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BACKGROUND: In 2016, an influenza A(H7N2) virus outbreak occurred in cats in New York City's municipal animal shelters. One human infection was initially detected. METHODS: We conducted a serological survey using a novel approach to rule out cross-reactive antibodies to other seasonal influenza viruses to determine whether additional A(H7N2) human infections had occurred and to assess exposure risk. RESULTS: Of 121 shelter workers, one had serological evidence of A(H7N2) infection, corresponding to a seroprevalence of 0.8% (95% confidence interval, .02%-4.5%). Five persons exhibited low positive titers to A(H7N2) virus, indicating possible infection; however, we could not exclude cross-reactive antibody responses to seasonal influenza viruses. The remaining 115 persons were seronegative. The seropositive person reported multiple direct cat exposures without using personal protective equipment and mild illness with subjective fever, runny nose, and sore throat. CONCLUSIONS: We identified a second case of A(H7N2) infection from this outbreak, providing further evidence of cat-to-human transmission of A(H7N2) virus.
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Anticuerpos Antivirales/sangre , Brotes de Enfermedades/veterinaria , Subtipo H7N2 del Virus de la Influenza A/inmunología , Gripe Aviar/virología , Gripe Humana/virología , Infecciones por Orthomyxoviridae/veterinaria , Adulto , Anciano , Animales , Aves , Gatos , Reacciones Cruzadas , Femenino , Humanos , Subtipo H7N2 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/transmisión , Masculino , Persona de Mediana Edad , Ciudad de Nueva York/epidemiología , Infecciones por Orthomyxoviridae/epidemiología , Infecciones por Orthomyxoviridae/virología , Estudios Seroepidemiológicos , ZoonosisRESUMEN
To assess the association between vitamin C intake and cervical neoplasia (CN) risk. Databases including PubMed, Embase, and Springer link were retrieved up to June 10, 2014 with predefined strategy. The combined odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated for overall and subgroup analyses. The publication bias was assessed using Begg's test and Egger's test. Sensitivity analysis was also conducted. Twelve studies consisting of 1 prospective cohort study and 11 case-control studies were included. In overall analysis, vitamin C intake was significantly associated with the reduced risk of CN (OR = 0.58; 95% CI: 0.44 to 0.75; P < 0.001). Subgroup analysis stratified by vitamin C dose indicated all dose categories achieved a reduced CN risk. Furthermore, increased vitamin C intake by 50 mg/day was related to the reduced risk of CN (OR = 0.92; 95% CI: 0.89 to 0.94; P < 0.05). No publication bias was detected by Begg's test (P = 0.169) and no apparent fluctuation was observed in summary OR by sensitivity analysis. Vitamin C intake was inversely associated with the risk of CN and this association was dose-dependent. However, more randomized controlled trials are required for further validation.
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Ácido Ascórbico/administración & dosificación , Neoplasias del Cuello Uterino/prevención & control , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Sesgo de Publicación , Factores de RiesgoRESUMEN
OBJECTIVE: To explore the value of cervical liquid-based cytology test (LCT) and high-risk human papilloma virus for patients of high-grade squamous intraepithelial lesion (HSIL) excised with positive margins by loop electrosurgical excision procedure (LEEP). METHODS: A total of 404 HSIL patients with positive margins by LEEP and a follow-up of 12 months between June 2004 to April 2013 were recruited. The results of LCT, high-risk human papillomavirus (HR-HPV) DNA were analyzed retrospectively. According to the pathological diagnosis of re-operation, the results of LCT and HR-HPV DNA were analytically predicted for focal residue and recurrence. RESULTS: For patients with HSIL excised with positive margins by LEEP, the re-positive abnormality rate of LCT and/or HPV was 18.7% and the sustained positive rate of LCT and/or HPV 51.1%. The significance prediction of LCT and HR-HPV DNA examination for persistent and recurrent cervical dysplasia had a positive predictive value of 60%, a sensitivity of 100%, a positive likelihood ratio of 2.1, a negative likelihood ratio of 0.5 and an odds ratio of 4.5. CONCLUSION: For patients of HSIL excised with positive margins by loop electrosurgical excision procedure, LCT plus HR-HPV test may be effective after operation. And the positive results should be re-evaluated by colposcopy to provide rationales for re-operation.
