RESUMO
BACKGROUND: There is equivocal evidence about beneficial properties of omega-3 long-chain polyunsaturated fatty acids (ω-3 LCPUFA) for older adults. OBJECTIVE: This study investigated the relationship between circulating ω-3 LCPUFA, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) levels and their corresponding dietary intakes with cognition and physical function in a cohort of community-dwelling older adults at risk of dementia. METHODS: A cross-sectional analysis was conducted among 142 community-dwelling older adults (60-85 years) with subjective memory complaints. Erythrocyte fatty acids (ω-3 LCPUFA) and the omega-3 index were measured; dietary DHA and EPA were assessed with a LCPUFA specific questionnaire. Cognition was measured using the Cogstate computerised battery and Trail-making tests. Muscle strength was assessed by grip strength and physical function via the four-square step test, 30-second sit-to-stand, timed up-and-go test, and 4-m walk test. Multiple regression analysis was used to assess the relationship between erythrocyte ω-3 LCPUFA, dietary intake, cognitive and physical function. RESULTS: Higher dietary DHA and EPA were associated with better global cognitive function (DHA: ß=0.164, p=0.042; EPA: ß=0.188, p=0.020). Higher dietary EPA was associated with better attention/psychomotor composite scores (ß=0.196, p=0.024), mobility (four-square step test: ß=-0.202, p=0.015) and gait speed (4m walk test: ß=-0.200, p=0.017). No associations were found between erythrocyte ω-3 LCPUFA and cognitive or functional performance measures. CONCLUSIONS: In community-dwelling older adults with subjective memory complaints, higher dietary ω-3 LCPUFA intake was associated with better cognitive and physical function, supporting the evidence that ω-3 fatty acids play a role in optimising physical and cognitive health during ageing.
Assuntos
Cognição/efeitos dos fármacos , Ácidos Graxos Ômega-3/sangue , Saúde/normas , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The present study aimed to develop a food frequency questionnaire (FFQ) assessing dietary omega-3 long chain polyunsaturated fatty acid (n-3 LCPUFA) intake in Australian children and to validate the FFQ against a 7-day food diary. METHODS: The investigation comprised a cross-sectional and validation study. The study setting was two private primary schools in the in the Illawarra region of New South Wales. Twenty-two Australian children, aged 9-13 years, who were not on a special diet or receiving medical care that limited their food choice in the 3 months prior to recruitment, were recruited into the study. RESULTS: A total of 131 items, classified according to seven food group categories, was included in the n-3 LCPUFA FFQ, as identified from published dietary surveys and a supermarket survey. Good correlations between the FFQ and the 7-day food diary were observed for eicosapentaenoic acid (EPA) [r = 0.691, 95% confidence interval (CI) = 0.51-0.83, P < 0.001], docosahexaenoic acid (DHA) (r = 0.684, 95% CI = 0.45-0.84, P < 0.001) and total n-3 LCPUFA (r = 0.687, 95% CI = 0.48-0.85, P < 0.001). Bland-Altman plots showed an acceptable limit of agreement between the FFQ and the average 7-day food diary. However, the mean EPA, DHA and total n-3 LCPUFA intakes estimated from the FFQ were significantly higher than those from the average 7-day food diary estimates (P < 0.001). CONCLUSIONS: A novel n-3 LCPUFA FFQ that has been developed to estimate dietary n-3 LCPUFA intakes in Australian children has been shown to have relative validity. The FFQ provides a useful contribution to dietary assessment methodology in this age group; however, reproducibility remains to be demonstrated.
Assuntos
Inquéritos sobre Dietas , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácido Eicosapentaenoico/administração & dosagem , Ácidos Graxos Insaturados/administração & dosagem , Avaliação Nutricional , Adolescente , Austrália , Criança , Estudos Transversais , Dieta , Registros de Dieta , Feminino , Humanos , Masculino , Projetos Piloto , Reprodutibilidade dos TestesRESUMO
High-fat diet (HFD) induces obesity. This study examined the effects of Shiitake mushroom on the prevention of alterations of plasma lipid profiles, fat deposition, energy efficiency, and body fat index induced by HFD. Rats were given a low, medium, and high (7, 20, 60 g/kg = LD-M, MD-M, HD-M) Shiitake mushroom powder in their high-fat (50% in kcal) diets for 6 weeks. The results showed that the rats on the HD-M diet had the lowest body weight gain compared to MD-M and LD-M groups (P < 0.05). The total fat deposition was significantly lower (-35%, P < 0.05) in rats fed an HD-M diet than that of HFD group. Interestingly, plasma triacylglycerol (TAG) level was significantly lower (-55%, P < 0.05) in rats on HD-M than HFD. This study also revealed the existence of negative correlations between the amount of Shiitake mushroom supplementation and body weight gain, plasma TAG, and total fat masses.
RESUMO
The health benefits attributed to the consumption of long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) are enormous but are we consuming enough for optimal health? Cardiovascular disease rates are much lower in countries like Japan compared with the Western world. Western countries' LC n-3 PUFA intakes are up to 5 fold lower than Japanese intakes. Various professional bodies and government organisations recommend 500mg LC n-3 PUFA per day. The actual reported intake of LC n-3 PUFA from Australia and various other countries are compared to these recommended intakes. Not surprisingly, the actual intakes of LC n-3 PUFA in Western countries fall short of the recommended intakes. Consumption of fish and seafood is the easiest way to achieve the recommended intakes but increased consumption of foods enriched with LC n-3 PUFA will also contribute to achieving the recommended intakes. Most people are not consuming enough LC n-3 PUFA for optimal health.
Assuntos
Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Ácidos Graxos Ômega-3 , Alimentos Marinhos , Austrália , Humanos , Japão/epidemiologiaRESUMO
AIM: Physically active compared to inactive pre-menopausal women typically possess higher high-density lipoprotein (HDL) cholesterol and reduced plasma fibrinogen levels. The aim of this study was to compare resting blood lipid and fibrinogen levels of aerobically trained and untrained postmenopausal females. METHODS: Subjects were 13 aerobically trained (trained) and 26 untrained postmenopausal females (untrained) all on hormonal replacement therapy. Mean age of trained was 56 years (SD=3.6) and untrained was 58 years (SD=4.1). Testing involved blood sampling after an overnight fast. Plasma blood lipids were assessed through enzymatic methods, whereas plasma fibrinogen was measured through the Clauss method. RESULTS: Trained compared to untrained had significantly greater free fatty acid (51%, p<0.05) and apolipoprotein A levels (24%, p<0.05) and significantly lower fibrinogen (20%, p<0.05). Trained compared to untrained also possessed significantly lower total cholesterol/HDL cholesterol ratio (20%, p<0.05), total cholesterol/apolipoprotein A ratio (19%, p<0.05), apolipoprotein B/apolipoprotein A ratio (35%, p<0.05), and significantly higher HDL cholesterol (22%, p<0.05) although these differences were not significant after adjusting for body mass index (BMI). CONCLUSION: These results show that both a physically active lifestyle and a low BMI contribute to the improved lipid and fibrinogen levels of exercising postmenopausal women.
Assuntos
Ácidos Graxos não Esterificados/sangue , Fibrinogênio/análise , Lipoproteínas/sangue , Aptidão Física , Pós-Menopausa/sangue , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
To investigate a possible association of ABO blood group alleles with myocardial infarction, a case-control study comprising 177 patients (median age 57.0 years; range 32-72 years) and 89 controls was performed. The distributions of the ABO blood-genotype O1, O2, A1, A2 and B alleles were assessed by analysis of genomic DNA, using the sequence-specific primer-polymerase chain reaction (PCR-SSP) technique to investigate exons VI and VII on chromosome 9. The prevalence of the B allele was 2.5 times higher amongst patients with a history of myocardial infarction than amongst controls (16.3 vs. 6.7%; P = 0.034, Fisher's exact test). There was an association between patients carrying the B allele and myocardial infarction, with an odds ratio (OR) of 2.7 (95% confidence interval 1.1-6.8). The B allele remained an independent risk factor for myocardial infarction (P = 0.038) when classical risk factors were adjusted for by unconditional logistic regression. In conclusion, the ABO blood group B allele was found to be an independent risk factor for myocardial infarction.
Assuntos
Sistema ABO de Grupos Sanguíneos/genética , Alelos , Predisposição Genética para Doença , Infarto do Miocárdio/genética , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de RegressãoRESUMO
Aspirin treatment for primary prevention is safe and useful at an annual coronary event risk > or = 1.5%. Both aspirin and clopidogrel reduce the rate of cardiovascular events in patients with coronary disease. Clopidogrel in addition to aspirin further reduces cardiovascular events, but is associated with and increased bleeding risk. Recent studies in patients with myocardial infarction suggest that treatment with either coumadin or with coumadin and aspirin are both at least as effective than treatment with aspirin alone. Thromboembolism and bleeding during therapeutic anticoagulation are the major chronic risks for patients with native valvular heart disease and mechanical prosthetic valves. The recommendations for the prevention of thromboembolic events and bleeding complications are discussed and recommended intensity of antithrombotic therapy are outlined. Key points of the guidelines for managing patients with atrial fibrillation are summarised.
Assuntos
Anticoagulantes/uso terapêutico , Aspirina/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Fibrinolíticos/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Ticlopidina/uso terapêutico , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Doenças Cardiovasculares/tratamento farmacológico , Ensaios Clínicos como Assunto , Clopidogrel , Quimioterapia Combinada , Fibrinolíticos/administração & dosagem , Fibrinolíticos/efeitos adversos , Próteses Valvulares Cardíacas , Hemorragia/induzido quimicamente , Humanos , Infarto do Miocárdio/prevenção & controle , Placebos , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Guias de Prática Clínica como Assunto , Prevenção Primária , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Acidente Vascular Cerebral/prevenção & controle , Tromboembolia/induzido quimicamente , Ticlopidina/administração & dosagem , Ticlopidina/efeitos adversos , Ticlopidina/análogos & derivadosRESUMO
Our perception of the mechanisms underlying the acute complications of atherosclerosis has significantly changed in the last decade. Most coronary thromboses result from a rupture or a fissure in the protective fibrous cap of atherosclerotic plaque, but less common from a superficial erosion. The extent of thrombosis is a determinant of the clinical picture of acute coronary syndromes. Until now, we held a high grade stenosis responsible for the vast majority of acute coronary syndromes. However, current findings establish the relevance of qualitative aspects of plaques as important determinants of the vulnerability of plaques, i.e. the risk to cause acute complications. Among morphologic and functional features of plaques, inflammation has emerged as a leading pathophysiologic mechanism. In addition to local effect of inflammation at the level of the unstable plaque itself, systemic factors of the inflammatory response may alter the thrombogenicity of a vulnerable plaque. Knowledge of the role of inflammation helps us to understand the mechanisms by which therapeutic efforts can reduce clinical events. The clinical benefits of dietary modifications, pharmacotherapy with statins, and ACE inhibitors may be due in part to an anti-inflammatory action.
Assuntos
Proteínas de Fase Aguda/fisiologia , Doença da Artéria Coronariana/imunologia , Infarto do Miocárdio/imunologia , Animais , Apoptose/fisiologia , Doença da Artéria Coronariana/patologia , Trombose Coronária/imunologia , Trombose Coronária/patologia , Endotélio Vascular/imunologia , Endotélio Vascular/patologia , Humanos , Músculo Liso Vascular/imunologia , Músculo Liso Vascular/patologia , Infarto do Miocárdio/patologia , Fatores de RiscoRESUMO
BACKGROUND: Iron accumulation may contribute to coronary heart disease by catalysing free radical formation and promoting oxidation of low-density lipoprotein cholesterol. Epidemiological studies of iron status and coronary heart disease are conflicting. DESIGN: To test whether genetic haemochromatosis is associated with myocardial infarction, we determined the prevalence of three mutations in the HFE gene (Cys282Tyr, His63Asp and Ser65Cys) in a 2 : 1 case-control study including 177 patients who survived an acute myocardial infarction and 89 controls. Genotypes were determined by PCR amplification of genomic DNA followed by restriction enzyme digestion. We also studied the relationship between plasma ferritin and myocardial infarction. RESULTS: The carrier frequencies of these three mutations were not statistically different among patients and controls (Cys282Tyr: 1.4 vs. 10.1%; His63Asp: 26.5 vs. 31.5%; Ser65Cys: 2.8 vs. 1.1%). Mean ferritin levels were elevated among patients (176 +/- 155 microg L(-1)) compared with controls (131 +/- 106 microg L(-1), P = 0.015). Subjects with plasma ferritin concentrations of 300 microg L(-1) or more had a 2.9-fold (95% CI: 1.2-7.3, P = 0.02) unadjusted risk for a myocardial infarction compared with those with normal levels. In a univariate analysis, ferritin was significantly associated with myocardial infarction. Upon multiple regression analysis adjusting for smoking, hypertension, diabetes, body-mass index and total cholesterol, significance was no longer present. CONCLUSIONS: No direct association was found between genetic haemochromatosis and myocardial infarction among Swiss whites. Raised ferritin levels among patients suggest a role of increased iron stores in myocardial infarction, but iron overload was not an independent risk factor for Swiss coronary heart disease patients.
Assuntos
Ferritinas/sangue , Hemocromatose/epidemiologia , Hemocromatose/genética , Proteínas de Membrana , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/genética , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Antígenos HLA/genética , Hemocromatose/sangue , Proteína da Hemocromatose , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Mutação Puntual , Prevalência , Fatores de Risco , Suíça/epidemiologiaRESUMO
Macromolecular structures called kinetochores attach and move chromosomes within the spindle during chromosome segregation. Using electron microscopy, we identified a structure on the holocentric mitotic and meiotic chromosomes of Caenorhabditis elegans that resembles the mammalian kinetochore. This structure faces the poles on mitotic chromosomes but encircles meiotic chromosomes. Worm kinetochores require the evolutionarily conserved HIM-10 protein for their structure and function. HIM-10 localizes to the kinetochores and mediates attachment of chromosomes to the spindle. Depletion of HIM-10 disrupts kinetochore structure, causes a failure of bipolar spindle attachment, and results in chromosome nondisjunction. HIM-10 is related to the Nuf2 kinetochore proteins conserved from yeast to humans. Thus, the extended kinetochores characteristic of C. elegans holocentric chromosomes provide a guide to the structure, molecular architecture, and function of conventional kinetochores.
Assuntos
Centrômero/fisiologia , Proteínas de Helminto/metabolismo , Cinetocoros/fisiologia , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/fisiologia , Segregação de Cromossomos , Células Germinativas , Proteínas de Helminto/genética , Humanos , Masculino , Meiose , Mitose/fisiologiaRESUMO
UNLABELLED: The utility of bispectral index (BIS) monitoring to guide anesthetic administration has been demonstrated in adults. This prospective, randomized observer-blinded study was designed to evaluate the effect of BIS monitoring on anesthetic use and recovery characteristics in pediatric patients. After data collection in 38 historical controls, 202 patients age 0-18 yr were randomized into one of two groups: standard practice (SP) and BIS guided (BIS). Patients age 0-3 yr undergoing inguinal hernia repair (IH) and patients age 3-18 yr undergoing tonsillectomy and/or adenoidectomy (TA) were selected. All patients were anesthetized with sevoflurane in 60% N(2)O/O(2). Hernia patients also received a caudal epidural anesthetic before surgery. In the BIS group, anesthetic delivery was adjusted in an effort to achieve a target BIS of 45-60 during maintenance and 60-70 during the last 15 min of the procedure. BIS was recorded throughout surgery in all patients, but data were unavailable to the anesthesiologist in the SP group. In the TA patients, BIS monitoring was associated with a significant reduction in end-tidal sevoflurane concentration during maintenance (2.4 +/- 0.6%, SP and 1.8 +/- 0.4% BIS, mean +/- SD) and during the last 15 min of the procedure (2.1 +/- 0.7, SP and 1.6 +/- 0.6, BIS). There was a 25%-40% decrease in measured recovery times. In the patients 0-6 mo of age undergoing IH, sevoflurane concentrations during maintenance (2.0 +/- 0.4% SP, 0.9 +/- 0.8 BIS), during the last 15 min (1.6 +/- 0.4% SP, 0.6 +/- 0.6% BIS), and at the end of the procedure (1.1 +/- 0.6% SP, 0.3 +/- 0.3% BIS) were smaller in the BIS group. Emergence and recovery measures were unaffected by BIS titration. In the children 6 mo-3 yr of age, there were no significant differences between the SP and BIS groups in anesthetic use or recovery measures. IMPLICATIONS: Bispectral index monitoring in children results in less anesthetic use and faster recovery than standard practice.
Assuntos
Anestesia por Inalação , Anestésicos Inalatórios , Eletroencefalografia/efeitos dos fármacos , Éteres Metílicos , Monitorização Intraoperatória/métodos , Óxido Nitroso , Adenoidectomia , Adolescente , Fatores Etários , Anestésicos Inalatórios/administração & dosagem , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Herniorrafia , Humanos , Lactente , Recém-Nascido , Masculino , Éteres Metílicos/administração & dosagem , Óxido Nitroso/administração & dosagem , Estudos Prospectivos , Sevoflurano , TonsilectomiaRESUMO
The dosage compensation machinery of Caenorhabditis elegans is targeted specifically to the X chromosomes of hermaphrodites (XX) to reduce gene expression by half. Many of the trans-acting factors that direct the dosage compensation machinery to X have been identified, but none of the proposed cis-acting X chromosome-recognition elements needed to recruit dosage compensation components have been found. To study X chromosome recognition, we explored whether portions of an X chromosome attached to an autosome are competent to bind the C. elegans dosage compensation complex (DCC). To do so, we devised a three-dimensional in situ approach that allowed us to compare the volume, position, and number of chromosomal and subchromosomal bodies bound by the dosage compensation machinery in wild-type XX nuclei and XX nuclei carrying an X duplication. The dosage compensation complex was found to associate with a duplication of the right 30% of X, but the complex did not spread onto adjacent autosomal sequences. This result indicates that all the information required to specify X chromosome identity resides on the duplication and that the dosage compensation machinery can localize to a site distinct from the full-length hermaphrodite X chromosome. In contrast, smaller duplications of other regions of X appeared to not support localization of the DCC. In a separate effort to identify cis-acting X recognition elements, we used a computational approach to analyze genomic DNA sequences for the presence of short motifs that were abundant and overrepresented on X relative to autosomes. Fourteen families of X-enriched motifs were discovered and mapped onto the X chromosome.
Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans/genética , Cromossomos/genética , Transtornos do Desenvolvimento Sexual/genética , Mecanismo Genético de Compensação de Dose , Translocação Genética , Cromossomo X/genética , Animais , Caenorhabditis elegans/embriologia , Proteínas de Transporte/fisiologia , Proteínas de Ciclo Celular/fisiologia , Núcleo Celular/ultraestrutura , Proteínas Cromossômicas não Histona/fisiologia , Proteínas de Ligação a DNA/fisiologia , Desenvolvimento Embrionário , Duplicação Gênica , Regulação da Expressão Gênica , Proteínas de Helminto/fisiologia , Processamento de Imagem Assistida por Computador , Substâncias Macromoleculares , Microscopia Confocal , Proteínas Nucleares/fisiologiaRESUMO
OBJECTIVES: We sought to compare the inhibitory effects of the combination of two doses of aspirin plus clopidogrel with either drug alone on platelet aggregation and activation. BACKGROUND: Enhanced platelet inhibitory effects of clopidogrel by aspirin on platelet aggregation and activation are suggested by experimental studies but have not been shown in humans. METHODS: The effects of clopidogrel 75 mg or aspirin 100 (300) mg on platelet aggregation and activation by flow cytometry after stimulation with various agonists were determined in 30 patients with a past history of myocardial infarction. RESULTS: Clopidogrel alone or in combination with aspirin markedly inhibited adenosine diphosphate (ADP)-mediated platelet aggregation compared with monotherapy with aspirin (24.6 +/- 3.3% or 26.6 +/- 2.7% vs. 44.7 +/- 2.9%; p < 0.001). Combined treatment significantly inhibited collagen-induced aggregation compared with aspirin and clopidogrel (16.4 +/- 2.4%, 36.5 +/- 4.2% and 59.3 +/- 5.1%, respectively;, p < 0.001) and resulted in considerable inhibition of aggregation induced by thrombin receptor agonist peptide (TRAP, p < 0.03). Clopidogrel with or without aspirin significantly suppressed expression of platelet activation markers CD 62p, CD 63 and PAC-1 after stimulation with ADP or thrombin (p < 0.001). In addition, the combined treatment was more effective than either agent alone after activation with low dose thrombin (p < 0.05). Both doses of aspirin equally potentiated the platelet inhibitory effects of clopidogrel. CONCLUSIONS In this prospective clinical ex vivo platelet study, clopidogrel was more effective than aspirin in inhibiting ADP-mediated platelet aggregation and activation. Clopidogrel in combination with aspirin showed synergistic inhibitory effects after stimulation with collagen and thrombin compared with monotherapies. Thus, this dual antiplatelet treatment strategy deserves further evaluation in clinical trials for secondary prevention of acute myocardial infarction or unstable angina.
Assuntos
Aspirina/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Ticlopidina/análogos & derivados , Ticlopidina/uso terapêutico , Difosfato de Adenosina/farmacologia , Adulto , Idoso , Antígenos CD/metabolismo , Aspirina/administração & dosagem , Sangue/efeitos dos fármacos , Clopidogrel , Colágeno/farmacologia , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Fosfatase 2 de Especificidade Dupla , Humanos , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Selectina-P/metabolismo , Fragmentos de Peptídeos/farmacologia , Ativação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Glicoproteínas da Membrana de Plaquetas/metabolismo , Estudos Prospectivos , Proteína Fosfatase 2 , Proteínas Tirosina Fosfatases/metabolismo , Tetraspanina 30RESUMO
The nematode Caenorhabditis elegans counts its X chromosomes to determine sex and to activate the process of dosage compensation, which ensures that males (XO) and hermaphrodites (XX) express equal levels of most X-chromosome products. The number of X chromosomes is communicated by a set of X-linked genes called X-signal elements, which repress the master sex-determination switch gene xol-1 via two distinct, dose-dependent molecular mechanisms in XX embryos. X-chromosome gene dosage is compensated by a specialized protein complex that includes evolutionarily conserved components of mitotic and meiotic machinery. This complex assembles on both X chromosomes of hermaphrodites to repress transcription by half. The recruitment of chromosome segregation proteins to the new task of regulating X-chromosome-wide gene expression points to the evolutionary origin of nematode dosage compensation.
Assuntos
Caenorhabditis elegans/fisiologia , Mecanismo Genético de Compensação de Dose , Cromossomo X , Animais , Feminino , Regulação da Expressão Gênica , Masculino , Sexo , Processos de Determinação SexualRESUMO
Hantaviruses include serious human pathogens that are maintained in nature in persistently infected rodents and that can also persistently infect cultured mammalian cells, causing little or no cytopathology. The mechanisms of hantavirus persistence are only beginning to be explored. Recent data point to subtle changes in the viral genome that might result in the differential regulation of replication and lead to persistence.
Assuntos
Infecções por Hantavirus/veterinária , Orthohantavírus/fisiologia , Doenças dos Roedores/virologia , Animais , Reservatórios de Doenças , Genoma Viral , Vírus Hantaan/fisiologia , Orthohantavírus/genética , Infecções por Hantavirus/virologia , Humanos , Replicação ViralRESUMO
Two independent, long-term infections were analyzed to determine whether changes in viral replication could contribute to the establishment and/or maintenance of persistent Seoul virus infections. Infected cell cultures initially contained high levels of infectious virus and intracellular viral RNA that peaked between approximately 7 to 16 days postinfection and then gradually declined until day 26. After day 26, the viral titers and the levels of the small (S), medium (M), and large (L) viral RNAs varied cyclically until the end of the studies. The changes in the concentrations of the RNAs and titer were similar in pattern and appeared to result from changes in the regulation of replication. Neither internal deletions nor an accumulation of nucleotide changes were found in the RNAs. However, fine mapping and sequence analysis revealed short deletions in some of the RNAs in the conserved complementary terminal sequences believed to contain the signals for initiation of replication and transcription. Deletions at the 3' termini of S, M, and L virus-sense RNAs (vRNAs) accumulated during the acute phase of infection just before the time that the viral titer and the concentration of vRNAs and virus complementary-sense RNAs (cRNAs) began to decline. The absence of deletions at the 5' termini of the S, M, and L cRNAs suggests that the 3'-deleted vRNAs may not be replication competent. Thus, as the percentage of 3'-deleted vRNAs increase in the population, they could potentially compete with standard virus and downregulate viral replication. Deletions at the 3' L cRNA and 5' L vRNA termini were also observed, and the proportion of these deleted RNAs varied cyclically during the infections. We propose a model in which terminal nucleotide deletions arise by nuclease activity of the viral polymerase. In addition, we speculate that cleaved terminal fragments might be used as primers during replication, resulting in the repair of some of the deleted RNAs.