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1.
Methods Mol Biol ; 2212: 1-15, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33733346

RESUMEN

A mass-based protein phylogeny method, known as phylonumerics, is described to build phylogenetic-like trees using a purpose-built MassTree algorithm. These trees are constructed from sets of numerical mass map data for each protein without the need for gene or protein sequences. Such trees have been shown to be highly congruent with conventional sequence-based trees and provide a reliable means to study the evolutionary history of organisms. Mutations determined from the differences in the mass of peptide pairs across different mass sets are computed by the algorithm and displayed at branch nodes across the tree. By definition, since the trees display a phylogeny representing expressed proteins, all mutations are non-synonymous. The frequency of these mutations and a mutation score based on a sum of these frequencies weighted based upon their position to the root of the tree are output. The algorithm also outputs lists of pairs of mutations separated along interconnected branches of the tree. Those which co-occur or which occur consecutively, or near consecutively, and that are separated by a distance less than the average distance for all mutation pairs, are putatively assigned to be epistatic pairs. These pairs are examined further with a focus on non-conservative substitutions given their importance in driving structural and functional change and protein and organismal evolution. The application of the method is demonstrated for the H3 hemagglutinin protein of type A human H3N2 strains of the influenza virus. The most frequent ancestral mutations within epistatic pairs occur within antigenic site domains while the descendant mutations occur either at other antigenic sites or elsewhere in the protein. Both predominate at reported glycosylation sites. The results for this protein further support a "small steps" evolutionary model for the influenza virus where non-conservative mutations that involve the least structural change are favored over those involving substantive change, which may risk the virus's own extinction.


Asunto(s)
Epistasis Genética , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Subtipo H3N2 del Virus de la Influenza A/genética , Gripe Humana/virología , Algoritmos , Glicoproteínas Hemaglutininas del Virus de la Influenza/metabolismo , Humanos , Subtipo H3N2 del Virus de la Influenza A/metabolismo , Subtipo H3N2 del Virus de la Influenza A/patogenicidad , Gripe Humana/patología , Mutación , Filogenia , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción
2.
Nat Commun ; 12(1): 1722, 2021 03 19.
Artículo en Inglés | MEDLINE | ID: mdl-33741916

RESUMEN

Broadly neutralizing antibodies (bnAbs) have been developed as potential countermeasures for seasonal and pandemic influenza. Deep characterization of these bnAbs and polyclonal sera provides pivotal understanding for influenza immunity and informs effective vaccine design. However, conventional virus neutralization assays require high-containment laboratories and are difficult to standardize and roboticize. Here, we build a panel of engineered influenza viruses carrying a reporter gene to replace an essential viral gene, and develop an assay using the panel for in-depth profiling of neutralizing antibodies. Replication of these viruses is restricted to cells expressing the missing viral gene, allowing it to be manipulated in a biosafety level 2 environment. We generate the neutralization profile of 24 bnAbs using a 55-virus panel encompassing the near-complete diversity of human H1N1 and H3N2, as well as pandemic subtype viruses. Our system offers in-depth profiling of influenza immunity, including the antibodies against the hemagglutinin stem, a major target of universal influenza vaccines.


Asunto(s)
Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Virus de la Influenza A/inmunología , Gripe Humana/virología , Antígenos Virales/inmunología , Perfilación de la Expresión Génica , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Hemaglutininas , Humanos , Inmunidad , Subtipo H1N1 del Virus de la Influenza A/inmunología , Subtipo H3N2 del Virus de la Influenza A/inmunología , Virus de la Influenza A/genética , Vacunas contra la Influenza/inmunología , Infecciones por Orthomyxoviridae/virología , Filogenia
3.
Virol J ; 18(1): 64, 2021 03 25.
Artículo en Inglés | MEDLINE | ID: mdl-33766078

