Plataforma laboratorial para monitorear el SARS-CoV-2 basada en la vigilancia de influenza y otros virus respiratorios en Perú / Laboratory platform for monitoring SARS-CoV-2 based on surveillance of influenza and other respiratory viruses in Peru

RESUMEN En el Perú, la pandemia de la COVID-19 ha evidenciado la utilidad de tener un sistema de vigilancia laboratorial estructurado y en funcionamiento desde hace 22 años, basado en la vigilancia de influenza; inicialmente en modalidad de unidades centinela, y después fortaleciéndose e innovándose, con recursos propios y con apoyo externo, para generar información de calidad. Se han implementado avances biotecnológicos para la confirmación diagnóstica e incrementado las capacidades de la red nacional de laboratorios, manteniendo la eficiencia, considerando las diversas y complejas realidades de los niveles regionales, y superando dificultades de comunicación y articulación entre instituciones. Resulta necesario consolidar este sistema, con trabajo colaborativo y coordinado entre sus componentes, impulsando su eficacia y oportunidad y promoviendo la vigilancia genómica de nuevos virus y variantes, como actualmente ocurre con el SARS-CoV-2.

ABSTRACT In Peru, the COVID-19 pandemic demonstrated the usefulness of having a structured laboratory surveillance system that has been operational for 22 years, based on influenza surveillance; initially in the form of sentinel units, and later strengthened and innovated, with its own resources and with external support, to provide quality information. Biotechnological advances have been implemented for diagnostic confirmation and the capacity of the national laboratory network has been expanded, maintaining efficiency, considering the diverse and complex realities of each region, and overcoming difficulties regarding communication and articulation between institutions. It is necessary to consolidate this system, with collaborative and coordinated work between its components, boosting its effectiveness and timeliness and promoting genomic surveillance of new viruses and variants, as is currently the case with SARS-CoV-2.

Effect and mechanism of acupoint injection on influenza A virus induced pneumonia in mice / 中国针灸

OBJECTIVE@#To investigate the effect and mechanism of acupoint injection with 0.1% vitamin C+vitamin B complex solution (VC+VBCo) at "Tiantu" (CV 22), "Quchi" (LI 11) and "Zusanli" (ST 36) in mouse model of pneumonia induced by influenza A virus (A/PR/8/34 [H1N1], PR8).@*METHODS@#Sixty male ICR mice were randomized into 6 groups, i.e. control group, model group, acupoint injection group, intraperitoneal injection group, non-target point group and ribavirin group, 10 mice in each one. Except the control group, the pneumonia models were induced by slow nasal dripping PR8 virus in the other groups. On the 2nd day of experiment, VC+VBCo solution, 40 μL was injected at "Tiantu" (CV 22), "Quchi" (LI 11, left) and "Zusanli" (ST 36, left) in the acupoint injection group; VC+VBCo solution, 120 μL was injected intraperitoneally in the intraperitoneal injection group; VC+VBCo solution, 40 μL was injected at non-target acupoints (0.5 cm away from "Tiantu" [CV 22] to the left side, "Quchi" [LI 11, left] and "Zusanli" [ST 36, left]) in the non-target point group; and ribavirin solution, 120 μL was injected intraperitoneally in the ribavirin group. The intervention was delivered once daily, for consecutive 7 days. Three parallel experiments were undertaken. The mean death rate and survival time were assessed in each group, the body mass and lung index were compared among groups. Using HE staining, the morphology of lung tissue was observed; and with real-time fluorescence quantitative PCR, viral load in lung tissue was detected. The concentrations of inflammatory factors (tumor necrosis factor α [TNF-α], interleukin [IL]-1β, IL-10) were detected in lung tissue of each group using ELISA; and those of oxidative stress markers (superoxide dismutase [SOD], glutathione peroxidase [GSH-Px], malondialdehyde [MDA]) were detected with chemiluminescence method.@*RESULTS@#Compared with the control group, the body mass was decreased and lung index was increased in the model group (P<0.01). In comparison with the model group, body mass was increased in the acupoint injection group (P<0.05), lung index was reduced in the acupoint injection group the and ribavirin group (P<0.05); the mean death rate was decreased and the mean survival time prolonged in the mice of the acupoint injection group (P<0.01, P<0.05); and the mean death rate was reduced in the mice of the ribavirin group (P<0.05). In the model group, the alveolar structure was not integral, the alveolar septum was thickened, inflammatory cells were infiltrated and red blood cells exudated seriously (P<0.01). Compared with the model group, in the acupoint injection group and the ribavirin group, the alveolar structure was integral, the thickened alveolar septum was alleviated; and the infiltration of inflammatory cells and the exudation of red blood cells were reduced remarkably. The viral load was reduced in the mice of the ribavirin group when compared with the model group (P<0.01). Compared with the control group, the concentrations of TNF-α, IL-1β and MDA in lung tissue were increased and those of IL-10, SOD and GSH-Px were reduced in the model group (P<0.01). In the acupoint injection group and the ribavirin group, the concentrations of TNF-α, IL-1β and MDA were reduced in lung tissue and those of IL-10, SOD and GSH-Px were increased (P<0.05, P<0.01) when compared with the model group.@*CONCLUSION@#Acupoint injection with VC+VBCo solution may alleviate inflammatory responses and oxidative stress in lung tissue of the PR8-induced pneumonia mice, improve survival rate and prolong the survival time in the case of no effect of the viral load.

Distribution and gene characteristics of H3, H4 and H6 subtypes of low pathogenic avian influenza viruses in environment related avian influenza viruses during 2014-2021 in China / 中华预防医学杂志

Objective: To analyze the characteristics of low pathogenic H3, H4 and H6 subtypes of avian influenza viruses in environment related avian influenza viruses in China from 2014 to 2021. Methods: Surveillance sites were located in 31 provinces, autonomous region and municipalities to collect environmental samples related to avian influenza, detect the nucleic acid detection of influenza A virus, isolate virus, deeply sequence, analyze pathogenicity related molecular sites, and determine the distribution and variation characteristics of common H3, H4 and H6 subtypes of avian influenza virus in different regions, places and sample types. Results: A total of 388 645 samples were collected. The positive rate of low pathogenic H3 (0.56‰) and H6 (0.53‰) was higher than that of H4 (0.09‰). The positive rate of H4 subtype virus in live poultry market was higher than that in other places, and the difference was statistically significant. The positive rate of H3 and H6 subtypes in sewage samples was higher than that in other samples, and the difference was statistically significant. The positive rate of H3, H4 and H6 viruses in the south was higher than that in the north, and the difference was statistically significant. December was the most active time for virus. The analysis of pathogenicity related molecular sites showed that H3, H4 and H6 subtypes of viruses combined with avian influenza virus receptors, and some gene sites related to increased pathogenicity had mutations. Conclusion: The H3, H4 and H6 subtypes of low pathogenic avian influenza viruses have a high isolation positive rate in the live poultry market and sewage. The distribution of the three subtypes of viruses has obvious regional and seasonal characteristics, and the genetic characteristics still show the feature of low pathogenic avian influenza.

A clinical study of influenza A virus infection with neurological symptoms in children / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features of children with influenza A virus infection and neurological symptoms.@*METHODS@#A retrospective analysis was performed for the clinical data of children with laboratory-confirmed influenza A and neurological symptoms who were treated in Xi'an Children's Hospital Affiliated to Xi'an Jiaotong University from January to December, 2019.@*RESULTS@#A total of 895 children were diagnosed with influenza A, among whom 291 had neurological symptoms. Boys had a significantly higher incidence rate of influenza A than girls (@*CONCLUSIONS@#There is a high incidence rate of neurological symptoms in children with influenza A, and seizures are the most common symptom. Most of the patients with neurological symptoms tend to have a good prognosis, but those with ANE may have a poor prognosis.

Agents of pneumonia in slaughtered pigs in southern Brazil / Agentes patogênicos de pneumonia em suínos abatidos no sul do Brasil

A high prevalence of pneumonic lesions has been reported to affect slaughtered pigs in southern Brazil. In order to identify which microorganisms have been causing those lesions, 30 pig lungs presenting pneumonic gross lesions were collected from five different slaughterhouses, totaling 150 lungs. Samples for bacterial isolation, molecular, histopathologic and immunohistochemistry (IHC) evaluation were taken from each lung. The pneumonic lesion scoring ranged from 1.53 to 2.83. The most frequent histopathological lesions found was the concomitant Influenza A virus (IAV) and Mycoplasma hyopneumoniae infection, corresponding to 55.3% (83/150), and Pasteurella multocida type A was isolated in 54.2% (45/83) of these cases. In 102 samples (68%), there was histopathologic suggestion of involvement of more than one infectious agent. M. hyopneumoniae was the most frequent agent associated with pneumonic lesions, being present in 92.1% (94/102) of the lungs with coinfections, followed by IAV in 89.2% (91/102). Besides the coinfections, IAV lesions were observed also in six samples without another pathogenic microorganism detected. A total of 46 samples with acute and subacute IAV suspected lesions in histopathological examination were assessed for IHC and real time RT-PCR for IAV. A total of 35% (16/46) of them were positive by IHC and 13% (6/46) by real time RT-PCR. Regarding M. hyopneumoniae, 79.3% (119/150) of samples were positive by qPCR and 84.9% (101/119) of them also presented M. hyopneumoniae suspected lesions in the histopathological examination. The results of this study suggest the importance of IAV in respiratory diseases in finishing pigs, even though this virus is more frequently reported in the nursery phase. In addition, our results emphasize the importance of lung coinfections in finishing pigs.(AU)

Lesões sugestivas de pneumonia são frequentemente encontradas em altas prevalências em suínos abatidos no sul do Brasil. Para identificar quais microrganismos causam essas lesões, foram coletados 30 pulmões de suínos com lesão macroscópica sugestiva de pneumonia em cinco frigoríficos diferentes, totalizando 150 pulmões. Amostras para isolamento bacteriano, avaliação molecular, histopatológica e imuno-histoquímica (IHC) foram coletadas de cada pulmão. O escore de lesão pulmonar variou entre 1,53 a 2,83. O achado histopatológico mais observado foi a lesão sugestiva de infecção concomitante pelo vírus Influenza A (IAV) e Mycoplasma (M.) hyopneumoniae, correspondendo a 55,3% (83/150), e em 54,2% (45/83) desses casos Pasteurella (P.) multocida tipo A foi isolado. Em 102 amostras (68%), houve lesão histopatológica sugestiva do envolvimento de mais de um agente infeccioso. M. hyopneumoniae foi o microrganismo mais frequente associado a lesões de pneumonia, estando presente em 92,1% (94/102) dos pulmões com coinfecções, seguido de IAV, que foi encontrado em 89,2% (91/102). Além das coinfecções, lesões de IAV foram observadas em mais seis amostras que não aparentavam envolvimento de outro agente infeccioso. Um total de 46 amostras com suspeita de lesão aguda e subaguda de IAV no exame histopatológico foram avaliadas para IHC e RT-PCR em tempo real para IAV e 35% (16/46) delas foram positivas por IHC e 13% (6/46) foram positivas por RT-PCR em tempo real. Com relação a M. hyopneumoniae, 79,3% (119/150) das amostras foram positivas por qPCR e 84,9% (101/119) delas também apresentaram lesões suspeitas de M. hyopneumoniae no exame histopatológico. Os resultados deste trabalho sugerem a importância do IAV como agente causador de pneumonias em suínos de terminação, embora esse vírus seja mais frequentemente relatado na fase de creche. Além disso, os achados deste trabalho demonstram a presença frequente de coinfecções pulmonares em suínos de terminação.(AU)

Influenza A and B in a cohort of outpatient children and adolescent with influenza like-illness during two consecutive influenza seasons

ABSTRACT Introduction Influenza is an important cause of morbimortality worldwide. Although people at the extremes of age have a greater risk of complications, influenza has been more frequently investigated in the elderly than in children, and inpatients than outpatients. Yearly vaccination with trivalent or quadrivalent vaccines is the main strategy to control influenza. Objectives Determine the clinical and molecular characteristics of influenza A and B infections in children and adolescents with influenza-like illness (ILI). Methods: A cohort of outpatient children and adolescents with ILI was followed for 20 months. Influenza was diagnosed with commercial multiplex PCR platforms. Results: 179 patients had 277 episodes of ILI, being 79 episodes of influenza A and 20 episodes of influenza B. Influenza A and B cases were mild and had similar presentation. Phylogenetic tree of influenza B viruses showed that 91.6% belonged to the B/Yamagata lineage, which is not included in trivalent vaccines. Conclusions: Influenza A and B are often detected in children and adolescents with ILI episodes, with similar and mild presentation in outpatients. The mismatch between the circulating influenza viruses and the trivalent vaccine offered in Brazil may have contributed to the high frequency of influenza A and B in this population.

Down-regulation of miR-155 inhibits inflammatory response in human pulmonary microvascular endothelial cells infected with influenza A virus by targeting sphingosine-1-phosphate receptor 1 / 中华医学杂志(英文版)

BACKGROUND@#Endothelial cells play a key role in the cytokine storm caused by influenza A virus. MicroRNA-155 (miR-155) is an important regulator in inflammation. Its role in the inflammatory response to influenza A infection, however, has yet to be elucidated. In this study, we explored the role as well as the underlying mechanism of miR-155 in the cytokine production in influenza A-infected endothelial cells.@*METHODS@#Human pulmonary microvascular endothelial cells (HPMECs) were infected with the influenza A virus strain H1N1. The efficiency of H1N1 infection was confirmed by immunofluorescence. The expression levels of proinflammatory cytokines and miR-155 were determined using real-time polymerase chain reaction. A dual-luciferase reporter assay characterized the interaction between miR-155 and sphingosine-1-phosphate receptor 1 (S1PR1). Changes in the target protein levels were determined using Western blot analysis.@*RESULTS@#MiR-155 was elevated in response to the H1N1 infection in HPMECs (24 h post-infection vs. 0 h post-infection, 3.875 ± 0.062 vs. 1.043 ± 0.013, P = 0.001). Over-expression of miR-155 enhanced inflammatory cytokine production (miR-155 mimic vs. negative control, all P < 0.05 in regard of cytokine levels) and activation of nuclear factor kappa B in infected HPMECs (miR-155 mimic vs. negative control, P = 0.004), and down-regulation of miR-155 had the opposite effect. In addition, S1PR1 was a direct target of miR-155 in the HPMECs. Inhibition of miR-155 enhanced the expression of the S1PR1 protein. Down-regulation of S1PR1 decreased the inhibitory effect of the miR-155 blockade on H1N1-induced cytokine production and nuclear factor kappa B activation in HPMECs.@*CONCLUSION@#MiR-155 maybe modulate influenza A-induced inflammatory response by targeting S1PR1.

Influenza A virus exposure may cause increased symptom severity and deaths in coronavirus disease 2019 / 中华医学杂志(英文版)

BACKGROUND@#The coronavirus disease 2019 (COVID-19) outbreak occurred during the flu season around the world. This study aimed to analyze the impact of influenza A virus (IAV) exposure on COVID-19.@*METHODS@#Seventy COVID-19 patients admitted to the hospital during January and February 2020 in Wuhan, China were included in this retrospective study. Serum tests including respiratory pathogen immunoglobulin M (IgM) and inflammation biomarkers were performed upon admission. Patients were divided into common, severe, and critical types according to disease severity. Symptoms, inflammation indices, disease severity, and fatality rate were compared between anti-IAV IgM-positive and anti-IAV IgM-negative groups. The effects of the empirical use of oseltamivir were also analyzed in both groups. For comparison between groups, t tests and the Mann-Whitney U test were used according to data distribution. The Chi-squared test was used to compare disease severity and fatality between groups.@*RESULTS@#Thirty-two (45.71%) of the 70 patients had positive anti-IAV IgM. Compared with the IAV-negative group, the positive group showed significantly higher proportions of female patients (59.38% vs. 34.21%, χ = 4.43, P = 0.035) and patients with fatigue (59.38% vs. 34.21%, χ = 4.43, P = 0.035). The levels of soluble interleukin 2 receptor (median 791.00 vs. 1075.50 IU/mL, Z = -2.70, P = 0.007) and tumor necrosis factor α (median 10.75 vs. 11.50 pg/mL, Z = -2.18, P = 0.029) were significantly lower in the IAV-positive group. Furthermore, this group tended to have a higher proportion of critical patients (31.25% vs. 15.79%, P = 0.066) and a higher fatality rate (21.88% vs. 7.89%, P = 0.169). Notably, in the IAV-positive group, patients who received oseltamivir had a significantly lower fatality rate (0 vs. 36.84%, P = 0.025) compared with those not receiving oseltamivir.@*CONCLUSIONS@#The study suggests that during the flu season, close attention should be paid to the probability of IAV exposure in COVID-19 patients. Prospective studies with larger sample sizes are needed to clarify whether IAV increases the fatality rate of COVID-19 and to elucidate any benefits of empirical usage of oseltamivir.

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.

Serologic evidence of seasonal influenza A and B in HIV patients on combined antiretroviral therapy in Lagos, Nigeria

Background: Influenza and HIV are endemic in Nigeria but there is no epidemiological data on the co-infection of influenza A and B among HIV patients.Objective: We investigated seasonal influenza A and B, and co-infection among HIV patients on combined antiretroviral therapy (cART) in Lagos, Nigeria.Methods: In a prospective cross-sectional study, clear sera collected from 174 HIV-positive patients between August and September 2018 were analysed for immunoglobulin M-specific antibodies to seasonal influenza A subtypes H1N1 and H3N2, and influenza B by enzyme immunoassay. Results: A total of 39.7% (69/174) of HIV patients were seropositive for influenza A or B viruses with 84.1% (58/69) being positive for influenza A, 13.04% (9/69) seropositive for both influenza A and B, and only 2.9% (2/69) positive for influenza B mono-infection. Median age was 44 (mean 45, mode 40, range 18­74) years. The 41­50 years age group had the highest seroprevalence (39.1%; 27/69). Seropositivity was highest among women (65.2%; 45/69). A total of 88.4% (61/69) of HIV patients seropositive for influenza A or B were on fixed dose cART, while 73.9% (51/69) were virologically suppressed. Furthermore, 27.5% (19/69) were immunocompromised, of which 21.1% (4/19) were severely immunosuppressed (cluster of differentiation 4 < 200 cells/mm>3).Conclusion: Influenza A and B was prevalent among HIV patients on cART, which may predispose them to life-threatening complications. We recommend strong advocacy on the need to reduce the risk of exposure to influenza and for the provision of an influenza vaccine in Nigeria

Eosinophilic Enteritis Presenting as Massive Ascites after Influenza A Virus Infection in a Young Female / 대한소화기학회지

Eosinophilic gastrointestinal disorder (EGID) is an uncommon disease that is accompanied by intestinal eosinophil infiltration without a secondary cause of eosinophilia. Eosinophilic enteritis is a secondary portion of EGID that can present a range of gastrointestinal symptoms according to the affected depth of the intestinal layer. The subserosal type of eosinophilic enteritis presenting as ascites is relatively rarer than the mucosal type. In general, eosinophilic enteritis occurs in patients with food allergies, but its mechanism is unclear. The authors experienced a 29-year-old female patient with a large amount of ascites with diarrhea and abdominal pain. The patient was diagnosed with an influenza A infection one week earlier. Peripheral eosinophilia (absolute eosinophil count: 6,351 cells/mm³) and eosinophilic ascites (97% of white blood cells in the ascites are eosinophil) were present. Abdominal CT revealed a large amount of ascites and edematous changes in the ileum and ascending colon wall. A diagnosis of eosinophilic enteritis was confirmed as eosinophilic ascites by paracentesis, with eosinophil infiltration of the bowel wall by an endoscopic biopsy. The patient's symptoms improved rapidly after using steroids. To the best of the author's knowledge, this is the first report of eosinophilic enteritis with massive ascites after an influenza A virus infection in a Korean adult.

Postinfectious Glomerulonephritis Associated with Pneumococcus and Influenza A Virus Infection in a Child: a Case Report and Literature Review

Postinfectious glomerulonephritis (PIGN) is most commonly caused by Streptococcus pyogenes in children, but PIGN associated with other pathogens has been described in the literature. A previously healthy 6-year-old boy was admitted with complaints of cough, fever, and right chest pain. The patient was diagnosed with pneumococcal bacteremia and influenza A virus infection and treated with antibiotics and antiviral agent. During hospitalization, generalized edema, hematuria, proteinuria, and increased blood pressure were observed; therefore, we started administering diuretics. The boy was discharged with gross hematuria, and even microscopic hematuria disappeared 14 weeks after discharge. We report a case of PIGN associated with bacteremic pneumococcal pneumonia and influenza A virus infection in children. A urine test and blood pressure measurement should be considered for the early detection of PIGN in children with pneumococcal or influenza A virus infection when they present with nephritic symptoms.

Neuraminidase Inhibitors from the Fruiting Body of Glaziella splendens

Neuraminidase (NA) cleaves the glycosidic bond linkages of sialic acids to release the mature virions from infected cells and has been an attractive therapeutic target for anti-influenza agents. In our ongoing investigation of NA inhibitors in mushroom extracts, we found that the extract the fruiting body of Glaziella splendens potently inhibited neuraminidase. The fruiting bodies of G. splendens were extracted and partitioned successively with hexane, ethyl acetate, and butanol. The ethyl acetate soluble-layer was subjected to silica gel and Sephadex LH-20 column chromatographies, and MPLC to obtain five compounds (1–5). Their structures were determined by spectroscopic methods. NA inhibitory activity of these compounds was evaluated using NAs from recombinant rvH1N1, H3N2, and H5N1 influenza A viruses. One compound (1) was elucidated as a new azaphilone derivative, and four compounds (2–5) were identified as entonaemin A, comazaphilone D, rubiginosin A, and entonaemin B, respectively. Compounds 3 and 4 showed considerable inhibitory activity against three types of neuraminidases with the IC₅₀ values of 30.9, 41.8, and 35.7 µM for 3 and 46.5, 50.4, and 29.9 µM for 4, respectively. This study reveals that the fruiting bodies of G. splendens possess azaphilone derivatives with the NA inhibitory activity. This is the first report on the isolation of neuraminidase inhibitors from the fruiting bodies of G. splendens.

Antibody responses after vaccination against equine influenza in Korea in 2016–2018 / 대한수의학회지

Equine influenza (EI) is the main cause of respiratory illness in equines across the globe and is caused by equine influenza A virus (EIV-A), which has impacted the equine industry internationally because of the marginal mortality and high morbidity. In the present study, the immune responses after equine influenza vaccination were evaluated in 4,144 horses in Korea using the hemagglutination inhibition (HI) assay. The equine influenza virus (EIV), A/equine/South Africa/4/03 (H3N8), was used as the antigen in the HI assay. The mean seropositive rates were 89.2% (97.4% in 2016, 77.6% in 2017, and 92.4% in 2018). This paper highlights the advances in understanding the effects of vaccines and control strategies for mitigating the emerging menace by EIV.

Development of a HA1-specific enzyme-linked immunosorbent assay against pandemic influenza virus A H1N1

PURPOSE: Enzyme-linked immunosorbent assay (ELISA) has been used in the diverse field to evaluate influenza virus infection; for the surveillance, diagnosis, efficacy evaluation, and development of the vaccine. The aim of this study was to establish an ELISA for detecting HA strain-specific antibodies using recombinant pandemic A H1N1 (pH1N1) HA1 (rHA1) protein. MATERIALS AND METHODS: rHA1 was produced in baculovirus system. The clinical performance of the developed ELISA was validated using human serum samples, by comparison with standard methods for detecting a neutralizing antibody; hemagglutination inhibition (HI) assay and microneutralization test (MNT). The ability of the ELISA system to evaluate the efficacy test of an influenza vaccine was explored by measuring antibody levels in the serum of vaccinated mice. RESULTS: Our ELISA could detect anti-rHA1 antibody in influenza-infected patients and vaccinated subjects. Compared to HI assay and MNT as reference methods, our method showed good performance in detection of anti-rHA1 antibody. Detection of the anti-rHA1 antibody in vaccinated mice and its correlation with titers in HI assay was also proved in a mice model. CONCLUSION: An ELISA system using rHA1 of pH1N1 influenza virus was developed, and showed good clinical performance in diagnosis of influenza virus infection and evaluation of the vaccination efficacy in both human and animal models.

Evaluation of Protective Immunity of Peptide Vaccines Composed of a 15-mer N-terminal Matrix Protein 2 and a Helper T-Cell Epitope Derived from Influenza A Virus

The matrix protein 2 of influenza A virus (IFAV) has a relatively conserved ectodomain (M2e) composed of 23 amino acids, and M2e-based vaccines have been suggested to induce broad protective immunity in mice. In this study, we investigated whether N-terminal sequence of M2e (nM2e)-based vaccines with more conserved nM2e could induce influenza viral neutralizing activity. We constructed linear peptide vaccines with an nM2e sequence for PR8 virus (nM2Pr) connected to a probable 17-mer IFAV-derived helper T-cell epitope (ThE: T1, T2, or T3) at its N- or C-terminus. The peptide vaccines induced significant production of nM2e Abs regardless of either type or location of the ThE-epitope in BALB/c mice, while only T3 was effective in C57BL/6 mice. The Abs against nM2Pr-T3 elicited broader binding affinities to the nM2e peptides derived from various IFAVs than those against T3-nM2Pr. In addition, the nM2e-based vaccines efficiently protected the immunized mice from the lethal challenge of PR8 virus. These results suggest that the more conserved nM2e without cysteine will be useful for development of universal peptide vaccines than M2e.

Benign Acute Childhood Myositis Associated with Influenza B Virus / 대한신경근육질환학회지

Influenza B virus infections appear to be more common extra-respiratory tract symptoms, compared to influenza A virus infections. Benign acute childhood myositis (BACM) is a benign disease that is caused mainly by many viruses like influenza A or B virus infection. Usually BACM is fully cured with only supportive treatment without unnecessary investigation or invasive procedure. This report describes an eight-year-old boy with acute bilateral calf pain and walking difficulty who diagnosed with BACM after influenza B virus infection.