Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 136
Filtrar
1.
Sci Rep ; 14(1): 11823, 2024 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-38783052

RESUMO

Our previous findings indicated that many respiratory syncytial virus (RSV) isolates are unstable at 4 °C compared to 20 °C. Some of the strains completely lose infectivity after 24 h at 4 °C. This study analyzed the inactivation process at 4 °C using a representative strain, RSV/Sendai/851/13. After 24 h of storage at 4 °C, the virus was completely inactivated but retained its ability to attach to and to be taken into host cells. It suggested a reduced fusion ability between the viral and cellular membranes. During storage at 4 °C, the RSV fusion (F) protein underwent a conformational change and was no longer recognized by pre-fusion form-specific antibodies. When the RSV/Sendai/851/13 strain was passaged at 4 °C, a variant with an amino acid substitution, I148T, in the F protein fusion peptide was selected. Also, an amino acid change in G protein demonstrating stability at low temperatures was obtained. These results show that the inactivation of RSV at 4 °C is due to the loss of membrane fusion activity in the F protein, which cannot maintain its pre-fusion state at 4 °C.


Assuntos
Temperatura Baixa , Vírus Sincicial Respiratório Humano , Proteínas Virais de Fusão , Inativação de Vírus , Proteínas Virais de Fusão/metabolismo , Proteínas Virais de Fusão/genética , Proteínas Virais de Fusão/química , Humanos , Vírus Sincicial Respiratório Humano/fisiologia , Animais , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sinciciais Respiratórios
3.
J Prosthodont Res ; 68(1): 85-91, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36823102

RESUMO

PURPOSE: The hazards of aerosols generated during dental treatments are poorly understood. This study aimed to establish visualization methods, discover conditions for droplets/aerosols generated in simulating dental treatments and identify the conditions for effective suction methods. METHODS: The spreading area was evaluated via image analysis of the droplets/aerosols generated by a dental air turbine on a mannequin using a light emitting diode (LED) light source and high-speed camera. The effects of different bur types and treatment sites, reduction effect of intra-oral suction (IOS) and extra-oral suction (EOS) devices, and effect of EOS installation conditions were evaluated. RESULTS: Regarding the bur types, a bud-shaped bur on the air turbine generated the most droplets/aerosols compared with round-shaped, round end-tapered, or needle-tapered burs. Regarding the treatment site, the area of droplets/aerosols produced by an air turbine from the palatal plane of the anterior maxillary teeth was significantly higher. The generated droplet/aerosol area was reduced by 92.1% by using IOS alone and 97.8% by combining IOS and EOS. EOS most effectively aspirated droplets/aerosols when placed close (10 cm) to the mouth in the vertical direction (0°). CONCLUSIONS: The droplets/aerosols generated by an air turbine could be visualized using an LED light and a high-speed camera in simulating dental treatments. The bur shape and position of the dental air turbine considerably influenced droplet/aerosol diffusion. The combined use of IOS and EOS at a proper position (close and perpendicular to the mouth) facilitated effective diffusion prevention to protect the dental-care environment.


Assuntos
Assistência Odontológica , Boca , Humanos , Sucção , Aerossóis
4.
Viruses ; 15(6)2023 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-37376555