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Infecciones por Papillomavirus , Lesiones Intraepiteliales Escamosas de Cuello Uterino , Colposcopía , Electrocirugia , Femenino , Humanos , Embarazo , Estudios Retrospectivos , Neoplasias del Cuello UterinoRESUMEN
The inflammasome is a vital part of the host's innate immunity activated by cellular infection or stress. Our previous research identified the bovine SP110c isoform (bSP110c) as a novel activator of the inflammasome that promoted the secretion of proinflammatory cytokines IL-1ß and IL-18 in macrophages infected with Listeria monocytogenes or stimulated with lipopolysaccharide (LPS). However, the exact molecular mechanism for inhibiting bSP110c-induced inflammasome activation requires further clarification. Here, the researchers identified bovine DDX3X (bDDX3X) as an NLRP3-associated protein and an inhibitor of the bSP110c-induced inflammasome in the human THP1 macrophage cell line. Immunoprecipitation showed that bDDX3X interacted with the bSP110c CARD domain via its helicase domain. The co-expression of bSP110c and bDDX3X in THP1 macrophages significantly prevented the bSP110c-induced activation of inflammasomes. In addition, both bDDX3X and bSP110c interacted with bovine NLRP3 (bNLRP3), and bDDX3X enhanced the interaction between bSP110c and bNLRP3. The expression of bDDX3X in nigericin-stimulated THP1 macrophages significantly suppressed NLRP3 inflammasome activation, ASC speck formation, and pyroptosis. These findings demonstrate that bDDX3X negatively regulates the bSP110c-mediated inflammatory response by restricting the activation of the NLRP3 inflammasome. This discovery unveils a novel regulatory mechanism involving bDDX3X and bSP110c in coordinating inflammasome activation and subsequent cell-fate decisions in LPS-treated macrophages and, in turn, constitutes a step forward toward the implementation of marker-assisted selection in breeding programs aimed at utilizing cattle's immune defenses.
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BACKGROUND: Some patients with cervical low-grade squamous intraepithelial lesions (LSIL) undergo invasive laser ablation or loop electrosurgical excision procedures. Photodynamic therapy (PDT) is a photosensitizer 5-aminolevulinic acid (5-ALA)-based minimally invasive technique that causes minimal normal tissue and cell damage. We investigated 5-ALA-mediated PDT efficacy for cervical LSIL complicated by human papillomavirus (HPV). METHODS: This prospective cohort study was conducted on patients with cervical LSIL, who were divided into treatment (20% 5-ALA PDT thrice every 7-14 days; n=216) and control (observation; n=220) groups. The treatment group underwent cervical cytology and HPV genotyping 3 months after treatment; both groups underwent cervical cytology, HPV genotyping, colposcopy biopsy, and histopathological examination 6 and 12 months post-treatment. RESULTS: The 3-, 6-, and 12-month follow-ups revealed gradually improved cervical cytology findings: no intraepithelial lesions or malignant tumor (NILM) rates (approximately 80%). The HPV clearance rate (baseline subtype) was approximately 68%: approximately 60% for HPV16/18 and 71% for non-HPV16/18 baseline subtypes. By months 6 and 12 after PDT, the LSIL regression rate of cervical histopathology increased (75.46%-82.08%). The 6- and 12-month follow-ups revealed significantly increased cervical LSIL regression rates in the treatment group. Compared with the control group, the number of HPV subtypes in the treatment group decreased significantly by 6 and 12 months. CONCLUSIONS: 5-ALA PDT effectively eliminated cervical LSIL and HPV, with sustained effects for up to 12 months post-treatment. Therefore, 5-ALA PDT is an effective and safe treatment for cervical LSIL with HPV that promotes cervical LSIL regression to normal cervical tissue.
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BACKGROUND: Few studies have focused on the immune response to more recent influenza vaccine formulations such as cell-cultured inactivated influenza vaccine (ccIIV4) or live-attenuated influenza vaccine (LAIV4) in older children and young adults, or differences in immunoglobulin response using newer antibody landscape technology. METHODS: Participants ages 4-21 were randomized to receive ccIIV4 (n = 112) or LAIV4 (n = 118). A novel high-throughput multiplex influenza antibody detection assay was used to provide detailed IgG, IgA, and IgM antibody isotypes, along with hemagglutination inhibition levels (HAI), measured pre- and 28 days post-vaccination. RESULTS: The HAI and immunoglobulin isotype response to ccIIV4 was greater than LAIV4, with significant increases in IgG but not IgA or IgM. The youngest participants had the highest LAIV4 response. Prior LAIV4 vaccination was associated with a higher response to current season ccIIV4. Cross-reactive A/Delaware/55/2019(H1N1)pdm09 antibodies were present pre-vaccination and increased in response to ccIIV4, but not LAIV4. Immunoglobulin assays strongly correlated with and confirmed the findings of HAI titers to measure immune response. CONCLUSIONS: Age and prior season vaccination may play a role in the immune response in children and young adults to ccIIV4 and LAIV4. While immunoglobulin isotypes provide high-level antigen-specific information, HAI titers alone can provide a meaningful representation of day 28 post-vaccination response. CLINICAL TRIALS NO: NCT03982069.
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Subtipo H1N1 del Virus de la Influenza A , Vacunas contra la Influenza , Gripe Humana , Adulto Joven , Humanos , Niño , Gripe Humana/prevención & control , Gripe Humana/tratamiento farmacológico , Anticuerpos Antivirales , Vacunas Atenuadas , Vacunas de Productos Inactivados , Pruebas de Inhibición de Hemaglutinación , Inmunoglobulina GRESUMEN
It is vital to develop general models that can be shared across subjects and sessions in the real-world deployment of electroencephalogram (EEG) emotion recognition systems. Many prior studies have exploited domain adaptation algorithms to alleviate the inter-subject and inter-session discrepancies of EEG distributions. However, these methods only aligned the global domain divergence, but overlooked the local domain divergence with respect to each emotion category. This degenerates the emotion-discriminating ability of the domain invariant features. In this paper, we argue that aligning the EEG data within the same emotion categories is important for generalizable and discriminative features. Hence, we propose the dynamic domain adaptation (DDA) algorithm where the global and local divergences are disposed by minimizing the global domain discrepancy and local subdomain discrepancy, respectively. To tackle the absence of emotion labels in the target domain, we introduce a dynamic training strategy where the model focuses on optimizing the global domain discrepancy in the early training steps, and then gradually switches to the local subdomain discrepancy. The DDA algorithm is formally implemented as an unsupervised version and a semi-supervised version for different experimental settings. Based on the coarse-to-fine alignment, our model achieves the average peak accuracy of 91.08%, 92.89% on SEED, and 81.58%, 80.82% on SEED-IV in the cross-subject and cross-session scenarios, respectively.
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Electroencefalografía , Emociones , Humanos , Electroencefalografía/métodos , AlgoritmosRESUMEN
Although some adults infected with influenza 2009 A(H1N1)pdm09 viruses mounted high hemagglutination inhibition (HAI) antibody response, they still suffered from severe disease, or even death. Here, we analyzed antibody profiles in patients (n = 31, 17-65 years) admitted to intensive care units (ICUs) with lung failure and invasive mechanical ventilation use due to infection with A(H1N1)pdm09 viruses during 2009-2011. We performed a comprehensive analysis of the quality and quantity of antibody responses using HAI, virus neutralization, biolayer interferometry, enzyme-linked-lectin and enzyme-linked immunosorbent assays. At time of the ICU admission, 45% (14/31) of the patients had HAI antibody titers ≥ 80 in the first serum (S1), most (13/14) exhibited narrowly-focused HAI and/or anti-HA-head binding antibodies targeting single epitopes in or around the receptor binding site. In contrast, 42% (13/31) of the patients with HAI titers ≤ 10 in S1 had non-neutralizing anti-HA-stem antibodies against A(H1N1)pdm09 viruses. Only 19% (6/31) of the patients showed HA-specific IgG1-dominant antibody responses. Three of 5 fatal patients possessed highly focused cross-type HAI antibodies targeting the (K130 + Q223)-epitopes with extremely low avidity. Our findings suggest that narrowly-focused low-quality antibody responses targeting specific HA-epitopes may have contributed to severe infection of the lower respiratory tract.
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Deficiencia de IgA , Subtipo H1N1 del Virus de la Influenza A , Vacunas contra la Influenza , Gripe Humana , Adulto , Anticuerpos Antivirales , Formación de Anticuerpos , Enfermedad Crítica , Epítopos , Glicoproteínas Hemaglutininas del Virus de la Influenza , HumanosRESUMEN
Viral vectors based on influenza virus, rabies virus (RV), and vaccinia virus (VV) were used to express large polypeptide segments derived from the Bacillus anthracis protective antigen (PA). For the infectious influenza virus vector and recombinant VV constructs, the receptor binding domain (RBD or domain 4) or the lethal and edema factor binding domain (LEF or domain 1') were engineered into functional chimeric hemagglutinin (HA) glycoproteins. In the case of the RV vector, the viral glycoprotein (G) was used as a carrier for RBD in an inactivated form of the vector. These constructs were examined by using multiple homologous and heterologous prime/boost immunization regimens in order to optimize the induction of alpha-PA antibody responses. Several immunization combinations were shown to induce high titers of antibody recognizing the anthrax RBD and LEF domains, as well as the full-length PA protein in mice. The heterologous prime/boost immunization regimens that involved an initial intranasal administration of a live influenza virus vector, followed by an intramuscular boost with either the killed RV vector or the VV vector, were particularly effective, inducing antigen-specific antibodies at levels severalfold higher than homologous or alternative heterologous protocols. Furthermore, sera from several groups of the immunized mice demonstrated neutralization activity in an in vitro anthrax toxin neutralization assay. In some cases, such toxin-neutralizing activity was notably high, indicating that the mechanisms by which immunity is primed by live influenza virus vectors may have beneficial properties.
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Vacunas contra el Carbunco/inmunología , Anticuerpos Antibacterianos/inmunología , Anticuerpos Neutralizantes/inmunología , Antígenos Bacterianos/inmunología , Antitoxinas/inmunología , Toxinas Bacterianas/inmunología , Vectores Genéticos , Orthomyxoviridae/genética , Animales , Vacunas contra el Carbunco/genética , Femenino , Inmunización Secundaria/métodos , Ratones , Ratones Endogámicos BALB C , Virus de la Rabia/genética , Vacunación/métodos , Virus Vaccinia/genéticaRESUMEN
Emotion recognition based on electroencephalography (EEG) plays a pivotal role in the field of affective computing, and graph convolutional neural network (GCN) has been proved to be an effective method and made considerable progress. Since the adjacency matrix that can describe the electrode relationships is critical in GCN, it becomes necessary to explore effective electrode relationships for GCN. However, the setting of the adjacency matrix and the corresponding value is empirical and subjective in emotion recognition, and whether it matches the target task remains to be discussed. To solve the problem, we proposed a graph convolutional network with learnable electrode relations (LR-GCN), which learns the adjacency matrix automatically in a goal-driven manner, including using self-attention to forward update the Laplacian matrix and using gradient propagation to backward update the adjacency matrix. Compared with previous works that use simple electrode relationships or only the feature information, LR-GCN achieved higher emotion recognition ability by extracting more reasonable electrode relationships during the training progress. We conducted a subject-dependent experiment on the SEED database and achieved recognition accuracy of 94.72% on the DE feature and 85.24% on the PSD feature. After visualizing the optimized Laplacian matrix, we found that the brain connections related to vision, hearing, and emotion have been enhanced.
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Electroencefalografía , Redes Neurales de la Computación , Encéfalo , Electrodos , EmocionesRESUMEN
Electroencephalogram (EEG)-based emotion recognition has made great progress in recent years. The current pipelines collect EEG training data in a long-time calibration session for each new subject, which is time consuming and user unfriendly. To reduce the time required for the calibration session, there have been many studies using domain adaptation (DA) approaches to transfer knowledge from existing subjects (source domain) to the new subject (target domain) for reducing the dependence on the calibration session. Existing DA methods usually require substantial unlabeled EEG data of the new subject. However, the real scenario is that there are a small number of labeled samples in the calibration session of the target. Motivated by this, we introduce a novel domain adaptation architecture based on adversarial training to learn domain-invariant feature representations across subjects. To improve the performance when there are few labeled EEG data in the calibration session, we add a soft label loss to the architecture, which can ensure that the inter-class relationships learned from the source domain are transferred to target domain. We evaluate the method on the SEED dataset, and the experimental results show that our method uses only 15 examples per trial in the calibration session to achieve an average accuracy of 87.28%, indicating the effectiveness of our framework.
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Algoritmos , Electroencefalografía , Adaptación Fisiológica , Calibración , Emociones , HumanosRESUMEN
As an important element in the human-machine interaction, the electroencephalogram (EEG)-based emotion recognition has achieved significant progress. However, one obstacle to practicality lies in the variability between subjects and sessions. Although several studies have adopted domain adaptation (DA) approaches to tackle this problem, most of them treat multiple data from different subjects and different sessions together as a single source for transfer. Since different EEG data have different marginal distributions, these approaches fail to satisfy the assumption of DA that the source has a certain marginal distribution. We therefore propose the multi-source EEG-based emotion recognition network (MEERNet), which takes both domain-invariant and domain-specific features into consideration. Firstly we assume that different EEG data share the same low-level features, and then we construct multiple branches corresponding to multiple sources to extract domain-specific features, and then DA is conducted between the target and each source. Finally, the inference is made by multiple branches. We evaluate our method on SEED and SEED-IV for recognizing three and four emotions, respectively. Experimental results show that the MEERNet outperforms the single-source methods in cross-session and cross-subject transfer scenarios with an accuracy of 86.7% and 67.1% on average, respectively.
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Electroencefalografía , Emociones , Generalización Psicológica , HumanosRESUMEN
As an essential element for the diagnosis and rehabilitation of psychiatric disorders, the electroencephalogram (EEG) based emotion recognition has achieved significant progress due to its high precision and reliability. However, one obstacle to practicality lies in the variability between subjects and sessions. Although several studies have adopted domain adaptation (DA) approaches to tackle this problem, most of them treat multiple EEG data from different subjects and sessions together as a single source domain for transfer, which either fails to satisfy the assumption of domain adaptation that the source has a certain marginal distribution, or increases the difficulty of adaptation. We therefore propose the multi-source marginal distribution adaptation (MS-MDA) for EEG emotion recognition, which takes both domain-invariant and domain-specific features into consideration. First, we assume that different EEG data share the same low-level features, then we construct independent branches for multiple EEG data source domains to adopt one-to-one domain adaptation and extract domain-specific features. Finally, the inference is made by multiple branches. We evaluate our method on SEED and SEED-IV for recognizing three and four emotions, respectively. Experimental results show that the MS-MDA outperforms the comparison methods and state-of-the-art models in cross-session and cross-subject transfer scenarios in our settings. Codes at https://github.com/VoiceBeer/MS-MDA.
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To better understand the antibody landscape changes following influenza virus natural infection and vaccination, we developed a high-throughput multiplex influenza antibody detection assay (MIADA) containing 42 recombinant hemagglutinins (rHAs) (ectodomain and/or globular head domain) from pre-2009 A(H1N1), A(H1N1)pdm09, A(H2N2), A(H3N2), A(H5N1), A(H7N7), A(H7N9), A(H7N2), A(H9N2), A(H13N9), and influenza B viruses. Panels of ferret antisera, 227 paired human sera from vaccinees (children and adults) in 5 influenza seasons (2010 to 2018), and 17 paired human sera collected from real-time reverse transcription-PCR (rRT-PCR)-confirmed influenza A(H1N1)pdm09, influenza A(H3N2), or influenza B virus-infected adults were analyzed by the MIADA. Ferret antisera demonstrated clear strain-specific antibody responses to exposed subtype HA. Adults (19 to 49 years old) had broader antibody landscapes than young children (<3 years old) and older children (9 to 17 years old) both at baseline and post-vaccination. Influenza vaccination and infection induced the strongest antibody responses specific to HA(s) of exposed strain/subtype viruses and closely related strains; they also induced cross-reactive antibodies to an unexposed influenza virus subtype(s), including novel viruses. Subsequent serum adsorption confirmed that the cross-reactive antibodies against novel subtype HAs were mainly induced by exposures to A(H1N1)/A(H3N2) influenza A viruses. In contrast, adults infected by influenza B viruses mounted antibody responses mostly specific to two influenza B virus lineage HAs. Median fluorescence intensities (MFIs) and seroconversion in MIADA had good correlations with the titers and seroconversion measured by hemagglutination inhibition and microneutralization assays. Our study demonstrated that antibody landscape analysis by the MIADA can be used for influenza vaccine evaluations and characterization of influenza virus infections.IMPORTANCE Repeated influenza vaccination and natural infections generate complex immune profiles in humans that require antibody landscape analysis to assess immunity and evaluate vaccines. However, antibody landscape analyses are difficult to perform using traditional assays. Here, we developed a high-throughput, serum-sparing, multiplex influenza antibody detection assay (MIADA) and analyzed the antibody landscapes following influenza vaccination and infection. We showed that adults had broader antibody landscapes than children. Influenza vaccination and infection not only induced the strongest antibody responses to the hemagglutinins of the viruses of exposure, but also induced cross-reactive antibodies to novel influenza viruses that can be removed by serum adsorption. There is a good correlation between the median fluorescence intensity (MFI) measured by MIADA and hemagglutination inhibition/microneutralization titers. Antibody landscape analysis by the MIADA can be used in influenza vaccine evaluations, including the development of universal influenza vaccines and the characterization of influenza virus infections.
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Anticuerpos Antivirales/sangre , Vacunas contra la Influenza/inmunología , Orthomyxoviridae/inmunología , Vacunación , Adolescente , Adulto , Animales , Niño , Preescolar , Reacciones Cruzadas , Hurones , Ensayos Analíticos de Alto Rendimiento , Humanos , Lactante , Recién Nacido , Persona de Mediana Edad , Adulto JovenRESUMEN
To determine whether regular cervical dilatation is effective for preventing cervical stenosis, and to identify the associated risk factors, in postmenopausal women after LEEP. This was a prospective randomized clinical trial in postmenopausal women who underwent LEEP at our hospital between August 2018 and May 2019. Patients who met the study criteria were randomly allocated to three groups: control group (without any intervention), intervention group A (underwent cervical dilatation at the 3rd, 5th, and 8th week after LEEP) and intervention group B (underwent cervical dilatation at the 4th, 8th, and 12th week after LEEP). A colposcopic follow-up examination was conducted at 6 months after LEEP to determine the incidence of cervical stenosis. A total of 404 postmenopausal women were found to be finally eligible for the study. The rate of cervical stenosis in the control group was significantly higher than that in the intervention group, and the rate in group A was significantly lower than that in group B. We found regular dilatation after LEEP in postmenopausal women can prevent cervical stenosis. Further, the 3rd, 5th, and 8th weeks after LEEP are optimal time points. Finally, LEEP frequency and resection depth are significant risk factors and can be used to screen postmenopausal women at risk for cervical stenosis after LEEP.
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Constricción Patológica/prevención & control , Electrocirugia/efectos adversos , Posmenopausia , Neoplasias del Cuello Uterino/cirugía , Estudios de Casos y Controles , China/epidemiología , Constricción Patológica/epidemiología , Constricción Patológica/etiología , Constricción Patológica/patología , Femenino , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Factores de RiesgoRESUMEN
BACKGROUND: The development of serologic assays that can rapidly assess human exposure to novel influenza viruses remains a public health need. Previously, we developed an 11-plex magnetic fluorescence microsphere immunoassay (MAGPIX) by using globular head domain recombinant hemagglutinins (rHAs) with serum adsorption using two ectodomain rHAs. METHODS: We compared sera collected from two cohorts with novel influenza exposures: animal shelter staff during an A(H7N2) outbreak in New York City in 2016-2017 (n = 119 single sera) and poultry workers from a live bird market in Bangladesh in 2012-2014 (n = 29 pairs). Sera were analyzed by microneutralization (MN) assay and a 20-plex MAGPIX assay with rHAs from 19 influenza strains (11 subtypes) combined with serum adsorption using 8 rHAs from A(H1N1) and A(H3N2) viruses. Antibody responses were analyzed to determine the novel influenza virus exposure. RESULTS: Among persons with novel influenza virus exposures, the median fluorescence intensity (MFI) against the novel rHA from exposed influenza virus had the highest correlation with MN titers to the same viruses and could be confirmed by removal of cross-reactivity from seasonal H1/H3 rHAs following serum adsorption. Interestingly, in persons with exposures to novel influenza viruses, age and MFIs against exposed novel HA were negatively correlated, whereas in persons without exposure to novel influenza viruses, age and MFI against novel HAs were positively correlated. CONCLUSIONS: This 20-plex high-throughput assay with serum adsorption will be a useful tool to detect novel influenza virus infections during influenza outbreak investigations and surveillance, especially when well-paired serum samples are not available.
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Anticuerpos Antivirales/sangre , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Virus de la Influenza A/inmunología , Pruebas Serológicas/métodos , Adsorción , Animales , Bangladesh , Estudios de Cohortes , Glicoproteínas Hemaglutininas del Virus de la Influenza/sangre , Humanos , Subtipo H1N1 del Virus de la Influenza A/inmunología , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Subtipo H3N2 del Virus de la Influenza A/inmunología , Subtipo H3N2 del Virus de la Influenza A/aislamiento & purificación , Subtipo H7N2 del Virus de la Influenza A/inmunología , Subtipo H7N2 del Virus de la Influenza A/aislamiento & purificación , Virus de la Influenza A/aislamiento & purificación , Gripe Humana/virología , Ciudad de Nueva York , Suero/virologíaRESUMEN
During membrane fusion, the influenza A virus hemagglutinin (HA) adopts an extended helical structure that contains the viral transmembrane and fusion peptide domains at the same end of the molecule. The peptide segments that link the end of this rod-like structure to the membrane-associating domains are approximately 10 amino acids in each case, and their structure at the pH of fusion is currently unknown. Here, we examine mutant HAs and influenza viruses containing such HAs to determine whether these peptide linkers are subject to specific length requirements for the proper folding of native HA and for membrane fusion function. Using pairwise deletions and insertions, we show that the region flanking the fusion peptide appears to be important for the folding of the native HA structure but that mutant proteins with small insertions can be expressed on the cell surface and are functional for membrane fusion. HA mutants with deletions of up to 10 residues and insertions of as many as 12 amino acids were generated for the peptide linker to the viral transmembrane domain, and all folded properly and were expressed on the cell surface. For these mutants, it was possible to designate length restrictions for efficient membrane fusion, as functional activity was observed only for mutants containing linkers with insertions or deletions of eight residues or less. The linker peptide mutants are discussed with respect to requirements for the folding of native HAs and length restrictions for membrane fusion activity.
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Membrana Celular/metabolismo , Glicoproteínas Hemaglutininas del Virus de la Influenza/metabolismo , Péptidos/metabolismo , Estructura Terciaria de Proteína , Proteínas Virales de Fusión/metabolismo , Animales , Línea Celular , ADN Complementario/genética , Perros , Fluoresceínas , Células HeLa , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Humanos , Mutación/genética , Pliegue de ProteínaRESUMEN
The replicative properties of influenza virus hemagglutinin (HA) mutants with altered receptor binding characteristics were analyzed following intranasal inoculation of mice. Among the mutants examined was a virus containing a Y98F substitution at a conserved position in the receptor binding site that leads to a 20-fold reduction in binding. This mutant can replicate as well as wild-type (WT) virus in MDCK cells and in embryonated chicken eggs but is highly attenuated in mice, exhibiting titers in lungs more than 1,000-fold lower than those of the WT. The capacity of the Y98F mutant to induce antibody responses and the structural locations of HA reversion mutations are examined.
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Hemaglutininas Virales/genética , Hemaglutininas Virales/metabolismo , Virus de la Influenza A/genética , Virus de la Influenza A/patogenicidad , Mutación Missense , Proteínas Virales/genética , Proteínas Virales/metabolismo , Sustitución de Aminoácidos/genética , Animales , Anticuerpos Antivirales/sangre , Sitios de Unión , Peso Corporal , Línea Celular , Embrión de Pollo , Perros , Pruebas de Inhibición de Hemaglutinación , Virus de la Influenza A/crecimiento & desarrollo , Virus de la Influenza A/inmunología , Pulmón/virología , Ratones , Ratones Endogámicos BALB C , Modelos Moleculares , Infecciones por Orthomyxoviridae/prevención & control , Infecciones por Orthomyxoviridae/virología , Estructura Terciaria de Proteína , Virulencia , Replicación Viral/fisiologíaRESUMEN
To study deficiencies in knowledge of the general public health-care professionals in community health service centers regarding the prevention of cervical intraepithelial neoplasia and cervical cancer. In addition, this study examined the key content of training required for primary health-care personnel to prevent cervical precancerous lesion and cervical cancer.A questionnaire was distributed among 172 medical staff personnel (the ratio of general practitioners and nurses was 1:1 in five community health service centers in Shanghai, China. This questionnaire assessed four knowledge areas of cervical cancer prevention using 10 single-choice questions.Out the 172 questionnaires distributed, 105 (61.05%) were completed correctly. No statistically significant difference in the percentage of complete correct answers among the five community health service centers was seen (Pâ=â.06). Additionally, there was no significant difference in the percentage of correct answers among the three age groups surveyed: age ≤35 years, 36-45 years, and ≥46 years (Pâ=â.12). We did find a statistically significant difference in the percentage of correct answers between general practitioners and nurses (Pâ=â.01) and between staff with master's degrees, bachelor's degrees, and associate's degrees (Pâ=â.03).General practitioners and nurses in community health service centers in Shanghai require additional education on the secondary prevention of cervical intraepithelial neoplasia and cervical cancer. The health knowledge related to human papillomavirus also needs to improve. Nurses and medical staff with lower degrees have insufficient awareness of the prevention of precancerous lesions of the cervix and cervical cancer; these two groups should be prioritized for additional training.