RESUMEN

BACKGROUND: Variation in host genetic factors may result in variation in the host immune response to the infection. Some chronic diseases may also affect individuals' susceptibility to infectious diseases. The aim of this study was to evaluate the association of the host genetic factors mostly involved in inflammation, as well as hypercholesterolemia and diabetes with mild flu in an Iranian population. METHODS: In this cross-sectional study, nasopharyngeal swab samples were collected from 93 patients referred to primary care centers of Markazi, Semnan, and Zanjan provinces (central Iran) due to flu-like symptoms between March 2015 and December 2018. Of these, PCR test identified 49 influenza A/H1N1 and 44 flu-negative individuals. Twelve single-nucleotide polymorphisms (SNPs) in RPAIN, FCGR2A, MBL-2, CD55, C1QBP, IL-10, TNF-α and an unknown gene were genotyped using iPLEX GOLD SNP genotyping analysis. Hypercholesterolemia and diabetes status was determined based on the physician diagnosis. Association of the host genetic variants, hypercholesterolemia and diabetes with mild A/H1N1 flu was assessed with univariable and multivariable logistic regression analysis as implemented in Stata software (v.14). Statistical tests were considered as significant at 0.05 levels. RESULTS: Frequency of diabetes and hypercholesterolemia, as well as participants mean age was significantly higher in the flu-negative rather than the flu-positive group. Of 12 SNPs, nine did not show any significant association with mild flu in our study (rs1801274, rs1800451, rs2564978, rs361525, rs1800450, rs1800871, rs1800872, rs1800896, rs1800629). Possessing G vs. A allele in two SNPs (rs3786054 and rs8070740) was associated with a threefold increase in the chance of mild flu when compared to flu-negative patients (95% CI: 1.1, 22.0). Possessing C allele (vs. A) in the rs9856661 locus also increased the chance of mild flu up to 2 folds (95% CI: 1.0, 10.0). CONCLUSION: The results showed that possessing the G allele in either rs3786054 or rs8070740 loci in C1QBP and RPAIN genes, respectively, increased the risk of H1N1 infection up to 3.3 folds, regardless of the patient's age, BMI, diabetes, and hypercholesterolemia. Complementary functional genomic studies would shed more light on the underlying mechanism of human immunity associated with these genetic markers. The identified genetic factors may have the same role in susceptibility to similar respiratory infections with RNA viruses, like SARS, MERS and COVID-19. Future genetic association studies targeting these RNA viruses, especially COVID-19 is recommended. Studies on other ethnic groups would also shed light on possible ethnic variations in genetic susceptibility to respiratory RNA viruses. Trial registry IR.PII.REC.1399.063.


Asunto(s)
Diabetes Mellitus/genética , Diabetes Mellitus/virología , Estudios de Asociación Genética , Hipercolesterolemia/genética , Hipercolesterolemia/virología , Gripe Humana/genética , Gripe Humana/virología , Adulto , Anciano , Alelos , Estudios Transversales , Diabetes Mellitus/epidemiología , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Hipercolesterolemia/epidemiología , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/epidemiología , Irán/epidemiología , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Análisis de Regresión , Adulto Joven
4.
Nat Commun ; 12(1): 1914, 2021 03 26.
Artículo en Inglés | MEDLINE | ID: mdl-33772013

RESUMEN

Innate immunity is important for host defense by eliciting rapid anti-viral responses and bridging adaptive immunity. Here, we show that endogenous lipids released from virus-infected host cells activate lung γδ T cells to produce interleukin 17 A (IL-17A) for early protection against H1N1 influenza infection. During infection, the lung γδ T cell pool is constantly supplemented by thymic output, with recent emigrants infiltrating into the lung parenchyma and airway to acquire tissue-resident feature. Single-cell studies identify IL-17A-producing γδ T (Tγδ17) cells with a phenotype of TCRγδhiCD3hiAQP3hiCXCR6hi in both infected mice and patients with pneumonia. Mechanistically, host cell-released lipids during viral infection are presented by lung infiltrating CD1d+ B-1a cells to activate IL-17A production in γδ T cells via γδTCR-mediated IRF4-dependent transcription. Reduced IL-17A production in γδ T cells is detected in mice either lacking B-1a cells or with ablated CD1d in B cells. Our findings identify a local host-immune crosstalk and define important cellular and molecular mediators for early innate defense against lung viral infection.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A/inmunología , Gripe Humana/inmunología , Lípidos/inmunología , Infecciones por Orthomyxoviridae/inmunología , Receptores de Antígenos de Linfocitos T gamma-delta/inmunología , Animales , Antígenos CD1d/inmunología , Antígenos CD1d/metabolismo , Femenino , Interacciones Huésped-Patógeno/inmunología , Humanos , Inmunidad Innata/inmunología , Subtipo H1N1 del Virus de la Influenza A/fisiología , Gripe Humana/metabolismo , Gripe Humana/virología , Factores Reguladores del Interferón/inmunología , Factores Reguladores del Interferón/metabolismo , Interleucina-17/inmunología , Interleucina-17/metabolismo , Pulmón/inmunología , Pulmón/metabolismo , Pulmón/virología , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Infecciones por Orthomyxoviridae/metabolismo , Infecciones por Orthomyxoviridae/virología , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo
5.
Molecules ; 26(4)2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33672072

RESUMEN

Calcium (Ca2+) dependent signaling circuit plays a critical role in influenza A virus (IAV) infection. The 8-O-(E-p-methoxycinnamoyl)harpagide (MCH) exhibits pharmacological activities that exert neuroprotective, hepatoprotective, anti-inflammatory and other biological effects. However, not have reports of antiviral effects. To investigate the antiviral activity of MCH on IAV-infected human lung cells mediated by calcium regulation. We examined the inhibitory effect of MCH on IAV infections and measured the level of viral proteins upon MCH treatment using Western blotting. We also performed molecular docking simulation with MCH and IAV M2 protein. Finally, we analyzed MCH's suppression of intracellular calcium and ROS (reactive oxygen species) in IAV-infected human lung cells using a flow cytometer. The results shown that MCH inhibited the infection of IAV and increased the survival of the infected human lung cells. The levels of IAV protein M1, M2, NS1 and PA were inhibited in MCH-treated human lung cells compared to that in infected and untreated cells. Also, docking simulation suggest that MCH interacted with M2 on its hydrophobic wall (L40 and I42) and polar amino acids (D44 and R45), which formed intermolecular contacts and were a crucial part of the channel gate along with W41. Lastly, MCH inhibited IAV infection by reducing intracellular calcium and mitochondrial Ca2+/ROS levels in infected human lung cells. Taken together, these data suggest that MCH inhibits IAV infection and increases the survival of infected human lung cells by suppressing calcium levels. These results indicate that MCH is useful for developing IAV treatments.


Asunto(s)
Antivirales/farmacología , Calcio/metabolismo , Virus de la Influenza A/efectos de los fármacos , Espacio Intracelular/metabolismo , Glicósidos Iridoides/farmacología , Piranos/farmacología , Células A549 , Antivirales/uso terapéutico , Humanos , Gripe Humana/tratamiento farmacológico , Gripe Humana/virología , Canales Iónicos/metabolismo , Glicósidos Iridoides/química , Glicósidos Iridoides/uso terapéutico , Mitocondrias/efectos de los fármacos , Mitocondrias/patología , Simulación del Acoplamiento Molecular , Piranos/química , Piranos/uso terapéutico , Proteínas de la Matriz Viral
6.
Front Immunol ; 12: 629193, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33732251

RESUMEN

Hyper-induction of pro-inflammatory cytokines, also known as a cytokine storm or cytokine release syndrome (CRS), is one of the key aspects of the currently ongoing SARS-CoV-2 pandemic. This process occurs when a large number of innate and adaptive immune cells activate and start producing pro-inflammatory cytokines, establishing an exacerbated feedback loop of inflammation. It is one of the factors contributing to the mortality observed with coronavirus 2019 (COVID-19) for a subgroup of patients. CRS is not unique to the SARS-CoV-2 infection; it was prevalent in most of the major human coronavirus and influenza A subtype outbreaks of the past two decades (H5N1, SARS-CoV, MERS-CoV, and H7N9). With a comprehensive literature search, we collected changing the cytokine levels from patients upon infection with the viral pathogens mentioned above. We analyzed published patient data to highlight the conserved and unique cytokine responses caused by these viruses. Our curation indicates that the cytokine response induced by SARS-CoV-2 is different compared to other CRS-causing respiratory viruses, as SARS-CoV-2 does not always induce specific cytokines like other coronaviruses or influenza do, such as IL-2, IL-10, IL-4, or IL-5. Comparing the collated cytokine responses caused by the analyzed viruses highlights a SARS-CoV-2-specific dysregulation of the type-I interferon (IFN) response and its downstream cytokine signatures. The map of responses gathered in this study could help specialists identify interventions that alleviate CRS in different diseases and evaluate whether they could be used in the COVID-19 cases.


Asunto(s)
/inmunología , Síndrome de Liberación de Citoquinas/inmunología , Virus de la Influenza A/inmunología , Gripe Humana/inmunología , Coronavirus del Síndrome Respiratorio de Oriente Medio/inmunología , Virus del SRAS/inmunología , Síndrome Respiratorio Agudo Grave/inmunología , Índice de Severidad de la Enfermedad , /sangre , /virología , Síndrome de Liberación de Citoquinas/sangre , Síndrome de Liberación de Citoquinas/virología , Citocinas/sangre , Humanos , Inflamación/inmunología , Gripe Humana/sangre , Gripe Humana/virología , Síndrome Respiratorio Agudo Grave/sangre , Síndrome Respiratorio Agudo Grave/virología
7.
Sci Transl Med ; 13(583)2021 03 03.
Artículo en Inglés | MEDLINE | ID: mdl-33658355

RESUMEN

Seasonal influenza vaccines confer protection against specific viral strains but have restricted breadth that limits their protective efficacy. The H1 and H3 subtypes of influenza A virus cause most of the seasonal epidemics observed in humans and are the major drivers of influenza A virus-associated mortality. The consequences of pandemic spread of COVID-19 underscore the public health importance of prospective vaccine development. Here, we show that headless hemagglutinin (HA) stabilized-stem immunogens presented on ferritin nanoparticles elicit broadly neutralizing antibody (bnAb) responses to diverse H1 and H3 viruses in nonhuman primates (NHPs) when delivered with a squalene-based oil-in-water emulsion adjuvant, AF03. The neutralization potency and breadth of antibodies isolated from NHPs were comparable to human bnAbs and extended to mismatched heterosubtypic influenza viruses. Although NHPs lack the immunoglobulin germline VH1-69 residues associated with the most prevalent human stem-directed bnAbs, other gene families compensated to generate bnAbs. Isolation and structural analyses of vaccine-induced bnAbs revealed extensive interaction with the fusion peptide on the HA stem, which is essential for viral entry. Antibodies elicited by these headless HA stabilized-stem vaccines neutralized diverse H1 and H3 influenza viruses and shared a mode of recognition analogous to human bnAbs, suggesting that these vaccines have the potential to confer broadly protective immunity against diverse viruses responsible for seasonal and pandemic influenza infections in humans.


Asunto(s)
Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Vacunas contra la Influenza/inmunología , Primates/inmunología , Animales , Anticuerpos Antivirales/biosíntesis , Anticuerpos Antivirales/química , Complejo Antígeno-Anticuerpo/química , Anticuerpos ampliamente neutralizantes/biosíntesis , Anticuerpos ampliamente neutralizantes/química , Ferritinas/química , Ferritinas/inmunología , Glicoproteínas Hemaglutininas del Virus de la Influenza/química , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Humanos , Vacunas contra la Influenza/administración & dosificación , Vacunas contra la Influenza/química , Gripe Humana/inmunología , Gripe Humana/virología , Macaca fascicularis , Modelos Moleculares , Nanopartículas/química , Pandemias , Primates/virología , Estructura Cuaternaria de Proteína , Investigación en Medicina Traslacional
8.
Molecules ; 26(4)2021 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-33562349

RESUMEN

As a member of the Orthomyxoviridae family of viruses, influenza viruses (IVs) are known causative agents of respiratory infection in vertebrates. They remain a major global threat responsible for the most virulent diseases and global pandemics in humans. The virulence of IVs and the consequential high morbidity and mortality of IV infections are primarily attributed to the high mutation rates in the IVs' genome coupled with the numerous genomic segments, which give rise to antiviral resistant and vaccine evading strains. Current therapeutic options include vaccines and small molecule inhibitors, which therapeutically target various catalytic processes in IVs. However, the periodic emergence of new IV strains necessitates the continuous development of novel anti-influenza therapeutic options. The crux of this review highlights the recent studies on the biology of influenza viruses, focusing on the structure, function, and mechanism of action of the M2 channel and neuraminidase as therapeutic targets. We further provide an update on the development of new M2 channel and neuraminidase inhibitors as an alternative to existing anti-influenza therapy. We conclude by highlighting therapeutic strategies that could be explored further towards the design of novel anti-influenza inhibitors with the ability to inhibit resistant strains.


Asunto(s)
Gripe Humana/tratamiento farmacológico , Orthomyxoviridae/efectos de los fármacos , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Proteínas de la Matriz Viral/genética , Farmacorresistencia Viral/efectos de los fármacos , Inhibidores Enzimáticos/uso terapéutico , Humanos , Gripe Humana/virología , Neuraminidasa/antagonistas & inhibidores , Neuraminidasa/genética , Orthomyxoviridae/genética , Infecciones del Sistema Respiratorio/patología , Infecciones del Sistema Respiratorio/virología , Proteínas de la Matriz Viral/antagonistas & inhibidores
9.
Nat Commun ; 12(1): 1001, 2021 02 12.
Artículo en Inglés | MEDLINE | ID: mdl-33579926

RESUMEN

Stringent nonpharmaceutical interventions (NPIs) such as lockdowns and border closures are not currently recommended for pandemic influenza control. New Zealand used these NPIs to eliminate coronavirus disease 2019 during its first wave. Using multiple surveillance systems, we observed a parallel and unprecedented reduction of influenza and other respiratory viral infections in 2020. This finding supports the use of these NPIs for controlling pandemic influenza and other severe respiratory viral threats.


Asunto(s)
/epidemiología , Gripe Humana/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , /prevención & control , Control de Enfermedades Transmisibles , Monitoreo Epidemiológico , Hospitalización/estadística & datos numéricos , Humanos , Gripe Humana/prevención & control , Gripe Humana/virología , Nueva Zelanda/epidemiología , Pandemias , Salud Pública , Infecciones del Sistema Respiratorio/prevención & control , Infecciones del Sistema Respiratorio/virología , /aislamiento & purificación
10.
JCI Insight ; 6(6)2021 03 22.
Artículo en Inglés | MEDLINE | ID: mdl-33600379

RESUMEN

Regulatory T (Treg) cells orchestrate resolution and repair of acute lung inflammation and injury after viral pneumonia. Compared with younger patients, older individuals experience impaired recovery and worse clinical outcomes after severe viral infections, including influenza and SARS coronavirus 2 (SARS-CoV-2). Whether age is a key determinant of Treg cell prorepair function after lung injury remains unknown. Here, we showed that aging results in a cell-autonomous impairment of reparative Treg cell function after experimental influenza pneumonia. Transcriptional and DNA methylation profiling of sorted Treg cells provided insight into the mechanisms underlying their age-related dysfunction, with Treg cells from aged mice demonstrating both loss of reparative programs and gain of maladaptive programs. Strategies to restore youthful Treg cell functional programs could be leveraged as therapies to improve outcomes among older individuals with severe viral pneumonia.


Asunto(s)
Envejecimiento/fisiología , Virus de la Influenza A , Gripe Humana/patología , Pulmón/patología , Neumonía Viral/patología , Linfocitos T Reguladores/patología , Factores de Edad , Envejecimiento/metabolismo , Animales , /metabolismo , /virología , Humanos , Gripe Humana/complicaciones , Gripe Humana/metabolismo , Gripe Humana/virología , Pulmón/metabolismo , Ratones Endogámicos C57BL , Neumonía Viral/etiología , Neumonía Viral/metabolismo , Neumonía Viral/virología , Linfocitos T Reguladores/metabolismo
12.
Sci Adv ; 7(1)2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33523846

RESUMEN

Here, we report the topology-matched design of heteromultivalent nanostructures as potent and broad-spectrum virus entry inhibitors based on the host cell membrane. Initially, we investigate the virus binding dynamics to validate the better binding performance of the heteromultivalent moieties as compared to homomultivalent ones. The heteromultivalent binding moieties are transferred to nanostructures with a bowl-like shape matching the viral spherical surface. Unlike the conventional homomultivalent inhibitors, the heteromultivalent ones exhibit a half maximal inhibitory concentration of 32.4 ± 13.7 µg/ml due to the synergistic multivalent effects and the topology-matched shape. At a dose without causing cellular toxicity, >99.99% reduction of virus propagation has been achieved. Since multiple binding sites have also been identified on the S protein of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), we envision that the use of heteromultivalent nanostructures may also be applied to develop a potent inhibitor to prevent coronavirus infection.


Asunto(s)
Glicoproteínas Hemaglutininas del Virus de la Influenza/química , Virus de la Influenza A/efectos de los fármacos , Gripe Humana/virología , Nanopartículas/química , Neuraminidasa/química , Animales , Antivirales/farmacología , Sitios de Unión , Membrana Celular/metabolismo , Perros , Membrana Eritrocítica/virología , Humanos , Virus de la Influenza A/fisiología , Células de Riñón Canino Madin Darby , Unión Proteica , Glicoproteína de la Espiga del Coronavirus , Virión , Acoplamiento Viral/efectos de los fármacos , Internalización del Virus/efectos de los fármacos
13.
Nat Commun ; 12(1): 1203, 2021 02 22.
Artículo en Inglés | MEDLINE | ID: mdl-33619277

RESUMEN

Influenza A virus infection in swine impacts the agricultural industry in addition to its zoonotic potential. Here, we utilize epigraph, a computational algorithm, to design a universal swine H3 influenza vaccine. The epigraph hemagglutinin proteins are delivered using an Adenovirus type 5 vector and are compared to a wild type hemagglutinin and the commercial inactivated vaccine, FluSure. In mice, epigraph vaccination leads to significant cross-reactive antibody and T-cell responses against a diverse panel of swH3 isolates. Epigraph vaccination also reduces weight loss and lung viral titers in mice after challenge with three divergent swH3 viruses. Vaccination studies in swine, the target species for this vaccine, show stronger levels of cross-reactive antibodies and T-cell responses after immunization with the epigraph vaccine compared to the wild type and FluSure vaccines. In both murine and swine models, epigraph vaccination shows superior cross-reactive immunity that should be further investigated as a universal swH3 vaccine.


Asunto(s)
Algoritmos , Reacciones Cruzadas/inmunología , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Inmunidad , Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Animales , Formación de Anticuerpos/inmunología , Epítopos/inmunología , Femenino , Humanos , Gripe Humana/sangre , Gripe Humana/inmunología , Gripe Humana/virología , Pulmón/patología , Pulmón/virología , Masculino , Ratones Endogámicos BALB C , Infecciones por Orthomyxoviridae/sangre , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/prevención & control , Infecciones por Orthomyxoviridae/virología , Porcinos , Linfocitos T/inmunología , Vacunación , Pérdida de Peso
14.
Int J Biol Sci ; 17(2): 539-548, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33613111

RESUMEN

Rationale: Coronavirus disease 2019 (COVID-19) has caused a global pandemic. A classifier combining chest X-ray (CXR) with clinical features may serve as a rapid screening approach. Methods: The study included 512 patients with COVID-19 and 106 with influenza A/B pneumonia. A deep neural network (DNN) was applied, and deep features derived from CXR and clinical findings formed fused features for diagnosis prediction. Results: The clinical features of COVID-19 and influenza showed different patterns. Patients with COVID-19 experienced less fever, more diarrhea, and more salient hypercoagulability. Classifiers constructed using the clinical features or CXR had an area under the receiver operating curve (AUC) of 0.909 and 0.919, respectively. The diagnostic efficacy of the classifier combining the clinical features and CXR was dramatically improved and the AUC was 0.952 with 91.5% sensitivity and 81.2% specificity. Moreover, combined classifier was functional in both severe and non-serve COVID-19, with an AUC of 0.971 with 96.9% sensitivity in non-severe cases, which was on par with the computed tomography (CT)-based classifier, but had relatively inferior efficacy in severe cases compared to CT. In extension, we performed a reader study involving three experienced pulmonary physicians, artificial intelligence (AI) system demonstrated superiority in turn-around time and diagnostic accuracy compared with experienced pulmonary physicians. Conclusions: The classifier constructed using clinical and CXR features is efficient, economical, and radiation safe for distinguishing COVID-19 from influenza A/B pneumonia, serving as an ideal rapid screening tool during the COVID-19 pandemic.


Asunto(s)
/métodos , Gripe Humana/diagnóstico por imagen , Neumonía Viral/diagnóstico por imagen , Radiografía Torácica , Anciano , /fisiopatología , Aprendizaje Profundo , Diagnóstico Diferencial , Humanos , Virus de la Influenza A/aislamiento & purificación , Virus de la Influenza B/aislamiento & purificación , Gripe Humana/fisiopatología , Gripe Humana/virología , Masculino , Persona de Mediana Edad , Pandemias , Neumonía , Neumonía Viral/fisiopatología , Neumonía Viral/virología , Curva ROC , Estudios Retrospectivos , Sensibilidad y Especificidad
15.
Talanta ; 225: 122064, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33592783

RESUMEN

Quantum dots (QDs) based fluorescent nanobeads are considered as promising materials for next generation point-of-care diagnosis systems. In this study, we carried out, for the first time, the synthesis of QDs nanobeads using polystyrene (PS) nanobead as the template. QDs loading on PS nanobead surface in this method can be readily achieved by the use of polyelectrolyte, avoiding the time-consuming and uncontrollable silane reagents-involved functionalization procedure that conventional synthesis of silica-based QDs nanobeads often suffer from. Notably, the application of QDs nanobeads in suspension microarray for H5N1 virus detection leads to a sensitivity lower than 25 PFU/mL. In addition, QDs nanobead was also incorporated into lateral flow assay for SARS-CoV-2 antibody detection, leading to more than one order of magnitude detection sensitivity as compared to that of commercial one based on colloid gold.


Asunto(s)
Técnicas Biosensibles/métodos , Gripe Humana/diagnóstico , Microesferas , Nanoestructuras/química , Poliestirenos/química , Puntos Cuánticos , Anticuerpos Antivirales/inmunología , Colorantes Fluorescentes/química , Humanos , Subtipo H5N1 del Virus de la Influenza A/fisiología , Gripe Humana/virología , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Nanoestructuras/ultraestructura , /fisiología , Sensibilidad y Especificidad , Dióxido de Silicio/química
16.
Arch Virol ; 166(4): 1193-1196, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33580378

RESUMEN

The correlation of viral growth capability (n = 156) with the viral load in nasopharyngeal swabs (n = 76) was assessed. Epidemic influenza A/H1N1, A/H3N2, and B viruses showed a wide range of growth capability (104-1011 copies/mL) in Madin-Darby canine kidney cells. The growth was correlated with the nasopharyngeal viral load (r = 0.53). Six selected strains showed growth-dependent cell death (r = 0.96) in a growth kinetics assay. Epidemic influenza viruses exhibit a wide range of growth capability. Growth capability should be considered one of the key factors in disease prognosis.


Asunto(s)
Epidemias , Gripe Humana/epidemiología , Gripe Humana/virología , Orthomyxoviridae/crecimiento & desarrollo , Células A549 , Animales , Supervivencia Celular , Perros , Humanos , Japón/epidemiología , Células de Riñón Canino Madin Darby , Nasofaringe/virología , Orthomyxoviridae/clasificación , Orthomyxoviridae/genética , Orthomyxoviridae/aislamiento & purificación , Pronóstico , ARN Viral/análisis , Carga Viral
17.
Viruses ; 13(2)2021 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-33540739

RESUMEN

With an estimated three to five million human cases annually and the potential to infect domestic and wild animal populations, influenza viruses are one of the greatest health and economic burdens to our society, and pose an ongoing threat of large-scale pandemics. Despite our knowledge of many important aspects of influenza virus biology, there is still much to learn about how influenza viruses replicate in infected cells, for instance, how they use entry receptors or exploit host cell trafficking pathways. These gaps in our knowledge are due, in part, to the difficulty of directly observing viruses in living cells. In recent years, advances in light microscopy, including super-resolution microscopy and single-molecule imaging, have enabled many viral replication steps to be visualised dynamically in living cells. In particular, the ability to track single virions and their components, in real time, now allows specific pathways to be interrogated, providing new insights to various aspects of the virus-host cell interaction. In this review, we discuss how state-of-the-art imaging technologies, notably quantitative live-cell and super-resolution microscopy, are providing new nanoscale and molecular insights into influenza virus replication and revealing new opportunities for developing antiviral strategies.


Asunto(s)
Gripe Humana/virología , Microscopía/métodos , Orthomyxoviridae/fisiología , Animales , Humanos , Microscopía/instrumentación , Orthomyxoviridae/genética , Análisis Espacio-Temporal , Replicación Viral
19.
BMC Infect Dis ; 21(1): 52, 2021 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-33430793

RESUMEN

BACKGROUND: Workplace absenteeism increases significantly during influenza epidemics. Sick leave records may facilitate more timely detection of influenza outbreaks, as trends in increased sick leave may precede alerts issued by sentinel surveillance systems by days or weeks. Sick leave data have not been comprehensively evaluated in comparison to traditional surveillance methods. The aim of this paper is to study the performance and the feasibility of using a detection system based on sick leave data to detect influenza outbreaks. METHODS: Sick leave records were extracted from private French health insurance data, covering on average 209,932 companies per year across a wide range of sizes and sectors. We used linear regression to estimate the weekly number of new sick leave spells between 2016 and 2017 in 12 French regions, adjusting for trend, seasonality and worker leaves on historical data from 2010 to 2015. Outbreaks were detected using a 95%-prediction interval. This method was compared to results from the French Sentinelles network, a gold-standard primary care surveillance system currently in place. RESULTS: Using sick leave data, we detected 92% of reported influenza outbreaks between 2016 and 2017, on average 5.88 weeks prior to outbreak peaks. Compared to the existing Sentinelles model, our method had high sensitivity (89%) and positive predictive value (86%), and detected outbreaks on average 2.5 weeks earlier. CONCLUSION: Sick leave surveillance could be a sensitive, specific and timely tool for detection of influenza outbreaks.


Asunto(s)
Absentismo , Epidemias , Gripe Humana/epidemiología , Vigilancia en Salud Pública/métodos , Vigilancia de Guardia , Ausencia por Enfermedad , Francia/epidemiología , Humanos , Incidencia , Gripe Humana/virología , Seguro de Salud , Persona de Mediana Edad , Modelos Estadísticos , Estudios Retrospectivos , Sensibilidad y Especificidad , Lugar de Trabajo
20.
BMC Infect Dis ; 21(1): 68, 2021 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-33441085

RESUMEN

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus that was first discovered in December 2019 in Wuhan, China. With the growing numbers of community spread cases worldwide, the World Health Organization (WHO) declared the COVID-19 outbreak as a pandemic on March 11, 2020. Like influenza viruses, SARS-CoV-2 is thought to be mainly transmitted by droplets and direct contact, and COVID-19 has a similar disease presentation to influenza. Here we present a case of influenza A and COVID-19 co-infection in a 60-year-old man with end-stage renal disease (ESRD) on hemodialysis. CASE PRESENTATION: A 60-year-old man with ESRD on hemodialysis presented for worsening cough, shortness of breath, and diarrhea. The patient first developed a mild fever (37.8 °C) during hemodialysis 3 days prior to presentation and has been experiencing worsening flu-like symptoms, including fever of up to 38.6 °C, non-productive cough, generalized abdominal pain, nausea, vomiting, and liquid green diarrhea. He lives alone at home with no known sick contacts and denies any recent travel or visits to healthcare facilities other than the local dialysis center. Rapid flu test was positive for influenza A. Procalcitonin was elevated at 5.21 ng/mL with a normal white blood cell (WBC) count. Computed tomography (CT) chest demonstrated multifocal areas of consolidation and extensive mediastinal and hilar adenopathy concerning for pneumonia. He was admitted to the biocontainment unit of Nebraska Medicine for concerns of possible COVID-19 and was started on oseltamivir for influenza and vancomycin/cefepime for the probable bacterial cause of his pneumonia and diarrhea. Gastrointestinal (GI) pathogen panel and Clostridioides difficile toxin assay were negative. On the second day of admission, initial nasopharyngeal swab came back positive for SARS-CoV-2 by real-time reverse-transcriptase polymerase chain reaction (RT-PCR). The patient received supportive care and resumed bedside hemodialysis in strict isolation, and eventually fully recovered from COVID-19. CONCLUSIONS: We presented a case of co-infection of influenza and SARS-CoV-2 in a hemodialysis patient. The possibility of SARS-CoV-2 co-infection should not be overlooked even when other viruses including influenza can explain the clinical symptoms, especially in high-risk patients.


Asunto(s)
/diagnóstico , Gripe Humana/diagnóstico , /diagnóstico por imagen , Coinfección/diagnóstico , Coinfección/diagnóstico por imagen , Coinfección/virología , Hospitalización , Humanos , Virus de la Influenza A/genética , Virus de la Influenza A/aislamiento & purificación , Virus de la Influenza A/fisiología , Gripe Humana/diagnóstico por imagen , Gripe Humana/virología , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Pandemias , Diálisis Renal , /aislamiento & purificación , Tomografía Computarizada por Rayos X
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