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1.
Artigo em Inglês | MEDLINE | ID: mdl-34464491

RESUMO

We report a simple and rapid saliva-based SARS-CoV-2 antigen test that utilizes a newly developed dimeric DNA aptamer, denoted as DSA1N5, that specifically recognizes the spike proteins of the wildtype virus and its Alpha and Delta variants with dissociation constants of 120, 290 and 480 pM, respectively, and binds pseudotyped lentiviruses expressing the wildtype and alpha trimeric spike proteins with affinity constants of 2.1 pM and 2.3 pM, respectively. To develop a highly sensitive test, DSA1N5 was immobilized onto gold electrodes to produce an electrochemical impedance sensor, which was capable of detecting 1000 viral particles per mL in 1:1 diluted saliva in under 10 min without any further sample processing. Evaluation of 36 positive and 37 negative patient saliva samples produced a clinical sensitivity of 80.5 % and specificity of 100 % and the sensor could detect the wildtype virus as well as the Alpha and Delta variants in the patient samples, which is the first reported rapid test that can detect any emerging variant of SARS-CoV-2.

2.
Nucleic Acids Res ; 49(13): 7267-7279, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34232998

RESUMO

We performed in vitro selection experiments to identify DNA aptamers for the S1 subunit of the SARS-CoV-2 spike protein (S1 protein). Using a pool of pre-structured random DNA sequences, we obtained over 100 candidate aptamers after 13 cycles of enrichment under progressively more stringent selection pressure. The top 10 sequences all exhibited strong binding to the S1 protein. Two aptamers, named MSA1 (Kd = 1.8 nM) and MSA5 (Kd = 2.7 nM), were assessed for binding to the heat-treated S1 protein, untreated S1 protein spiked into 50% human saliva and the trimeric spike protein of both the wildtype and the B.1.1.7 variant, demonstrating comparable affinities in all cases. MSA1 and MSA5 also recognized the pseudotyped lentivirus of SARS-CoV-2 with respective Kd values of 22.7 pM and 11.8 pM. Secondary structure prediction and sequence truncation experiments revealed that both MSA1 and MSA5 adopted a hairpin structure, which was the motif pre-designed into the original library. A colorimetric sandwich assay was developed using MSA1 as both the recognition element and detection element, which was capable of detecting the pseudotyped lentivirus in 50% saliva with a limit of detection of 400 fM, confirming the potential of these aptamers as diagnostic tools for COVID-19 detection.


Assuntos
Aptâmeros de Nucleotídeos , COVID-19/virologia , Biblioteca Gênica , Mutação , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/genética , Pareamento de Bases , Sequência de Bases , COVID-19/diagnóstico , Colorimetria/métodos , Humanos , Conformação de Ácido Nucleico , Técnica de Seleção de Aptâmeros
3.
Proc Natl Acad Sci U S A ; 118(27)2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34183391

RESUMO

IgA is the second most abundant antibody present in circulation and is enriched at mucosal surfaces. As such, IgA plays a key role in protection against a variety of mucosal pathogens including viruses. In addition to neutralizing viruses directly, IgA can also stimulate Fc-dependent effector functions via engagement of Fc alpha receptors (Fc-αRI) expressed on the surface of certain immune effector cells. Neutrophils are the most abundant leukocyte, express Fc-αRI, and are often the first to respond to sites of injury and infection. Here, we describe a function for IgA-virus immune complexes (ICs) during viral infections. We show that IgA-virus ICs potentiate NETosis-the programmed cell-death pathway through which neutrophils release neutrophil extracellular traps (NETs). Mechanistically, IgA-virus ICs potentiated a suicidal NETosis pathway via engagement of Fc-αRI on neutrophils through a toll-like receptor-independent, NADPH oxidase complex-dependent pathway. NETs also were capable of trapping and inactivating viruses, consistent with an antiviral function.


Assuntos
Armadilhas Extracelulares/imunologia , Imunoglobulina A/imunologia , Neutrófilos/imunologia , Viroses/imunologia , Complexo Antígeno-Anticorpo/imunologia , Antígenos CD/metabolismo , Armadilhas Extracelulares/virologia , Humanos , Influenzavirus A/imunologia , NADPH Oxidases/metabolismo , Neutrófilos/patologia , Neutrófilos/virologia , Receptores Fc/metabolismo , SARS-CoV-2/imunologia , Transdução de Sinais , Vírion
4.
Mucosal Immunol ; 14(5): 1067-1076, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34108594

RESUMO

The upper respiratory tract is highly exposed to airborne pathogens and serves as an important inductive site for protective antibody responses, including mucosal IgA and systemic IgG. However, it is currently unknown to what extent inhaled environmental toxins, such as a cigarette smoke, affect the ability to induce antibody-mediated immunity at this site. Using a murine model of intranasal lipopolysaccharide and ovalbumin (LPS/OVA) immunization, we show that cigarette smoke exposure compromises the induction of antigen-specific IgA in the upper airways and systemic circulation. Deficits in OVA-IgA were observed in conjunction with a reduced accumulation of OVA-specific IgA antibody-secreting cells (ASCs) in the nasal mucosa, inductive tissues (NALT, cervical lymph nodes, spleen) and the blood. Nasal OVA-IgA from smoke-exposed mice also demonstrated reduced avidity during the acute post-immunization period in association with an enhanced mutational burden in the cognate nasal Igha repertoire. Mechanistically, smoke exposure attenuated the ability of the nasal mucosa to upregulate VCAM-1 and pIgR, suggesting that cigarette smoke may inhibit both nasal ASC homing and IgA transepithelial transport. Overall, these findings demonstrate the immunosuppressive nature of tobacco smoke and illustrate the diversity of mechanisms through which this noxious stimulus can interfere with IgA-mediated immunity in the upper airways.

5.
iScience ; : 102477, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33937724

RESUMO

Type I interferons (IFNs) are our first line of defence against virus infection. Recent studies have suggested the ability of SARS-CoV-2 proteins to inhibit IFN responses. Emerging data also suggest that timing and extent of IFN production is associated with manifestation of COVID-19 severity. In spite of progress in understanding how SARS-CoV-2 activates antiviral responses, mechanistic studies into wildtype SARS-CoV-2-mediated induction and inhibition of human type I IFN responses are scarce. Here we demonstrate that SARS-CoV-2 infection induces a type I IFN response in vitro and in moderate cases of COVID-19. In vitro stimulation of type I IFN expression and signaling in human airway epithelial cells is associated with activation of canonical transcriptions factors, and SARS-CoV-2 is unable to inhibit exogenous induction of these responses. Furthermore, we show that physiological levels of IFNα detected in patients with moderate COVID-19 is sufficient to suppress SARS-CoV-2 replication in human airway cells.

6.
Proc Natl Acad Sci U S A ; 118(22)2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34050027

RESUMO

Recombinant influenza virus vaccines based on hemagglutinin (HA) hold the potential to accelerate production timelines and improve efficacy relative to traditional egg-based platforms. Here, we assess a vaccine adjuvant system comprised of immunogenic liposomes that spontaneously convert soluble antigens into a particle format, displayed on the bilayer surface. When trimeric H3 HA was presented on liposomes, antigen delivery to macrophages was improved in vitro, and strong functional antibody responses were induced following intramuscular immunization of mice. Protection was conferred against challenge with a heterologous strain of H3N2 virus, and naive mice were also protected following passive serum transfer. When admixed with the particle-forming liposomes, immunization reduced viral infection severity at vaccine doses as low as 2 ng HA, highlighting dose-sparing potential. In ferrets, immunization induced neutralizing antibodies that reduced the upper respiratory viral load upon challenge with a more modern, heterologous H3N2 viral strain. To demonstrate the flexibility and modular nature of the liposome system, 10 recombinant surface antigens representing distinct influenza virus strains were bound simultaneously to generate a highly multivalent protein particle that with 5 ng individual antigen dosing induced antibodies in mice that specifically recognized the constituent immunogens and conferred protection against heterologous H5N1 influenza virus challenge. Taken together, these results show that stable presentation of recombinant HA on immunogenic liposome surfaces in an arrayed fashion enhances functional immune responses and warrants further attention for the development of broadly protective influenza virus vaccines.

7.
Viruses ; 13(4)2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33923828

RESUMO

Coronavirus Disease 2019 (COVID-19) is a global pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While detection of SARS-CoV-2 by polymerase chain reaction with reverse transcription (RT-PCR) is currently used to diagnose acute COVID-19 infection, serological assays are needed to study the humoral immune response to SARS-CoV-2. Anti-SARS-CoV-2 immunoglobulin (Ig)G/A/M antibodies against spike (S) protein and its receptor-binding domain (RBD) were characterized in recovered subjects who were RT-PCR-positive (n = 153) and RT-PCR-negative (n = 55) using an enzyme-linked immunosorbent assay (ELISA). These antibodies were also further assessed for their ability to neutralize live SARS-CoV-2 virus. Anti-SARS-CoV-2 antibodies were detected in 90.9% of resolved subjects up to 180 days post-symptom onset. Anti-S protein and anti-RBD IgG titers correlated (r = 0.5157 and r = 0.6010, respectively) with viral neutralization. Of the RT-PCR-positive subjects, 22 (14.3%) did not have anti-SARS-CoV-2 antibodies; and of those, 17 had RT-PCR cycle threshold (Ct) values > 27. These high Ct values raise the possibility that these indeterminate results are from individuals who were not infected or had mild infection that failed to elicit an antibody response. This study highlights the importance of serological surveys to determine population-level immunity based on infection numbers as determined by RT-PCR.


Assuntos
Anticorpos Antivirais/imunologia , COVID-19/imunologia , SARS-CoV-2/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/epidemiologia , Teste de Ácido Nucleico para COVID-19 , Teste Sorológico para COVID-19 , Feminino , Humanos , Isotipos de Imunoglobulinas/sangue , Isotipos de Imunoglobulinas/imunologia , Masculino , Pessoa de Meia-Idade , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto Jovem
8.
Biochemistry ; 60(19): 1447-1458, 2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-33930269

RESUMO

Antibody recruiting molecules (ARMs) represent an important class of "proximity-inducing" chemical tools with therapeutic potential. ARMs function by simultaneously binding to a hapten-specific serum antibody (Ab) (e.g., anti-dinitrophenyl (DNP)) and a cancer cell surface protein, enforcing their proximity. ARM anticancer efficacy depends on the formation of ARM:Ab complexes on the cancer cell surface, which activate immune cell recognition and elimination of the cancer cell. Problematically, ARM function in human patients may be limited by conditions that drive the dissociation of ARM:Ab complexes, namely, intrinsically low binding affinity and/or low concentrations of anti-hapten antibodies in human serum. To address this potential limitation, we previously developed a covalent ARM (cARM) chemical tool that eliminates the ARM:antibody equilibrium through a covalent linkage. In the current study, we set out to determine to what extent maximizing the stability of ARM:antibody complexes via cARMs enhances target immune recognition. We observe cARMs significantly increase target immune recognition relative to ARMs across a range of therapeutically relevant antibody concentrations. These results demonstrate that ARM therapeutic function can be dramatically enhanced by increasing the kinetic stability of ARM:antibody complexes localized on cancer cells. Our findings suggest that a) high titres/concentrations of target antibody in human serum are not neccessary and b) saturative antibody recruitment to cancer cells not sufficient, to achieve maximal ARM therapeutic function.

9.
Mol Pharm ; 18(2): 576-592, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32787280

RESUMO

Influenza viruses cause seasonal epidemics and represent a pandemic risk. With current vaccine methods struggling to protect populations against emerging strains, there is a demand for a next-generation flu vaccine capable of providing broad protection. Recombinant biotechnology, combined with nanomedicine techniques, could address this demand by increasing immunogenicity and directing immune responses toward conserved antigenic targets on the virus. Various nanoparticle candidates have been tested for use in vaccines, including virus-like particles, protein and carbohydrate nanoconstructs, antigen-carrying lipid particles, and synthetic and inorganic particles modified for antigen presentation. These methods have yielded some promising results, including protection in animal models against antigenically distinct influenza strains, production of antibodies with broad reactivity, and activation of potent T cell responses. Based on the evidence of current research, it is feasible that the next generation of influenza vaccines will combine recombinant antigens with nanoparticle carriers.

10.
Cell Rep Med ; 1(7): 100126, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33015650

RESUMO

SARS-CoV-2 is responsible for the coronavirus disease 2019 (COVID-19) pandemic, infecting millions of people and causing hundreds of thousands of deaths. The Spike glycoproteins of SARS-CoV-2 mediate viral entry and are the main targets for neutralizing antibodies. Understanding the antibody response directed against SARS-CoV-2 is crucial for the development of vaccine, therapeutic, and public health interventions. Here, we perform a cross-sectional study on 106 SARS-CoV-2-infected individuals to evaluate humoral responses against SARS-CoV-2 Spike. Most infected individuals elicit anti-Spike antibodies within 2 weeks of the onset of symptoms. The levels of receptor binding domain (RBD)-specific immunoglobulin G (IgG) persist over time, and the levels of anti-RBD IgM decrease after symptom resolution. Although most individuals develop neutralizing antibodies within 2 weeks of infection, the level of neutralizing activity is significantly decreased over time. Our results highlight the importance of studying the persistence of neutralizing activity upon natural SARS-CoV-2 infection.

11.
J Vet Intern Med ; 34(6): 2468-2477, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33026128

RESUMO

BACKGROUND: Proteinuria has been associated with progression of renal disease and increased morbidity and mortality in dogs and people. In people, proteinuria also has been associated with hypovitaminosis D. Little is known about the relationship between vitamin D metabolism and proteinuria in dogs. OBJECTIVES: To further elucidate vitamin D status in dogs with protein-losing nephropathy (PLN) and minimal to no azotemia. We hypothesized that vitamin D metabolites would be lower in dogs with PLN compared to healthy dogs. ANIMALS: Twenty-three client-owned adult dogs with PLN and 10 healthy control dogs. METHODS: Serum 25-hydroxyvitamin D (25[OH]D), 1,25-dihydroxyvitamin D (1,25[OH]2 D), 24,25-dihydroxyvitamin D (24,25[OH]2 D), serum vitamin D binding protein (VDBP), and urine 25(OH)D concentrations were measured. RESULTS: Compared to healthy dogs, dogs with PLN had lower concentrations of all vitamin D metabolites (P < .01). Correlations (rho; 95% confidence interval [CI]) in dogs with PLN are reported. Serum 25(OH)D and 24,25(OH)2 D concentrations were positively correlated with albumin (r = 0.47; 0.07-0.74), and 24,25(OH)2 D was negatively correlated with urine protein-to-creatinine ratio (UPC; r = -0.54; -0.78 to -0.16). Urine 25(OH)D-to-creatinine ratio was negatively correlated with serum albumin concentration (r = -0.77; -0.91 to -0.50) and positively correlated with UPC (r = 0.79; 0.53-0.91). Serum VDBP concentration was positively correlated with serum albumin concentration (r = 0.53; 0.05-0.81). CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with PLN have decreased serum concentrations of vitamin D metabolites. Urine 25(OH)D-to-creatinine ratio and UPC are correlated in PLN dogs. Future studies are needed to assess additional management strategies for dogs with PLN.


Assuntos
Doenças do Cão , Deficiência de Vitamina D , Animais , Cães , Proteinúria/veterinária , Vitamina D , Deficiência de Vitamina D/veterinária , Proteína de Ligação a Vitamina D
12.
Nat Rev Immunol ; 20(10): 615-632, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32887954

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the most formidable challenge to humanity in a century. It is widely believed that prepandemic normalcy will never return until a safe and effective vaccine strategy becomes available and a global vaccination programme is implemented successfully. Here, we discuss the immunological principles that need to be taken into consideration in the development of COVID-19 vaccine strategies. On the basis of these principles, we examine the current COVID-19 vaccine candidates, their strengths and potential shortfalls, and make inferences about their chances of success. Finally, we discuss the scientific and practical challenges that will be faced in the process of developing a successful vaccine and the ways in which COVID-19 vaccine strategies may evolve over the next few years.


Assuntos
Anticorpos Antivirais/biossíntese , Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/prevenção & controle , Vacinas Virais/imunologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/patogenicidade , COVID-19 , Vacinas contra COVID-19 , Ensaios Clínicos como Assunto , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Vetores Genéticos/química , Vetores Genéticos/imunologia , Humanos , Imunidade Coletiva/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Esquemas de Imunização , Imunogenicidade da Vacina , Segurança do Paciente , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , SARS-CoV-2 , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/virologia , Vacinas Atenuadas , Vacinas de DNA , Vacinas de Subunidades , Vacinas de Partículas Semelhantes a Vírus , Vacinas Virais/administração & dosagem , Vacinas Virais/biossíntese
13.
J Gen Virol ; 101(12): 1251-1260, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32902372

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently emerged to cause widespread infections in humans. SARS-CoV-2 infections have been reported in the Kingdom of Saudi Arabia, where Middle East respiratory syndrome coronavirus (MERS-CoV) causes seasonal outbreaks with a case fatality rate of ~37 %. Here we show that there exists a theoretical possibility of future recombination events between SARS-CoV-2 and MERS-CoV RNA. Through computational analyses, we have identified homologous genomic regions within the ORF1ab and S genes that could facilitate recombination, and have analysed co-expression patterns of the cellular receptors for SARS-CoV-2 and MERS-CoV, ACE2 and DPP4, respectively, to identify human anatomical sites that could facilitate co-infection. Furthermore, we have investigated the likely susceptibility of various animal species to MERS-CoV and SARS-CoV-2 infection by comparing known virus spike protein-receptor interacting residues. In conclusion, we suggest that a recombination between SARS-CoV-2 and MERS-CoV RNA is possible and urge public health laboratories in high-risk areas to develop diagnostic capability for the detection of recombined coronaviruses in patient samples.


Assuntos
Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Vírus Reordenados , SARS-CoV-2/genética , Animais , Sequência de Bases , Coinfecção , Regulação Viral da Expressão Gênica , Genoma Viral , Especificidade de Hospedeiro , Humanos , Modelos Moleculares , Filogenia , Conformação Proteica , Receptores de Superfície Celular , Recombinação Genética , Proteínas Virais/química , Proteínas Virais/genética , Proteínas Virais/metabolismo
14.
Eur Respir J ; 56(3)2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32675206

RESUMO

In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged, causing the coronavirus disease 2019 (COVID-19) pandemic. SARS-CoV, the agent responsible for the 2003 SARS outbreak, utilises angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) host molecules for viral entry. ACE2 and TMPRSS2 have recently been implicated in SARS-CoV-2 viral infection. Additional host molecules including ADAM17, cathepsin L, CD147 and GRP78 may also function as receptors for SARS-CoV-2.To determine the expression and in situ localisation of candidate SARS-CoV-2 receptors in the respiratory mucosa, we analysed gene expression datasets from airway epithelial cells of 515 healthy subjects, gene promoter activity analysis using the FANTOM5 dataset containing 120 distinct sample types, single cell RNA sequencing (scRNAseq) of 10 healthy subjects, proteomic datasets, immunoblots on multiple airway epithelial cell types, and immunohistochemistry on 98 human lung samples.We demonstrate absent to low ACE2 promoter activity in a variety of lung epithelial cell samples and low ACE2 gene expression in both microarray and scRNAseq datasets of epithelial cell populations. Consistent with gene expression, rare ACE2 protein expression was observed in the airway epithelium and alveoli of human lung, confirmed with proteomics. We present confirmatory evidence for the presence of TMPRSS2, CD147 and GRP78 protein in vitro in airway epithelial cells and confirm broad in situ protein expression of CD147 and GRP78 in the respiratory mucosa.Collectively, our data suggest the presence of a mechanism dynamically regulating ACE2 expression in human lung, perhaps in periods of SARS-CoV-2 infection, and also suggest that alternative receptors for SARS-CoV-2 exist to facilitate initial host cell infection.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus , Pandemias , Peptidil Dipeptidase A , Pneumonia Viral , Serina Endopeptidases , Enzima de Conversão de Angiotensina 2 , COVID-19 , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Expressão Gênica , Perfilação da Expressão Gênica/métodos , Humanos , Pulmão/metabolismo , Pulmão/virologia , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia , Receptores Virais/classificação , Receptores Virais/genética , Receptores Virais/metabolismo , Mucosa Respiratória/metabolismo , Mucosa Respiratória/virologia , SARS-CoV-2 , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismo , Internalização do Vírus
15.
bioRxiv ; 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32577637

RESUMO

The SARS-CoV-2 virus is responsible for the current worldwide coronavirus disease 2019 (COVID-19) pandemic, infecting millions of people and causing hundreds of thousands of deaths. The Spike glycoprotein of SARS-CoV-2 mediates viral entry and is the main target for neutralizing antibodies. Understanding the antibody response directed against SARS-CoV-2 is crucial for the development of vaccine, therapeutic and public health interventions. Here we performed a cross-sectional study on 98 SARS-CoV-2-infected individuals to evaluate humoral responses against the SARS-CoV-2 Spike. The vast majority of infected individuals elicited anti-Spike antibodies within 2 weeks after the onset of symptoms. The levels of receptor-binding domain (RBD)-specific IgG persisted overtime, while the levels of anti-RBD IgM decreased after symptoms resolution. Some of the elicited antibodies cross-reacted with other human coronaviruses in a genus-restrictive manner. While most of individuals developed neutralizing antibodies within the first two weeks of infection, the level of neutralizing activity was significantly decreased over time. Our results highlight the importance of studying the persistence of neutralizing activity upon natural SARS-CoV-2 infection.

16.
Emerg Infect Dis ; 26(9): 2054-2063, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32558639

RESUMO

Since its emergence in Wuhan, China, in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected ≈6 million persons worldwide. As SARS-CoV-2 spreads across the planet, we explored the range of human cells that can be infected by this virus. We isolated SARS-CoV-2 from 2 infected patients in Toronto, Canada; determined the genomic sequences; and identified single-nucleotide changes in representative populations of our virus stocks. We also tested a wide range of human immune cells for productive infection with SARS-CoV-2. We confirm that human primary peripheral blood mononuclear cells are not permissive for SARS-CoV-2. As SARS-CoV-2 continues to spread globally, it is essential to monitor single-nucleotide polymorphisms in the virus and to continue to isolate circulating viruses to determine viral genotype and phenotype by using in vitro and in vivo infection models.


Assuntos
Betacoronavirus , Infecções por Coronavirus/virologia , Leucócitos Mononucleares/virologia , Pneumonia Viral/virologia , Replicação Viral/genética , Betacoronavirus/genética , Betacoronavirus/isolamento & purificação , Betacoronavirus/fisiologia , COVID-19 , DNA Viral/genética , DNA Viral/isolamento & purificação , Genótipo , Humanos , Cinética , Pandemias , Polimorfismo de Nucleotídeo Único , SARS-CoV-2 , Sequenciamento Completo do Genoma
17.
Trends Microbiol ; 28(9): 703-706, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32409145

RESUMO

MHC class II (MHCII) has recently been identified as a cellular receptor for bat influenza viruses. Here, we discuss the possible implications of viral exploitation of this critical host defense molecule and highlight the need for more intense study of bat-influenza virus interactions.


Assuntos
Quirópteros/virologia , Antígenos de Histocompatibilidade Classe II/imunologia , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/transmissão , Orthomyxoviridae/imunologia , Animais , Interações entre Hospedeiro e Microrganismos , Humanos , Vírus da Influenza A/imunologia , Influenza Humana/imunologia , Influenza Humana/transmissão , Influenza Humana/virologia , Infecções por Orthomyxoviridae/virologia , Linfócitos T/imunologia , Tropismo Viral , Zoonoses/virologia
18.
Clin Infect Dis ; 71(7): e195-e198, 2020 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-31985006

RESUMO

When H3N2 replaced H1N1 as the dominant influenza A subtype during the 2018-2019 season, the pattern of age-specific incidence shifted due to the lingering effects of antigenic imprinting. The characteristic shape that imprinting leaves on influenza susceptibility could foster important advances in understanding and predicting the epidemiology of influenza.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Fatores Etários , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Humanos , Incidência , Vírus da Influenza A Subtipo H3N2 , Influenza Humana/epidemiologia , Estações do Ano
20.
Demography ; 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31659681

RESUMO

First, we use Lexis surfaces based on Serfling models to highlight influenza mortality patterns as well as to identify lingering effects of early-life exposure to specific influenza virus subtypes (e.g., H1N1, H3N2).

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