RESUMO

Rapid molecular testing for severe acute respiratory coronavirus 2 (SARS-CoV-2) variants may contribute to the development of public health measures, particularly in resource-limited areas. Reverse transcription recombinase polymerase amplification using a lateral flow assay (RT-RPA-LF) allows rapid RNA detection without thermal cyclers. In this study, we developed two assays to detect SARS-CoV-2 nucleocapsid (N) gene and Omicron BA.1 spike (S) gene-specific deletion-insertion mutations (del211/ins214). Both tests had a detection limit of 10 copies/µL in vitro and the detection time was approximately 35 min from incubation to detection. The sensitivities of SARS-CoV-2 (N) RT-RPA-LF by viral load categories were 100% for clinical samples with high (>9015.7 copies/µL, cycle quantification (Cq): < 25) and moderate (385.5-9015.7 copies/µL, Cq: 25-29.9) viral load, 83.3% for low (16.5-385.5 copies/µL, Cq: 30-34.9), and 14.3% for very low (<16.5 copies/µL, Cq: 35-40). The sensitivities of the Omicron BA.1 (S) RT-RPA-LF were 94.9%, 78%, 23.8%, and 0%, respectively, and the specificity against non-BA.1 SARS-CoV-2-positive samples was 96%. The assays seemed more sensitive than rapid antigen detection in moderate viral load samples. Although implementation in resource-limited settings requires additional improvements, deletion-insertion mutations were successfully detected by the RT-RPA-LF technique.


Assuntos
COVID-19 , Transcrição Reversa , Humanos , Recombinases/genética , RNA Viral/genética , SARS-CoV-2/genética , Sensibilidade e Especificidade , Mutagênese Insercional , COVID-19/diagnóstico , COVID-19/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , Nucleotidiltransferases/genética
5.
J Clin Virol ; 162: 105429, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37031609

RESUMO

BACKGROUND: Influenza C virus is a pathogen that causes acute respiratory illness in children. The clinical information about this virus is limited because of the small number of isolated viruses compared to influenza A or B viruses. METHODS: A total of 60 influenza C viruses were isolated by clinical tests using cell culture methods conducted in one hospital and one clinic during the 15 years from 2006 to 2020. These 60 cases were retrospectively analyzed by comparing outpatients and inpatients. Moreover, isolated viruses were analyzed for genomic changes during the study period. RESULTS: All were younger than 7 years, and 73% of inpatients (19 out of 26) were under 2 years of age. A significant difference was found in the frequency of pneumonia, accounting for 45% and 4% of inpatients and outpatients, respectively. Most of the viruses isolated from 2006 to 2012 belonged to the S/A sublineage of the C/Sao Paulo lineage, but three sublineage viruses, including the S/A sublineage with K190N mutation, S/V sublineage, and C/Kanagawa lineage, have cocirculated since 2014. Moreover, S/A sublineage viruses were undergoing reassortment since 2014, suggesting significant changes in the virus, both antigenically and genetically. Of the 10 strains from patients with pneumonia, 7 were in the S/A sublineage, which had circulated from 2006 to 2012. CONCLUSION: Infants under 2 years of age were more likely to be hospitalized with pneumonia. The genomic changes that occurred in 2014 were suggested to affect the ability of the virus to spread.


Assuntos
Gammainfluenzavirus , Influenza Humana , Lactente , Criança , Humanos , Gammainfluenzavirus/genética , Pacientes Ambulatoriais , Pacientes Internados , Japão/epidemiologia , Estudos Retrospectivos , Brasil , Influenza Humana/epidemiologia
7.
Viruses ; 15(1)2023 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-36680284

RESUMO

The emergence and spread of antiviral-resistant influenza viruses are of great concern. To minimize the public health risk, it is important to monitor antiviral susceptibilities of influenza viruses. Analyses of the antiviral susceptibilities of influenza A and B viruses have been conducted globally; however, those of influenza C and D viruses are limited. Here, we determined the susceptibilities of influenza C viruses representing all six lineages (C/Taylor, C/Yamagata, C/Sao Paulo, C/Aichi, C/Kanagawa, and C/Mississippi) and influenza D viruses representing four lineages (D/OK, D/660, D/Yama2016, and D/Yama2019) to RNA polymerase inhibitors (baloxavir and favipiravir) by using a focus reduction assay. All viruses tested were susceptible to both drugs. We then performed a genetic analysis to check for amino acid substitutions associated with baloxavir and favipiravir resistance and found that none of the viruses tested possessed these substitutions. Use of the focus reduction assay with the genotypic assay has proven valuable for monitoring the antiviral susceptibilities of influenza C and D viruses as well as influenza A and B viruses. Antiviral susceptibility monitoring of all influenza virus types should continue in order to assess the public health risks posed by these viruses.


Assuntos
Influenza Humana , Orthomyxoviridae , Humanos , Influenza Humana/tratamento farmacológico , Antivirais/farmacologia , Antivirais/uso terapêutico , Brasil , Farmacorresistência Viral/genética
8.
Respir Investig ; 61(2): 270-283, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36543714

RESUMO

Respiratory viruses like rhinovirus, influenza virus, respiratory syncytial virus, and coronavirus cause several respiratory diseases, such as bronchitis, pneumonia, pulmonary fibrosis, and coronavirus disease 2019, and exacerbate bronchial asthma, chronic obstructive pulmonary disease, bronchiectasis, and diffuse panbronchiolitis. The production of inflammatory mediators and mucin and the accumulation of inflammatory cells have been reported in patients with viral infection-induced respiratory diseases. Interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor-α, granulocyte-macrophage colony-stimulating factor, and regulated on activation normal T-cell expressed and secreted are produced in the cells, including human airway and alveolar epithelial cells, partly through the activation of toll-like receptors, nuclear factor kappa B and p44/42 mitogen-activated protein kinase. These mediators are associated with the development of viral infection-induced respiratory diseases through the induction of inflammation and injury in the airway and lung, airway remodeling and hyperresponsiveness, and mucus secretion. Medications used to treat respiratory diseases, including corticosteroids, long-acting ß2-agonists, long-acting muscarinic antagonists, mucolytic agents, antiviral drugs for severe acute respiratory syndrome coronavirus 2 and influenza virus, macrolides, and Kampo medicines, reduce the production of viral infection-induced mediators, including cytokines and mucin, as determined in clinical, in vivo, or in vitro studies. These results suggest that the anti-inflammatory effects of these medications on viral infection-induced respiratory diseases may be associated with clinical benefits, such as improvements in symptoms, quality of life, and mortality rate, and can prevent hospitalization and the exacerbation of chronic obstructive pulmonary disease, bronchial asthma, bronchiectasis, and diffuse panbronchiolitis.


Assuntos
Asma , Bronquiectasia , COVID-19 , Doença Pulmonar Obstrutiva Crônica , Viroses , Humanos , Qualidade de Vida , Asma/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Viroses/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Mucinas/uso terapêutico
9.
Life Sci Alliance ; 6(1)2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36344085

RESUMO

The efficacy of the current influenza vaccines is frequently reduced because of antigenic drift, a trade-off of developing improved vaccines with broad cross-protective activity against influenza A viruses. In this study, we have successfully constructed a chimeric cytokine (CC) comprising the M2 protein, influenza A neuraminidase stalk, and interleukin-12. We produced virus-like particles (VLPs) containing CC and influenza hemagglutinin (HA) proteins using a baculovirus system in Eri silkworm pupae. The protective efficacy of the CCHA-VLP vaccine was evaluated in mice. The CCFkH5HA-VLP vaccine increased the survival rates of BALB/c mice, infected with a lethal dose of PRH1 and HKH5 viruses, to 80% and 100%, respectively. The results suggested that CCHA-VLP successfully induced potent cross-reactive protective immunity against infection with homologous and heterologous subtypes of the influenza A virus. This is the first study to design a CC-containing HA-VLP vaccine and validate its protective efficacy.


Assuntos
Vacinas contra Influenza , Influenza Humana , Infecções por Orthomyxoviridae , Vacinas de Partículas Semelhantes a Vírus , Camundongos , Animais , Humanos , Influenza Humana/prevenção & controle , Vacinas de Partículas Semelhantes a Vírus/genética , Citocinas , Infecções por Orthomyxoviridae/prevenção & controle , Anticorpos Antivirais , Hemaglutininas , Camundongos Endogâmicos BALB C
10.
J Clin Virol ; 154: 105238, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35907395

RESUMO

BACKGROUND: To detect human metapneumovirus, tests besides reverse transcription-polymerase chain reaction (RT-PCR) on nasopharyngeal swab specimens are less accessible. Immunochromatography assays are rapid and simple without the need of any special equipment but sometimes are insufficiently sensitive. This study describes the usefulness of immunochromatography assays to detect human metapneumovirus in adult patients with human metapneumovirus-related acute lower respiratory tract infection using sputum specimens. METHODS: This prospective single-center study enrolled adults and adolescents aged ≥16 years with signs and symptoms of an acute respiratory illness who were diagnosed with acute lower respiratory tract infection. The presence of human metapneumovirus infection was confirmed by seroconversion. Immunochromatography assays and real-time RT-PCR were performed to compare the efficacy of nasopharyngeal swab specimens and sputum specimens. Comparative results were obtained via McNemar's test. RESULTS: Overall, 337 patients were recruited in this study; 63 (18.7%) patients were seroconverted. Sputum specimens showed significantly higher positivity rates than nasopharyngeal swab specimens with both immunochromatography assays (p = 0.0008) and real-time RT-PCR (p = 0.014). Among 29 patients with pneumonia who had concordant positive real-time RT-PCR results for both nasopharyngeal swab specimens and sputum specimens, 21 (72.4%) had a higher viral load in the sputum specimens. CONCLUSIONS: Sputum specimens are more useful in detecting human metapneumovirus than nasopharyngeal swab specimens in adult patients with acute lower respiratory tract infection.


Assuntos
Metapneumovirus , Infecções por Paramyxoviridae , Infecções Respiratórias , Adolescente , Adulto , Humanos , Metapneumovirus/genética , Nasofaringe , Infecções por Paramyxoviridae/diagnóstico , Estudos Prospectivos , Infecções Respiratórias/diagnóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e Especificidade , Escarro
11.
Pathogens ; 11(7)2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35889999

RESUMO

The World Health Organization initiated a global surveillance system for respiratory syncytial virus (RSV) in 2015, and the pilot surveillance is ongoing. The real-time RT-PCR RSV assays (Pan-RSV and duplex assays) developed by the United States Centers for Disease Control and Prevention are applied as the standard assays. To introduce these as standard assays in Japan, their practicality was evaluated using 2261 specimens obtained from pediatric inpatients in Japan, which were collected from 2018 to 2021. Although the Pan-RSV and duplex assays had similar analytical sensitivities, they yielded 630 (27.9%) and 786 (34.8%) RSV-positive specimens, respectively (p < 0.001). Although sequencing analysis showed mismatches in the reverse primer used in the Pan-RSV assay, these mismatches did not affect its analytical sensitivity. The analysis of read numbers of RSV isolates from air−liquid interface culture of human bronchial/tracheal epithelial cells showed that the duplex assay had a greater number of reads than did the Pan-RSV assay. Therefore, the duplex assay has superior detection performance compared with the Pan-RSV assay, but the two assays have similar analytical sensitivities.

12.
Microbiol Immunol ; 66(7): 361-370, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35545856

RESUMO

The practical use of cell-based seasonal influenza vaccines is currently being considered in Japan. From the perspective of adventitious virus contamination, we assessed the suitability of NIID-MDCK cells (NIID-MDCK-Cs) as a safe substrate for the isolation of influenza viruses from clinical specimens. We first established a sensitive multiplex real-time PCR system to screen for 27 respiratory viruses and used it on 34 virus samples that were isolated by passaging influenza-positive clinical specimens in NIID-MDCK-Cs. Incidentally, the limit of detection (LOD) of the system was 100 or fewer genome copies per reaction. In addition to influenza viruses, human enterovirus 68 (HEV-D68) genomes were detected in two samples after two or three passages in NIID-MDCK-Cs. To further investigate the susceptibility of NIID-MDCK-Cs to adventitious viruses, eight common respiratory viruses were subjected to passages in NIID-MDCK-Cs. The genome copy numbers of seven viruses other than parainfluenza 3 decreased below the LOD by passage 4. By passaging in NIID-MDCK-Cs, the genome numbers of the input HEV-D68, 1 × 108 copies, declined to 102 at passage 3 and to under the LOD at passage 4, whereas those of the other six viruses were under the LOD by passage 3. These results implied that during the process of isolating influenza viruses with NIID-MDCK-Cs, contaminating viruses other than parainfluenza 3 can be efficiently removed by passages in NIID-MDCK-Cs. NIID-MDCK-Cs could be a safe substrate for isolating influenza viruses that can be used to develop cell-based influenza vaccine candidate viruses.


Assuntos
Vacinas contra Influenza , Influenza Humana , Orthomyxoviridae , Infecções por Paramyxoviridae , Vírus , Animais , Cães , Humanos , Vacinas contra Influenza/genética , Influenza Humana/prevenção & controle , Células Madin Darby de Rim Canino , Desenvolvimento de Vacinas , Cultura de Vírus/métodos
13.
Viruses ; 14(4)2022 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-35458409

RESUMO

Virus isolates are not only useful for diagnosing infections, e.g., respiratory syncytial virus (RSV), but can also facilitate many aspects of practical viral studies such as analyses of antigenicity and the action mechanisms of antivirals, among others. We have been isolating RSV from clinical specimens from patients with respiratory symptoms every year since our first isolation of RSV in 1964, and isolation rates have varied considerably over the years. As collected clinical specimens are conventionally stored in a refrigerator from collection to inoculation into cells, we hypothesized that certain storage conditions or associated factors might account for these differences. Hence, we evaluated the thermal stability of a total of 64 viruses isolated from 1998 to 2018 upon storage at 4 °C and 20 °C for a defined duration. Interestingly, and contrary to our current understanding, 22 strains (34%) showed a greater loss of viability upon short-term storage at 4 °C than at 20 °C. Thirty-seven strains (57%) showed an almost equal loss, and only five strains (8%) were more stable at 4 °C than at 20 °C. This finding warrants reconsideration of the temperature for the temporary storage of clinical samples for RSV isolation.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Humanos , Lactente , Temperatura
14.
Infect Prev Pract ; 4(1): 100193, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34901825

RESUMO

BACKGROUND: Physicians have had to perform numerous extubation procedures during the prolonged coronavirus disease 2019 (COVID 19) pandemic. Future pandemics caused by unknown pathogen may also present a risk of exposure to infectious droplets and aerosols. AIM: This study evaluated the ability of a newly developed aerosol barrier, "Extubation-Aerosol (EA)-Shield" to provide maximum protection from aerosol exposure during extubation via an aerosolised particle count and high-quality visualisation assessments. METHODS: We employed a cough model having parameters similar to humans and used micron oil aerosol as well as titanium dioxide as aerosol tracers. Aerosol barrier techniques employing a face mask (group M) and EA-Shield (group H) were compared. FINDINGS: The primary outcome was the difference in the number of particles contacting the physician's face before and after extubation. The maximum distances of aerosol dispersal after extubation were measured as the secondary outcomes. All aerosolised particles of the two tracers were significantly smaller in group H than in group M (p < 0.05). In addition, the sagittal and axial maximum distances and sagittal areas of aerosol dispersal for 3, 5, and 10 s after extubation were significantly smaller in group H than in group M (p < 0.05). CONCLUSION: This model indicates that EA-Shield could be highly effective in reducing aerosol exposure during extubation. Therefore, we recommend using it as an aerosol barrier when an infectious aerosol risk is suspected.

15.
J Virol ; 95(23): e0151521, 2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-34523967

RESUMO

Although epidemics of hand, foot, and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) have occurred worldwide, the Asia-Pacific region has seen large sporadic outbreaks with many severe neurological cases. This suggests that the virulence of the circulating viruses fluctuates in each epidemic and that HFMD outbreaks with many severe cases occur when highly virulent viruses are circulating predominantly, which has not been experimentally verified. Here, we analyzed 32 clinically isolated strains obtained in Japan from 2002 to 2013, along with 27 Vietnamese strains obtained from 2015 to 2016 that we characterized previously using human SCARB2 transgenic mice. Phylogenetic analysis of the P1 region classified them into five clades belonging to subgenogroup B5 (B5-I to B5-V) and five clades belonging to subgenogroup C4 (C4-I to C4-V) according to the epidemic year and region. Interestingly, clades B5-I and B5-II were very virulent, while clades B5-III, B5-IV, and B5-V were less virulent. Clades C4-II, C4-III, C4-IV, and C4-V were virulent, while clade C4-I was not. The result experimentally showed for the first time that several clades with different virulence levels emerged one after another. The experimental virulence evaluation of circulating viruses using SCARB2 transgenic mice is helpful to assess potential risks of circulating viruses. These results also suggest that a minor nucleotide or amino acid substitution in the EV-A71 genome during circulation causes fluctuations in virulence. The data presented here may increase our understanding of the dynamics of viral virulence during epidemics. IMPORTANCE Outbreaks of hand, foot, and mouth disease (HFMD) with severe enterovirus A71 (EV-A71) cases have occurred repeatedly, mainly in Asia. In severe cases, central nervous system complications can lead to death, making it an infectious disease of importance to public health. An unanswered question about this disease is why outbreaks of HFMD with many severe cases sometimes occur. Here, we collected EV-A71 strains that were prevalent in Japan and Vietnam over the past 20 years and evaluated their virulence in a mouse model of EV-A71 infection. This method clearly revealed that viruses belonging to different clades have different virulence, indicating that the method is powerful to assess the potential risks of the circulating viruses. The results also suggested that factors in the virus genome cause an outbreak with many severe cases and that further studies facilitate the prediction of large epidemics of EV-A71 in the future.


Assuntos
Infecções por Enterovirus/epidemiologia , Infecções por Enterovirus/virologia , Enterovirus/classificação , Enterovirus/genética , Epidemias , Genoma Viral , Filogenia , Animais , Surtos de Doenças , Enterovirus Humano A/genética , Feminino , Doença de Mão, Pé e Boca , Humanos , Japão/epidemiologia , Masculino , Camundongos , Camundongos Transgênicos , Mutação , Vietnã/epidemiologia , Virulência/genética
16.
J Virol ; 95(21): e0129621, 2021 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-34406864

RESUMO

Influenza C virus (ICV) has only one kind of spike protein, the hemagglutinin-esterase (HE) glycoprotein. HE functions similarly to hemagglutinin (HA) and neuraminidase of the influenza A and B viruses (IAV and IBV, respectively). It has a monobasic site, which is cleaved by some host enzymes. The cleavage is essential to activating the virus, but the enzyme or enzymes in the respiratory tract have not been identified. This study investigated whether the host serine proteases, transmembrane protease serine S1 member 2 (TMPRSS2) and human airway trypsin-like protease (HAT), which reportedly cleave HA of IAV/IBV, are involved in HE cleavage. We established TMPRSS2- and HAT-expressing MDCK cells (MDCK-TMPRSS2 and MDCK-HAT). ICV showed multicycle replication with HE cleavage without trypsin in MDCK-TMPRSS2 cells as well as IAV did. The HE cleavage and multicycle replication did not appear in MDCK-HAT cells infected with ICV without trypsin, while HA cleavage and multistep growth of IAV appeared in the cells. Amino acid sequences of the HE cleavage site in 352 ICV strains were completely preserved. Camostat and nafamostat suppressed the growth of ICV and IAV in human nasal surface epithelial (HNE) cells. Therefore, this study revealed that, at least, TMPRSS2 is involved in HE cleavage and suggested that nafamostat could be a candidate for therapeutic drugs for ICV infection. IMPORTANCE Influenza C virus (ICV) is a pathogen that causes acute respiratory illness, mostly in children, but there are no anti-ICV drugs. ICV has only one kind of spike protein, the hemagglutinin-esterase (HE) glycoprotein on the virion surface, which possesses receptor-binding, receptor-destroying, and membrane fusion activities. The HE cleavage is essential for the virus to be activated, but the enzyme or enzymes in the respiratory tract have not been identified. This study revealed that transmembrane protease serine S1 member 2 (TMPRSS2), and not human airway trypsin-like protease (HAT), is involved in HE cleavage. This is a novel study on the host enzymes involved in HE cleavage, and the result suggests that the host enzymes, such as TMPRSS2, may be a target for therapeutic drugs of ICV infection.


Assuntos
Gammainfluenzavirus/enzimologia , Gammainfluenzavirus/metabolismo , Hemaglutininas Virais/metabolismo , Influenza Humana/virologia , Infecções por Orthomyxoviridae/virologia , Serina Endopeptidases/metabolismo , Proteínas Virais de Fusão/metabolismo , Sequência de Aminoácidos , Animais , Antivirais/farmacologia , Benzamidinas/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , Células Cultivadas , Cães , Ésteres/farmacologia , Guanidinas/farmacologia , Interações entre Hospedeiro e Microrganismos , Humanos , Células Madin Darby de Rim Canino , Tripsina/metabolismo , Proteínas Virais/metabolismo
17.
Virus Res ; 304: 198548, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34425162

RESUMO

Rhinovirus species C (RV-C) causes more severe asthma attacks than other rhinovirus species. However, the modulation of RV-C replication by drugs has not been well studied. Primary human nasal epithelial (HNE) cells cultured on filter membranes with air-liquid interface methods were infected with RV-C03, and the levels of RV-C03 RNA collected from the airway surface liquid (ASL) of HNE cells were measured with a SYBR Green assay. Pretreatment of HNE cells with the specific vacuolar H+-ATPase inhibitor bafilomycin A1 reduced the RV-C03 RNA levels in the ASL; inflammatory cytokines, including interleukin (IL)-1ß, IL-6 and IL-8, in the supernatant; the mRNA expression of the RV-C receptor cadherin-related family member 3 (CDHR3) in the cells; and the number of acidic endosomes where RV-B RNA enters the cytoplasm. The levels of RV-C03 RNA in the ASL obtained from HNE cells with the CDHR3 rs6967,330 G/A genotype tended to be higher than those obtained from HNE cells with the G/G genotype. Pretreatment with the Na+/H+ exchanger inhibitor ethyl-isopropyl amiloride or either of the macrolides clarithromycin or EM900 also reduced RV-C03 RNA levels in the ASL and the number of acidic endosomes in HNE cells. In addition, significant levels of RV-A16, RV-B14 and RV-C25 RNA were detected in the ASL, and bafilomycin A1 also decreased the RV-C25 RNA levels. These findings suggest that bafilomycin A1 may reduce the release of RV-Cs and inflammatory cytokines from human airway epithelial cells. RV-Cs may be sensitive to drugs, including bafilomycin A1, that increase endosomal pH, and CDHR3 may mediate virus entry through receptor-mediated endocytosis in human airway epithelial cells.


Assuntos
Infecções por Picornaviridae , Prótons , Adenosina Trifosfatases/metabolismo , Proteínas Relacionadas a Caderinas , Caderinas/genética , Caderinas/metabolismo , Células Cultivadas , Citocinas/metabolismo , Enterovirus , Células Epiteliais , Humanos , Macrolídeos , Proteínas de Membrana/genética , RNA/metabolismo , Rhinovirus , Replicação Viral
18.
Pediatr Transplant ; 25(7): e14070, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34120389

RESUMO

BACKGROUND: LAVV have historically been avoided in children after solid organ transplantation. However, it has been reported that post-transplant, children without severe immunosuppression can generate anti-varicella antibody after immunization but the duration of the response is not clear. Furthermore, the origin of the varicella virus in immunosuppressed patients who develop varicella after vaccination is often unclear. CLINICAL PROGRESS: A female child received LAVV 30 months after a living donor liver transplant at the age of 2 months. Varicella rash appeared on the trunk 16 days after vaccination and gradually spread over the body. The patient was treated with intravenous acyclovir followed by oral therapy and recovered fully. The virus detected in blisters was derived from the vaccine-type strain. Paired sera before and after the onset of varicella showed an increase in antibody titer. However, 2 years after onset, the antibody titer decreased to undetectable again. CONCLUSIONS: This was an informative case of varicella due to vaccine strain attenuated virus. Antibody levels were not maintained over many years. Although varicella was caused by the vaccine-type strain, repeated vaccinations may be necessary for post-transplant patients who develop varicella.


Assuntos
Anticorpos Antivirais/sangue , Vacina contra Varicela/imunologia , Herpes Zoster/etiologia , Transplante de Fígado , Vacinas Atenuadas/imunologia , Pré-Escolar , Feminino , Humanos , Hospedeiro Imunocomprometido , Doadores Vivos
19.
Sci Total Environ ; 773: 145525, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33940729

RESUMO

Airborne transmission is one of the routes for the spread of COVID-19 which is caused by inhalation of smaller droplets1 containing SARS-CoV-2 (i.e., either virus-laden particulate matter: PM and/or droplet nuclei) in an indoor environment. Notably, a significant fraction of the small droplets, along with respiratory droplets, is produced by both symptomatic and asymptomatic individuals during expiratory events such as breathing, sneezing, coughing and speaking. When these small droplets are exposed to the ambient environment, they may interact with PM and may remain suspended in the atmosphere even for several hours. Therefore, it is important to know the fate of these droplets and processes (e.g., physical and chemical) in the atmosphere to better understand airborne transmission. Therefore, we reviewed existing literature focussed on the transmission of SARS-CoV-2 in the spread of COVID-19 and present an environmental perspective on why airborne transmission hasn't been very conclusive so far. In addition, we discuss various environmental factors (e.g., temperature, humidity, etc.) and sampling difficulties, which affect the conclusions of the studies focussed on airborne transmission. One of the reasons for reduced emphasis on airborne transmission could be that the smaller droplets have less number of viruses as compared to larger droplets. Further, smaller droplets can evaporate faster, exposing SARS-CoV-2 within the small droplets to the environment, whose viability may further reduce. For example, these small droplets containing SARS-CoV-2 might also physically combine with or attach to pre-existing PM so that their behaviour and fate may be governed by PM composition. Thus, the measurement of their infectivity and viability is highly uncertain due to a lack of robust sampling system to separately collect virions in the atmosphere. We believe that the present review will help to minimize the gap in our understanding of the current pandemic and develop a robust epidemiological method for mortality assessment.


Assuntos
COVID-19 , Tosse , Expiração , Humanos , Umidade , SARS-CoV-2
20.
Sensors (Basel) ; 21(7)2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33808325

RESUMO

We investigated agent-based model simulations that mimic an ant transportation system to analyze the cooperative perception and communication in the system. On a trail, ants use cooperative perception through chemotaxis to maintain a constant average velocity irrespective of their density, thereby avoiding traffic jams. Using model simulations and approximate mathematical representations, we analyzed various aspects of the communication system and their effects on cooperative perception in ant traffic. Based on the analysis, insights about the cooperative perception of ants which facilitate decentralized self-organization is presented. We also present values of communication-parameters in ant traffic, where the system conveys traffic conditions to individual ants, which ants use to self-organize and avoid traffic-jams. The mathematical analysis also verifies our findings and provides a better understanding of various model parameters leading to model improvements.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA