro/genética , Humanos , Masculino , Mamíferos/virologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mosquitos Vetores/genética , Mosquitos Vetores/virologia , RNA Viral/química , RNA Viral/genética , Seleção Genética/fisiologia , Células Vero , Infecção por Zika virus/genética , Infecção por Zika virus/transmissão , Infecção por Zika virus/virologia
11.
Elife ; 102021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33752799

RESUMO

Immunity to malaria is often considered slow to develop but this only applies to defense mechanisms that function to eliminate parasites (resistance). In contrast, immunity to severe disease can be acquired quickly and without the need for improved pathogen control (tolerance). Using Plasmodium chabaudi, we show that a single malaria episode is sufficient to induce host adaptations that can minimise inflammation, prevent tissue damage and avert endothelium activation, a hallmark of severe disease. Importantly, monocytes are functionally reprogrammed to prevent their differentiation into inflammatory macrophages and instead promote mechanisms of stress tolerance to protect their niche. This alternative fate is not underpinned by epigenetic reprogramming of bone marrow progenitors but appears to be imprinted within the remodelled spleen. Crucially, all of these adaptations operate independently of pathogen load and limit the damage caused by malaria parasites in subsequent infections. Acquired immunity to malaria therefore prioritises host fitness over pathogen clearance.


Malaria is a parasitic infection spread by mosquitoes that causes hundreds of millions of cases each year. People are most likely to die from malaria the first time they are infected ­ usually when they are young children. Among those who survive, however, few will develop severe symptoms again, even though they are often reinfected with as many (or even more) parasites. This indicates that people do not get better at eliminating the parasite. Instead, protection from severe malaria is a form of tolerance - the body learns to limit the damage the infection causes. But exactly which mechanisms have to be engaged to tolerate malaria is unclear. One way to achieve tolerance may be to switch off damaging inflammation. Nahrendorf et al. explored this possibility by comparing the immune response of mice to their first and second infection with malaria parasites. During the first infection of life, immune cells release harmful inflammatory molecules that activate the lining of blood vessels, causing tissue damage and severe symptoms. During the second infection, these immune cells shut down inflammation and instead actively promote tissue health to reduce damage and improve outcome. This change in the immune response occurs despite the fact that the number of parasites is the same in both infections. Nahrendorf et al. also found that the mouse's immune cells 'remembered' to tolerate subsequent infections, even after treatment with a drug that kills all malaria parasites. This was possible because malaria permanently altered the spleen, which reprogrammed the response of the immune cells. A single infection is therefore enough to induce long-lived mechanisms of tolerance that can prevent life-threatening disease. These findings have the potential to change the understanding of immunity to malaria, which currently emphasises the importance of killing parasites. New ways to treat and vaccinate people - and to protect young children from severe malaria - may arise by treating tolerance as an equally important form of host defense.


Assuntos
Imunidade Adaptativa/imunologia , Malária/imunologia , Animais , Adaptação ao Hospedeiro , Interações Hospedeiro-Parasita/imunologia , Humanos , Tolerância Imunológica , Inflamação/imunologia , Macrófagos/imunologia , Malária/parasitologia , Malária Falciparum/imunologia , Malária Falciparum/parasitologia , Monócitos/imunologia , Mielopoese/imunologia , Plasmodium chabaudi/fisiologia , Plasmodium falciparum/fisiologia , Baço/imunologia
12.
PLoS Pathog ; 16(12): e1009177, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33370400

RESUMO

HIV-1 strains harboring immune escape mutations can persist in circulation, but the impact of selection by multiple HLA alleles on population HIV-1 dynamics remains unclear. In Japan, HIV-1 Reverse Transcriptase codon 135 (RT135) is under strong immune pressure by HLA-B*51:01-restricted and HLA-B*52:01-restricted T cells that target a key epitope in this region (TI8; spanning RT codons 128-135). Major population-level shifts have occurred at HIV-1 RT135 during the Japanese epidemic, which first affected hemophiliacs (via imported contaminated blood products) and subsequently non-hemophiliacs (via domestic transmission). Specifically, threonine accumulated at RT135 (RT135T) in hemophiliac and non-hemophiliac HLA-B*51:01+ individuals diagnosed before 1997, but since then RT135T has markedly declined while RT135L has increased among non-hemophiliac individuals. We demonstrated that RT135V selection by HLA-B*52:01-restricted TI8-specific T-cells led to the creation of a new HLA-C*12:02-restricted epitope TN9-8V. We further showed that TN9-8V-specific HLA-C*12:02-restricted T cells selected RT135L while TN9-8T-specific HLA-C*12:02-restricted T cells suppressed replication of the RT135T variant. Thus, population-level accumulation of the RT135L mutation over time in Japan can be explained by initial targeting of the TI8 epitope by HLA-B*52:01-restricted T-cells, followed by targeting of the resulting escape mutant by HLA-C*12:02-restricted T-cells. We further demonstrate that this phenomenon is particular to Japan, where the HLA-B*52:01-C*12:02 haplotype is common: RT135L did not accumulate over a 15-year longitudinal analysis of HIV sequences in British Columbia, Canada, where this haplotype is rare. Together, our observations reveal that T-cell responses to sequentially emerging viral escape mutants can shape long-term HIV-1 population dynamics in a host population-specific manner.


Assuntos
Variação Antigênica/imunologia , Infecções por HIV , HIV-1 , Evasão da Resposta Imune/genética , Linfócitos T Citotóxicos/imunologia , Células Cultivadas , Evolução Clonal/imunologia , Epitopos de Linfócito T/genética , Infecções por HIV/imunologia , Infecções por HIV/virologia , Soropositividade para HIV , HIV-1/classificação , HIV-1/genética , HIV-1/imunologia , Células HeLa , Adaptação ao Hospedeiro/imunologia , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Tipagem Molecular , Mutação , Linfócitos T Citotóxicos/metabolismo , Carga Viral/imunologia , Replicação Viral/genética , Replicação Viral/imunologia
13.
J Gen Virol ; 101(11): 1170-1181, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32857690

RESUMO

Border disease virus (BDV) envelope glycoprotein E2 is required for entry into cells and is a determinant of host tropism for sheep and pig cells. Here, we describe adaptive changes in the BDV E2 protein that modify virus replication in pig cells. To achieve this, two BDV isolates, initially collected from a pig and a sheep on the same farm, were passaged in primary sheep and pig cells in parallel with a rescued variant of the pig virus derived from a cloned full-length BDV cDNA. The pig isolate and the rescued virus shared the same amino acid sequence, but the sheep isolate differed at ten residues, including two substitutions in E2 (K771E and Y925H). During serial passage in cells, the viruses displayed clear selectivity for growth in sheep cells; only the cDNA-derived virus adapted to grow in pig cells. Sequencing revealed an amino acid substitution (Q739R) in the E2 domain DA of this rescued virus. Adaptation at the same residue (Q739K/Q739R) was also observed after passaging of the pig isolate in sheep cells. Use of reverse genetics confirmed that changing residue Q739 to R or K (each positively charged) was sufficient to achieve adaptation to pig cells. Furthermore, this change in host tropism was suppressed if Q739R was combined with K771E. Another substitution (Q728R), conferring an additional positive charge, acquired during passaging, restored the growth of the Q739R/K771E variant. Overall, this study provided evidence that specific, positively charged, residues in the E2 domain DA are crucial for pig-cell tropism of BDV.


Assuntos
Vírus da Doença da Fronteira/química , Vírus da Doença da Fronteira/crescimento & desenvolvimento , Adaptação ao Hospedeiro , Ovinos/virologia , Suínos/virologia , Proteínas Estruturais Virais/química , Adaptação Fisiológica , Sequência de Aminoácidos , Substituição de Aminoácidos , Animais , Vírus da Doença da Fronteira/genética , Células Cultivadas , DNA Complementar , DNA Viral/genética , Especificidade de Hospedeiro , Modelos Moleculares , Conformação Proteica , Domínios Proteicos , Inoculações Seriadas , Proteínas Estruturais Virais/genética , Tropismo Viral
14.
Cell Host Microbe ; 28(4): 534-547.e3, 2020 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-32755549

RESUMO

Pseudomonas aeruginosa and Burkholderia cepacia complex (Bcc) species are opportunistic lung pathogens of cystic fibrosis (CF) patients. While P. aeruginosa can initiate long-term infections in younger CF patients, Bcc infections only arise in teenagers and adults. Both P. aeruginosa and Bcc use type VI secretion systems (T6SSs) to mediate interbacterial competition. Here, we show P. aeruginosa isolates from teenage and adult CF patients, but not those from young CF patients, are outcompeted by the epidemic Bcc isolate Burkholderia cenocepacia strain AU1054 in a T6SS-dependent manner. The genomes of susceptible P. aeruginosa isolates harbor T6SS-abrogating mutations, the repair of which, in some cases, rendered the isolates resistant. Moreover, seven of eight Bcc strains outcompeted P. aeruginosa strains isolated from the same patients. Our findings suggest certain mutations that arise as P. aeruginosa adapts to the CF lung abrogate T6SS activity, making P. aeruginosa and its human host susceptible to potentially fatal Bcc superinfection.


Assuntos
Complexo Burkholderia cepacia/fisiologia , Coinfecção/microbiologia , Adaptação ao Hospedeiro/fisiologia , Interações Hospedeiro-Patógeno/fisiologia , Pseudomonas aeruginosa/metabolismo , Sistemas de Secreção Tipo VI/metabolismo , Adolescente , Adulto , Animais , Infecções por Burkholderia/microbiologia , Complexo Burkholderia cepacia/isolamento & purificação , Criança , Pré-Escolar , Fibrose Cística/microbiologia , Humanos , Lactente , Pulmão/microbiologia , Mutação , Infecções por Pseudomonas , Pseudomonas aeruginosa/isolamento & purificação , Sistemas de Secreção Tipo VI/genética , Adulto Jovem
15.
Front Immunol ; 11: 793, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32477336

RESUMO

Starting at birth, newborn infants are exposed to numerous microorganisms. Adaptation of the innate immune system to them is a delicate process, with potentially advantageous and harmful implications for health development. Cytomegaloviruses (CMVs) are highly adapted to their specific mammalian hosts, with which they share millions of years of co-evolution. Throughout the history of mankind, human CMV has infected most infants in the first months of life without overt implications for health. Thus, CMV infections are intertwined with normal immune development. Nonetheless, CMV has retained substantial pathogenicity following infection in utero or in situations of immunosuppression, leading to pathology in virtually any organ and particularly the central nervous system (CNS). CMVs enter the host through mucosal interfaces of the gastrointestinal and respiratory tract, where macrophages (MACs) are the most abundant immune cell type. Tissue MACs and their potential progenitors, monocytes, are established target cells of CMVs. Recently, several discoveries have revolutionized our understanding on the pre- and postnatal development and site-specific adaptation of tissue MACs. In this review, we explore experimental evidences and concepts on how CMV infections may impact on MAC development and activation as part of host-virus co-adaptation.


Assuntos
Infecções por Citomegalovirus/imunologia , Citomegalovirus/imunologia , Imunidade Inata , Imunidade nas Mucosas , Macrófagos/imunologia , Animais , Infecções por Citomegalovirus/virologia , Adaptação ao Hospedeiro/imunologia , Humanos , Imunomodulação , Lactente , Recém-Nascido , Camundongos , Monócitos/imunologia
16.
Rev. argent. microbiol ; 48(3): 206-209, set. 2016. ilus
Artigo em Inglês | LILACS | ID: biblio-1290559

RESUMO

Se estudió el rol prospectivo de Rumina decollata como potencial hospedador paraténico de Toxocara cati para los gatos domésticos. Se recolectaron caracoles R. decollata y heces de gatos de un hospital de la Ciudad Autónoma de Buenos Aires. Se procesaron las heces y los caracoles fueron digeridos para identificar estadios de T. cati por análisis morfológico y molecular. El 23,5% (4/17) de las muestras de heces resultaron positivas a huevos larvados de T. cati. El 20% (5/25) de los pooles de caracoles fue positivo a larvas de tercer estadío (L3) de Toxocara spp. por PCR. El promedio de larvas totales recuperadas por gramo de caracol en todos los pooles positivos fue de 5.1, con un máximo de 33 L3/pool. Se trata del primer reporte de R. decollata como hospedador paraténico de T. cati, puesto que ha sido demostrada la infección en caracoles y gatos en un ambiente común


The prospective role of the land snail Rumina decollata as a potential paratenic host of Toxocara cati for domestic cats was studied. R. decollata specimens and cats' feces were collected from the open spaces of a Buenos Aires city hospital. Cats' feces were analyzed and snails were digested to identify T. cati stages, by morphological and molecular analyses. T. cati larval eggs were recovered from 23.5% (4/17) of the sampled feces. Twenty percent of snail pools (5/25) were confirmed to be positive for Toxocara spp. third larval stage (L3) by PCR. The mean value of total larvae recovered per gram of snail in all positive pools was 5.1, with a maximum 33 L3/pool. This is the first report of T. cati infective larvae in R. decollata domestic snail as a paratenic host, since the relationship between infection in snails and in cats' feces could be demonstrated in a common environment


Assuntos
Animais , Gatos , Caramujos/parasitologia , Caramujos/patogenicidade , Toxocara/isolamento & purificação , Reação em Cadeia da Polimerase/métodos , Fezes/parasitologia , Adaptação ao Hospedeiro/fisiologia
17.
Rev. biol. trop ; 63(2): 341-356, Apr.-Jun. 2015. graf, tab
Artigo em Inglês | LILACS, SaludCR | ID: lil-764971

RESUMO

Despite the ubiquity and importance of indigenous arbuscular mycorrhizal fungi (AMF) for plant ecosystems; functioning of indigenus mycorrhizal symbiosis (IMS) and related environmental factors at coastal Caribbean ecosystems remains still scarce. In order to determine functionality of IMS under contrasting land uses and wet seasons from Cuba, the influence of the water stress on some AMF functionality parameters from a semi-natural savannah (NS), a recovered savannah (RS) and an agro-ecosystem (AG) from the Managed Floristic Reserve San Ubaldo-Sabanalamar, Pinar del Rio, Cuba were assessed during two-years. Soil and root samples were collected in April and October, during the dry and wet seasons, respectively, in 2008 and 2010. Four plots in each ecosystem were selected, and five soil sub-samples were randomly collected, bulked, mixed homogeneously and used as the composite sample per plot. The host plant root biomass, arbuscular mycorrhizal colonization of the host plant, density of the intraradical and extraradical AMF mycelia, fungal endophyte biomass and AMF spore density were assessed. The host plant root biomass increased in the NS environment during the dry season, and approximately 12.85g root/dm³ dry soil was recorded. The colonization degree were significantly higher in all environments during the wet season of the second year, with means ranging from 79% to 89%. The extraradical mycelia were significantly more abundant in the dry season of the second year in all environments, with a maximum of 279mg/dm³ in the RS ecosystem. The density of AMF spores was highest in the dry season of the second year for the three studied ecosystems. The RS ecosystem hosted 5 670 spores/100g dry soil. In general, the influence of rainfall seasonality on the function of AMF was stronger than the influence of ecosystem management. The root biomass and extraradical mycelia were high in the dry seasons, suggesting strategies to increase the volume of soil for the mutual benefit of the symbionts. The increase in spore density during the dry seasons appears as an adaptation allowing AMF to survive period of water shortage. This study improves our understanding of the adaptative responses of arbuscular mycorrhizal symbiosis to seasonal variations in soil water availability. Rev. Biol. Trop. 63 (2): 341-356. Epub 2015 June 01.


En el presente estudio se evaluó, durante dos años, la influencia de los períodos seco y lluvioso sobre el funcionamiento de hongos formadores de micorrizas arbusculares (HFMA) simbiontes de plantas nativas de una sabana semi natural, una sabana recuperada de la actividad agrícola y un agroecosistema, ubicados en la Reserva Florística Manejada San Ubaldo-Sabanalamar, Pinar del Río, Cuba. Se recolectaron muestras de suelo en abril y octubre (período seco y húmedo de 2008 y 2010, respectivamente). Dentro de cada ecosistema se seleccionaron cuatro parcelas y se recolectaron cinco submuestras al azar, las que fueron homogeneizadas para formar una muestra compuesta por parcela. Se cuantificó la biomasa de raicillas, la colonización micorrízica de las plantas hospedadoras en el campo, el micelio extrarradical, el micelio endófito y la densidad de esporas. La biomasa de raicillas en la sabana semi natural incrementó durante los períodos secos, la cual alcanzó hasta 12.85 g/dm3 de suelo. En todos los ecosistemas, la mayor colonización micorrízica ocurrió en la época lluviosa del segundo año con valores que oscilaron entre 79 y 89 %. Las mayores biomasas de micelio externo fueron registradas en los tres ecosistemas durante el período seco del segundo año, con un valor máximo de 279 mg/dm3 de suelo en la sabana recuperada. La mayor densidad de esporas de HFMA fue determinada en el periodo seco del segundo año para los tres ecosistemas estudiados, con el valor más alto en la sabana recuperada con 5 670 esporas/100 g de suelo seco. De manera general, se evidenció un efecto de la estacionalidad de la lluvia más que del manejo de ecosistema sobre el funcionamiento de los HFMA. La mayor actividad colonizadora se evidenció en períodos húmedos, mientras que mayor biomasa de raicillas y micelio externo durante los períodos secos, lo que sugiere estrategias de incremento del volumen del suelo explorado por parte de los HFMA como de las plantas hospedadoras. La proliferación de esporas evidenció la formación de estructuras de resistencia de los HFMA ante condiciones adversas. Los resultados obtenidos pondrían en evidencia la plasticidad de la simbiosis micorrízica ante variaciones en la disponibilidad de agua.


Assuntos
Micorrizas/crescimento & desenvolvimento , Fungos/classificação , Cuba , Adaptação ao Hospedeiro
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA