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1.
J Med Virol ; 96(6): e29736, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38864349

RESUMEN

Although a range of blood traits have been reported to be associated with influenza A(H1N1)pdm09 (H1N1pdm09) disease severity, their underlying causal relationships and biological mechanisms have remained unclear. This study aimed to investigate the causal relationship between blood traits and H1N1pdm09 using a two-sample Mendelian randomization analysis. Based on the data from our in-house genome-wide association study (GWAS) on H1N1pdm09 disease severity (Ncase [severe] = 70, Ncontrol [mild] = 95) and GWAS summaries of 44 blood traits from Biobank Japan (N = 12 303-143 658), we identified the potential causal effect of blood traits on severe H1N1pdm09. The inverse variance weighted method analysis revealed significant causal effects of lower aspartate aminotransferase (AST, ß = -3.212, p = 0.019), low-density-lipoprotein cholesterol (LDL-C, ß = -1.372, p = 0.045), and basophil counts (Baso, ß = -1.638, p = 0.047) on severe H1N1pdm09 disease. Additionally, polygenic risk score analysis further confirmed genetic overlap between these blood traits and severe H1N1pdm09 disease. This study provided evidence linking the lower level of AST, LDL-C, and lower count of Baso with severe H1N1pdm09 disease, potentially identifying new therapeutic targets for patients with severe influenza.


Asunto(s)
Estudio de Asociación del Genoma Completo , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana , Análisis de la Aleatorización Mendeliana , Humanos , Gripe Humana/virología , Gripe Humana/genética , Gripe Humana/epidemiología , Subtipo H1N1 del Virus de la Influenza A/genética , Japón/epidemiología , Predisposición Genética a la Enfermedad , Índice de Severidad de la Enfermedad , Polimorfismo de Nucleótido Simple , Aspartato Aminotransferasas/sangre , LDL-Colesterol/sangre , Asia Oriental/epidemiología , Pueblo Asiatico/genética , Pueblos del Este de Asia
2.
Microorganisms ; 12(6)2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38930552

RESUMEN

Numerous studies have reported a correlation between gut microbiota and influenza A virus (IAV) infection and disease severity. However, the causal relationship between these factors remains inadequately explored. This investigation aimed to assess the influence of gut microbiota on susceptibility to human infection with H7N9 avian IAV and the severity of influenza A (H1N1)pdm09 infection. A two-sample Mendelian randomization analysis was conducted, integrating our in-house genome-wide association study (GWAS) on H7N9 susceptibility and H1N1pdm09 severity with a metagenomics GWAS dataset from a Chinese population. Twelve and fifteen gut microbiotas were causally associated with H7N9 susceptibility or H1N1pdm09 severity, separately. Notably, Clostridium hylemonae and Faecalibacterium prausnitzii were negative associated with H7N9 susceptibility and H1N1pdm09 severity, respectively. Moreover, Streptococcus peroris and Streptococcus sanguinis were associated with H7N9 susceptibility, while Streptococcus parasanguini and Streptococcus suis were correlated with H1N1pdm09 severity. These results provide novel insights into the interplay between gut microbiota and IAV pathogenesis as well as new clues for mechanism research regarding therapeutic interventions or IAV infections. Future studies should concentrate on clarifying the regulatory mechanisms of gut microbiota and developing efficacious approaches to reduce the incidence of IAV infections, which could improve strategy for preventing and treating IAV infection worldwide.

3.
Sensors (Basel) ; 24(12)2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38931628

RESUMEN

The Taiji program is dedicated to the detection of middle and low-frequency gravitational waves, targeting the 0.1 mHz to 1 Hz frequency band. The project requires an acceleration residual sensitivity of 3 × 10-15 ms-2/Hz1/2, which necessitates a capacitance sensing resolution of 1 aF/Hz1/2 for the capacitive sensing system within the specified frequency range. The noise level of the resonant bridge significantly influences the resolution. Addressing the challenges in enhancing transformer performance parameters in existing resonant capacitance bridges and the constraints on improving the characteristics of resonant capacitance bridges, this study introduces a novel approach to reduce bridge thermal noise without optimizing existing parameters. The simulation results demonstrate that this scheme can reduce the noise to 0.7 times the original level and further reduce bridge thermal noise when other parameters affecting noise are optimized. This not only mitigates the demands for other performance parameters but also increases the range of maximum acceptable resonant frequency deviations and reduces its sensitivity to such variations. Experimental validation confirms that the proposed scheme effectively reduces noise by 0.7 times and improves the resolution of capacitance sensing to 0.6 aF/Hz1/2, thereby advancing the Taiji program gravitational wave detection capabilities.

4.
Sensors (Basel) ; 24(3)2024 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-38339522

RESUMEN

An inertial sensor is a crucial payload in China's Taiji program for space gravitational wave detection. The performance of the capacitive displacement sensing circuit in the low-frequency band (0.1 mHz to 1 Hz) is extremely important because it directly determines the sensitivity of the space gravitational wave detection missions. Therefore, significant, yet challenging, tasks include decreasing the low-frequency noise in capacitive displacement sensing circuits and improving the capacitive sensing resolution. This study analyzes the noise characteristics of the pre-amplifier circuit within the capacitive sensing circuit, achieves precise tuning of the transformer bridge, and examines how transformer parameters affect noise. In addition, this study introduces a method using a discrete JFET to reduce the operational amplifier current noise and analyzes how feedback resistance and capacitance in TIA circuits affect the overall circuit noise. The proportional relationship between different transformer noises and TIA noise before and after optimization was analyzed and experimentally verified. Finally, an optimized TIA circuit and a superior transformer were utilized to achieve an increase in the capacitive sensing resolution from 1.095 aF/rtHz @ 10 mHz to 0.84 aF/rtHz @ 10 mHz, while improving the performance by 23%. These findings provide valuable insights into further decreasing circuit noise and increasing the capacitive sensing resolution.

5.
Am J Hum Genet ; 111(1): 181-199, 2024 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-38181733

RESUMEN

Human humoral immune responses to SARS-CoV-2 vaccines exhibit substantial inter-individual variability and have been linked to vaccine efficacy. To elucidate the underlying mechanism behind this variability, we conducted a genome-wide association study (GWAS) on the anti-spike IgG serostatus of UK Biobank participants who were previously uninfected by SARS-CoV-2 and had received either the first dose (n = 54,066) or the second dose (n = 46,232) of COVID-19 vaccines. Our analysis revealed significant genome-wide associations between the IgG antibody serostatus following the initial vaccine and human leukocyte antigen (HLA) class II alleles. Specifically, the HLA-DRB1∗13:02 allele (MAF = 4.0%, OR = 0.75, p = 2.34e-16) demonstrated the most statistically significant protective effect against IgG seronegativity. This protective effect was driven by an alteration from arginine (Arg) to glutamic acid (Glu) at position 71 on HLA-DRß1 (p = 1.88e-25), leading to a change in the electrostatic potential of pocket 4 of the peptide binding groove. Notably, the impact of HLA alleles on IgG responses was cell type specific, and we observed a shared genetic predisposition between IgG status and susceptibility/severity of COVID-19. These results were replicated within independent cohorts where IgG serostatus was assayed by two different antibody serology tests. Our findings provide insights into the biological mechanism underlying individual variation in responses to COVID-19 vaccines and highlight the need to consider the influence of constitutive genetics when designing vaccination strategies for optimizing protection and control of infectious disease across diverse populations.


Asunto(s)
COVID-19 , Inmunoglobulina G , Humanos , Formación de Anticuerpos/genética , Vacunas contra la COVID-19 , Estudio de Asociación del Genoma Completo , COVID-19/genética , COVID-19/prevención & control , SARS-CoV-2 , Vacunación
6.
Sensors (Basel) ; 23(22)2023 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-38005532

RESUMEN

In the space gravitational wave detection mission, inertial sensors play the role of providing an inertial reference for the laser interferometric measurement system. Among them, the capacitance sensor serves as the core key technology of the inertial sensor, used to measure the relative position of the test mass (TM) in the electrode cage. The capacitance sensor utilizes synchronous demodulation technology to extract signals from the AC induction signal. When the phase of the demodulation switch signal is aligned, the synchronous demodulator can most effectively filter out noise, thus directly influencing the performance of the capacitance sensor. However, since the TM is in a suspended state, the information read by the capacitance sensor is dynamic, which increases the difficulty of demodulation phase alignment. In light of this, a method is proposed for achieving the phase alignment of the demodulation switch signal in a dynamic environment. This is accomplished by adjusting the phase of the demodulation switch signal, and subsequently computing the phase difference between the AC induction signal and the demodulation switch signal. At the same time, a measurement and evaluation method for phase deviation is also proposed. Ultimately, an automatic phase alignment system for the demodulation switch signal in dynamic environments is successfully implemented on an FPGA platform, and tests are conducted on a hexapod PI console platform to simulate dynamic environments. The experimental results demonstrate that the system accurately achieves phase alignment in the static environment, with a phase deviation of 0.1394 rad. In the simulated dynamic environment, the phase deviation is 0.1395 rad.

7.
J Med Virol ; 95(11): e29266, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-38009617

RESUMEN

Avian influenza A viruses (IAVs) that cross the species barrier to infect humans have the potential to initiate a new pandemic. However, the host factors influencing avian IAV infection remain poorly understood. To address this knowledge gap, we conducted a two-sample Mendelian randomization (MR) analysis by integrating our in-house genome-wide association study (GWAS) of avian IAV H7N9 susceptibility (with 217 cases and 116 controls) with the largest GWAS of serum IgA levels to date (sample size 41 263). Using the inverse-variance weighted (IVW) method, we discovered that genetically decreased serum IgA levels were associated with an increased risk of H7N9 infection (ß = -2.528, 95% confidence interval [CI]: -4.572 to -0.484; p = 0.015). Consistent results were obtained from three other MR methods, including robust IVW estimation (ß = -2.506, 95% CI: -4.109 to -0.902; p = 0.002), generalized summary-data-based MR (GSMR) (ß = -2.238, 95% CI: -4.106 to -0.602; p = 0.019), and MR-pleiotropy residual sum and outlier (MR-PRESSO) (ß = -2.528, 95% CI: -4.396 to -0.892; p = 0.026). In conclusion, our analysis provided compelling evidence support a causal relationship between genetically predicted serum IgA levels and avian IAV H7N9 susceptibility.


Asunto(s)
Subtipo H7N9 del Virus de la Influenza A , Animales , Humanos , Subtipo H7N9 del Virus de la Influenza A/genética , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Bases de Datos Factuales , Inmunoglobulina A
8.
J Med Virol ; 95(7): e28893, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37394796

RESUMEN

There has been a substantial rise in coronavirus disease 2019 (COVID-19) cases after adjusting the dynamic zero-COVID policy in China. We conducted a survey to investigate the self-perceived symptom profile and its association with vaccination status during this outbreak. There were 552 individuals in this survey. The infected individuals displayed various symptoms associated with different factors. The three most common symptoms were fatigue (92.21%), phlegm (91.49%), and cough (89.31%). Two typical clusters of COVID-19 symptoms were identified through hierarchical clustering: one was the symptoms with a high probability of co-occurrence that primarily involved the upper respiratory tract, and the other was the symptoms with a high prevalence of severe cases that affected multiple systems. Symptoms exhibited distinct across regions. Hebei Province reported the most severe respiratory symptoms, and Chongqing City reported the worst neurological and digestive symptoms. Cough and fatigue occurred together in most regions. Nevertheless, the cough severity of Zhejiang, Liaoning, and Yunnan provinces was lower than in other areas (t-test p < 0.001). Regression analysis suggested a potential protective effect of recent vaccination on some symptoms. Compared with people who had been vaccinated within half a year, those for more than 1 year had a higher risk of developing phlegm, cough, vertigo, and nausea (all p < 0.05). Our study illustrated the characteristics and symptom profiles of COVID-19 during this wave and provided data supporting its relationship with multiple factors. These findings offered new insights into the recent COVID-19 pandemic in China.


Asunto(s)
COVID-19 , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , SARS-CoV-2 , Pandemias , Tos/epidemiología , China/epidemiología
9.
Plant Physiol Biochem ; 201: 107827, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37329689

RESUMEN

Woody bamboos are important resource of industrial fibres. Auxin signaling plays a key role in multiple plant developmental processes, as yet the role of auxin/indole acetic acid (Aux/IAA) in culm development of woody bamboos has not been previously characterized. Dendrocalamus sinicus Chia et J. L. Sun is the largest woody bamboo documented in the world. Here, we identified two alleles of DsIAA21 gene (sIAA21 and bIAA21) from the straight- and bent-culm variants of D. sinicus, respectively, and studied how the domains I, i, and II of DsIAA21 affect the gene transcriptional repression. The results showed that bIAA21 expression was rapidly induced by exogenous auxin in D. sinicus. In transgenic tobacco, sIAA21 and bIAA21 mutated in domains i, and II significantly regulated plant architecture and root development. Stem cross sections revealed that parenchyma cells were smaller in transgenic plants than that in wild type plants. Domain i mutation changed the leucine and proline at position 45 to proline and leucine (siaa21L45P and biaa21P45L) strongly repressed cell expansion and root elongation by reducing the gravitropic response. Substitution of isoleucine with valine in domain II of the full length DsIAA21 resulted in dwarf stature in transgenic tobacco plants. Furthermore, the DsIAA21 interacted with auxin response factor 5 (ARF5) in transgenic tobacco plants, suggesting that DsIAA21 might inhibit stem and root elongation via interacting with ARF5. Taken together, our data indicated that DsIAA21 was a negative regulator of plant development and suggested that amino acid differences in domain i of sIAA21 versus bIAA21 affected their response to auxin, and might play a key role in the formation of the bent culm variant in D. sinicus. Our results not only shed a light on the morphogenetic mechanism in D. sinicus, but also provided new insights into versatile function of Aux/IAAs in plants.


Asunto(s)
Factor V , Nicotiana , Nicotiana/genética , Nicotiana/metabolismo , Factor V/genética , Factor V/metabolismo , Leucina/genética , Leucina/metabolismo , Ácidos Indolacéticos/metabolismo , Mutación/genética , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/metabolismo , Regulación de la Expresión Génica de las Plantas
10.
Sensors (Basel) ; 22(23)2022 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-36501985

RESUMEN

In space gravitational-wave-detection missions, inertial sensors are used as the core loads, and their acceleration noise needs to reach 3×10−15 ms−2/Hz at a frequency of 0.1 mHz, which corresponds to the capacitive sensing system; the capacitive sensing noise on the sensitive axis needs to reach 1 aF/Hz. Unlike traditional circuit noise evaluation, the noise in the mHz frequency band is dominated by the thermal noise and the 1/f noise of the device, which is a challenging technical goal. In this paper, a low-frequency, high-precision resonant capacitor bridge method based on a planar transformer is used. Compared with the traditional winding transformer, the developed planar transformer has the advantages of low temperature drift and low 1/f noise. For closed-loop measurements of capacitive sensing circuits and sensitive structures, the minimum capacitive resolution in the time domain is about 3 aF, which is far lower than the scientific measurement resolution requirement of 5.8 fF for gravitational wave detection. The capacitive sensing noise is converted to 1.095 aF/Hz in the frequency band of 10 mHz−1 Hz. Although there is a gap between the closed-loop measurement results and the final index, the measurement environment is an experimental condition without temperature control on the ground; additionally, in China, the measurement integrity and actual measurement results of the capacitive sensing function have reached a domestic leading level. This is the realization of China's future space gravitational wave exploration.

11.
Nat Commun ; 13(1): 6936, 2022 11 14.
Artículo en Inglés | MEDLINE | ID: mdl-36376288

RESUMEN

Human infections with H7N9 avian influenza A virus that emerged in East China in 2013 and caused high morbidity rates were more frequently detected in men than in women over the last five epidemic waves. However, molecular markers associated with poor disease outcomes in men are still unknown. In this study, we systematically analysed sex hormone and cytokine levels in males and females with laboratory-confirmed H7N9 influenza in comparison to H7N9-negative control groups as well as laboratory-confirmed seasonal H1N1/H3N2 influenza cases (n = 369). Multivariable analyses reveal that H7N9-infected men present with considerably reduced testosterone levels associated with a poor outcome compared to non-infected controls. Regression analyses reveal that testosterone levels in H7N9-infected men are negatively associated with the levels of several pro-inflammatory cytokines, such as IL-6 and IL-15. To assess whether there is a causal relationship between low testosterone levels and avian H7N9 influenza infection, we used a mouse model. In male mice, we show that respiratory H7N9 infection leads to a high viral load and inflammatory cytokine response in the testes as well as a reduction in pre-infection plasma testosterone levels. Collectively, these findings suggest that monitoring sex hormone levels may support individualized management for patients with avian influenza infections.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A , Subtipo H7N9 del Virus de la Influenza A , Gripe Aviar , Gripe Humana , Humanos , Masculino , Femenino , Animales , Ratones , Subtipo H3N2 del Virus de la Influenza A , Testosterona , Citocinas , China/epidemiología
12.
Opt Express ; 30(10): 15951-15962, 2022 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-36221449

RESUMEN

With a three-dimensional classical ensemble method, we theoretically investigated the correlated electron dynamics in nonsequential double ionization (NSDI) driven by the spatially inhomogeneous fields. Our results show that NSDI in the spatially inhomogeneous fields is more efficient than that in the spatially homogeneous fields at the low laser intensities, while at the high intensities NSDI is suppressed as compared to the homogeneous fields. More interestingly, our results show that the electron pairs from NSDI exhibit a much stronger angular correlation in the spatially inhomogeneous fields, especially at the higher laser intensities. The correlated electron momentum distribution shows that in the inhomogeneous fields the electron pairs favor to achieve the same final momentum, and the distributions dominantly are clustered in the more compact regions. It is shown that the electron's momentum is focused by the inhomogeneous fields. The underlying dynamics is revealed by back-tracing the classical trajectories.

13.
Biochem Biophys Res Commun ; 589: 63-70, 2022 01 22.
Artículo en Inglés | MEDLINE | ID: mdl-34891043

RESUMEN

Psoriasiform skin inflammation is the common chronic skin inflammatory disease with no effective clinical therapy. Salubrinal is a multifunctional molecule playing a protective role in several conditions. Recently, studies have reported that Salubrinal is a potential therapeutic agent for inflammatory diseases. However, the protective role of Salubrinal in psoriasis-like skin inflammation remains unknown. In this article, imiquimod (IMQ)-induced psoriasis models were established in wild-type mice to explore the role of Salubrinal in the development of psoriasis. As a result, the IMQ-induced mouse models exhibited typical skin inflammation, which was alleviated by the administration of Salubrinal. Furthermore, RAW264.7 macrophage was stimulated with Lipopolysaccharide(LPS) in the presence or absence of Salubrinal. LPS stimulation elevated the expression of various inflammatory biomarkers, while the administration of Salubrinal abolished the function of LPS in RAW264.7 macrophages. In addition, the activation of the nuclear factor-kappa B (NF-κB) signaling pathway in both the LPS-stimulated RAW264.7 macrophage and psoriasis mouse models was antagonized by the administration of Salubrinal. Collectively, Salubrinal might be considered as a promising therapeutic agent for psoriasis-like skin inflammation.


Asunto(s)
Cinamatos/farmacología , Inflamación/patología , Macrófagos/metabolismo , Macrófagos/patología , FN-kappa B/metabolismo , Sustancias Protectoras/farmacología , Psoriasis/patología , Piel/patología , Tiourea/análogos & derivados , Animales , Modelos Animales de Enfermedad , Imiquimod/efectos adversos , Inflamación/tratamiento farmacológico , Macrófagos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Sustancias Protectoras/uso terapéutico , Psoriasis/tratamiento farmacológico , Células RAW 264.7 , Transducción de Señal/efectos de los fármacos , Tiourea/farmacología , Factor de Necrosis Tumoral alfa
14.
Heliyon ; 8(12): e12600, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36593818

RESUMEN

Transcription factors (TFs) play indispensable roles in plant development and stress responses. As the largest woody bamboo species in the world, Dendrocalamus sinicus is endemic to Yunnan Province, China, and possesses two natural variants characterized by culm shape, namely straight or bent culms. Understanding the transcriptional regulation network of D. sinicus provides a unique opportunity to clarify the growth and development characteristics of woody bamboos. In this study, 10,236 TF transcripts belonging to 57 families were identified from transcriptome data of two variants at different developmental stages, from which we constructed a transcriptional regulatory network and unigene-coding protein-TFs interactive network of culm development for this attractive species. Gene function enrichment analysis revealed that hormone signaling and MAPK signaling pathways were two most enriched pathways in TF-regulated network. Based on PPI analysis, 50 genes interacting with nine TFs were screened as the core regulation components related to culm development. Of them, 18 synergistic genes of seven TFs, including nuclear cap-binding protein subunit 1, transcription factor GTE9-like, and ATP-dependent DNA helicase DDX11 isoform X1, involved in culm-shape variation. Most of these genes would interact with MYB, C3H, and ARF transcription factors. Six members with two each from ARF, C3H, and MYB transcription factor families and six key interacting genes (IAA3, IAA19, leucine-tRNA ligase, nuclear cap-binding protein subunit 1, elongation factor 2, and coiled-coil domain-containing protein 94) cooperate with these transcription factors were differentially expressed at development stage of young culms, and were validated by quantitative PCR. Our results represent a crucial step towards understanding the regulatory mechanisms of TFs involved in culm development and variation of D. sinicus.

15.
Front Vet Sci ; 8: 740472, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34746280

RESUMEN

Wild aquatic birds are the primary natural reservoir of influenza A viruses (IAVs), although a small number of viruses can spill over to mammals and circulate. The focus of IAV infection in mammals was largely limited to humans and swine variants, until the emergence of H3N2 canine influenza viruses (CIVs), which provides new perspective for interspecies transmission of the virus. In this study, we captured 54 canine-adaptive signatures in H3N2 CIVs through entropy computation, which were largely concentrated in the interaction region of polymerase proteins on ribonucleoprotein complex. The receiver operating characteristic curves of these sites showed >95% accuracy in distinguishing between the hosts. Nine of the 54 canine-adaptive signatures were shared in avian-human/equine or equine-canine (PB2-82; PB1-361; PA-277; HA-81, 111, 172, 196, 222, 489), suggesting their involvement in canine adaptation. Furthermore, we found that IAVs can establish persistent transmission in lower mammals with greater ease compared to higher mammals, and 25 common adaptation signatures of H3 IAVs were observed in diverse avian-mammals comparison. There were few human-like residues in H3N2 CIVs, which suggested a low risk of human infection. Our study highlights the necessity of identifying and monitoring the emerging adaptive mutations in companion animals by enhanced surveillance and provides a basis for mammal adaptation of avian influenza viruses.

16.
Science ; 373(6557): 918-922, 2021 08 20.
Artículo en Inglés | MEDLINE | ID: mdl-34413236

RESUMEN

Zoonotic avian influenza A virus (IAV) infections are rare. Sustained transmission of these IAVs between humans has not been observed, suggesting a role for host genes. We used whole-genome sequencing to compare avian IAV H7N9 patients with healthy controls and observed a strong association between H7N9 infection and rare, heterozygous single-nucleotide variants in the MX1 gene. MX1 codes for myxovirus resistance protein A (MxA), an interferon-induced antiviral guanosine triphosphatase known to control IAV infections in transgenic mice. Most of the MxA variants identified lost the ability to inhibit avian IAVs, including H7N9, in transfected human cell lines. Nearly all of the inactive MxA variants exerted a dominant-negative effect on the antiviral function of wild-type MxA, suggesting an MxA null phenotype in heterozygous carriers. Our study provides genetic evidence for a crucial role of the MX1-based antiviral defense in controlling zoonotic IAV infections in humans.


Asunto(s)
Subtipo H7N9 del Virus de la Influenza A , Gripe Humana/genética , Gripe Humana/virología , Proteínas de Resistencia a Mixovirus/genética , Enfermedades de los Trabajadores Agrícolas/genética , Enfermedades de los Trabajadores Agrícolas/virología , Animales , Línea Celular , Predisposición Genética a la Enfermedad , Variación Genética , Heterocigoto , Humanos , Subtipo H7N9 del Virus de la Influenza A/fisiología , Virus de la Influenza A/fisiología , Mutación Missense , Proteínas de Resistencia a Mixovirus/química , Proteínas de Resistencia a Mixovirus/metabolismo , Aves de Corral , Zoonosis Virales , Secuenciación Completa del Genoma
17.
Emerg Microbes Infect ; 10(1): 123-131, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33393450

RESUMEN

Influenza A(H1N1)pdm09 virus has remained in a seasonal circulation since being recognized in 2009. Although it followed a mild course in most patients, in others it caused a series of severe clinical illnesses. Epidemiologic studies have implicated that host factors have a major influence on the disease severity of influenza A(H1N1)pdm09 infection. However, an understanding of relevant genetic variations and the underlying mechanisms is still limited. In this present study, we used a host-based whole genome sequencing (WGS) method to comprehensively explore the genetic risk loci associated with severity of influenza A(H1N1)pdm09 infection. From the common single-nucleotide variants (SNVs) analysis, we identified the abnormal nominally significant (P < 1 × 10-4) common SNVs enriched in PTBP3 gene. The results of rare functional SNVs analysis supported that there were several novel candidate genes might confer risk of severe influenza A(H1N1)pdm09 diseases, such as FTSJ3, CPVL, BST2, NOD2 and MAVS. Moreover, our results of gene set based analysis indicated that the HIF-1 transcription factor and IFN-γ pathway might play an important role in the underlying mechanism of severe influenza A(H1N1)pdm09. These findings will increase our knowledge about biological mechanism underlying the severe influenza A(H1N1)pdm09 and facilitate to design novel personalized treatments.


Asunto(s)
Redes Reguladoras de Genes , Subtipo H1N1 del Virus de la Influenza A/patogenicidad , Gripe Humana/virología , Polimorfismo de Nucleótido Simple , Secuenciación Completa del Genoma/métodos , Niño , Preescolar , Femenino , Estudios de Asociación Genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Lactante , Gripe Humana/genética , Masculino , Medicina de Precisión , Índice de Severidad de la Enfermedad
18.
Emerg Microbes Infect ; 9(1): 1853-1863, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32746754

RESUMEN

Influenza B virus (IBV) is one of the most important human respiratory viruses: it causes approximately one-third of the global influenza-related disease burden each year. However, compared with the several pathogenicity-related molecular markers that have been identified for influenza A virus (IAV), little is known about potential IBV pathogenicity-related markers. Here, although the IBV strain B/Anhui-Tunxi/1528/2014 (AH1528/14) exhibited a more efficient replication ability in vitro and higher pathogenicity in vivo compared with IBV strain B/Anhui-Baohe/127/2015 (AH127/15), only three amino acids differences (HAA390E, NAN342D and PB1V212I) were observed among their full genomes. The contributions of each amino acid difference to the virus pathogenicity were further investigated. Compared with the wild type IBV virus rAH127, the recombinant virus harbouring a single substitution of HAA390E had a similar phenotype, whereas the recombinant virus harbouring PB1V212I replicated to a moderately higher titre in both MDCK cells and in mice. Notably, the virus harbouring NAN342D showed significantly better growth properties in MDCK cells and higher fatality rates in mice. In addition, the presence of NAN342D dramatically enhanced the viral neuraminidase activity. In conclusion, our study identified a novel IBV molecular marker, NAN342D, that could significantly increase the virulence of IBV in mice.


Asunto(s)
Virus de la Influenza B/patogenicidad , Neuraminidasa/genética , Infecciones por Orthomyxoviridae/patología , Virus Reordenados/patogenicidad , Proteínas Virales/genética , Secuencia de Aminoácidos/genética , Animales , Línea Celular , Perros , Femenino , Genoma Viral/genética , Células HEK293 , Humanos , Virus de la Influenza B/genética , Células de Riñón Canino Madin Darby , Ratones , Ratones Endogámicos C57BL , Infecciones por Orthomyxoviridae/virología , Virus Reordenados/genética , Replicación Viral/genética
19.
Sci Rep ; 10(1): 11768, 2020 07 16.
Artículo en Inglés | MEDLINE | ID: mdl-32678187

RESUMEN

The A(H7N9) virus strain that emerged in 2013 was associated with a high fatality rate and may become a long-term threat to public health. A(H7N9) disease incidence is disproportionate to viral exposure, suggesting that host genetic factors may significantly influence susceptibility to A(H7N9) infection. Human genome variation in conferring risk for A(H7N9) infection in Chinese populations was identified by a two-stage investigation involving 121 A(H7N9) patients and 187 healthy controls using next generation sequencing followed by functional analysis. As a result, a low frequency variant (rs189256251; P = 0.0303, OR = 3.45, 95% CI 1.05-11.35, chi-square test) and three HLA alleles (DQB1*06:01, DQA1*05:05 and C*12:02) were identified in A(H7N9) infected volunteers. In an A549 cell line carrying the rs189256251 variant CT genotype, A(H7N9) infection incidence was elevated 6.665-fold over control cells carrying the CC genotype. Serum levels of interferon alpha were significantly lower in patients with the CT genotype compared to the CC genotype (P = 0.01). The study findings of genetic predisposition to A(H7N9) in the Chinese population may be valuable in systematic investigations of A(H7N9) disease etiology.


Asunto(s)
Sitios Genéticos , Predisposición Genética a la Enfermedad , Interacciones Huésped-Patógeno , Subtipo H7N9 del Virus de la Influenza A , Gripe Humana/genética , Gripe Humana/virología , Adulto , Alelos , Frecuencia de los Genes , Genotipo , Secuenciación de Nucleótidos de Alto Rendimiento , Interacciones Huésped-Patógeno/genética , Humanos , Masculino
20.
Int J Mol Sci ; 21(1)2019 Dec 25.
Artículo en Inglés | MEDLINE | ID: mdl-31881689

RESUMEN

Potato is an important food crop and its production is susceptible to drought. Drought stress in crop growth is usually multiple- or long-term. In this study, the drought tolerant potato landrace Jancko Sisu Yari was treated with drought stress, rehydration and re-dehydration, and RNA-seq was applied to analyze the characteristics of gene regulation during these treatments. The results showed that drought-responsive genes mainly involved photosynthesis, signal transduction, lipid metabolism, sugar metabolism, wax synthesis, cell wall regulation, osmotic adjustment. Potato also can be recovered well in the re-emergence of water through gene regulation. The recovery of rehydration mainly related to patatin, lipid metabolism, sugar metabolism, flavonoids metabolism and detoxification besides the reverse expression of the most of drought-responsive genes. The previous drought stress can produce a positive responsive ability to the subsequent drought by drought hardening. Drought hardening was not only reflected in the drought-responsive genes related to the modified structure and cell components, but also in the hardening of gene expression or the "memory" of drought-responsive genes. Abundant genes involved photosynthesis, signal transduction, sugar metabolism, protease and protease inhibitors, flavonoids metabolism, transporters and transcription factors were subject to drought hardening or memorized drought in potato.


Asunto(s)
Sequías , Solanum tuberosum/metabolismo , Transcriptoma , Agua/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , ARN de Planta/química , ARN de Planta/metabolismo , Solanum tuberosum/genética
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