scholarly journals Protein-bound sialic acid in saliva contributes directly to salivary anti-influenza virus activity

2021 ◽  
Author(s):  
Kaori Kobayashi ◽  
Chika Shono ◽  
Takuya Mori ◽  
Hidefumi Kitazawa ◽  
Noriyasu Ota ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Influenza A ◽  
Significant Positive Correlation ◽  
Influenza Infection ◽  
Respiratory Viruses ◽  
Biological Factor ◽  
Virus Activity ◽  
Individual Variations ◽  
Antiviral Activities ◽  
Direct Regulator

ABSTRACTThe oral cavity is an entrance for respiratory viruses, such as influenza. Recently, saliva has been shown to exert both antimicrobial and antiviral activities. Thus, saliva may be a biological factor that contributes to the prevention of influenza infection. However, the actual salivary anti-influenza A virus (IAV) activity in individuals and its determinant factors are unknown. By assessing individual variations in salivary anti-IAV activity in 92 people using an established new high-throughput system in this study, we found that the anti-IAV activity varied widely between individuals and showed a significant positive correlation with protein-bound sialic acid (BSA) level (ρ=0.473; p < 0.001). Furthermore, the anti-IAV activity of saliva with enzymatically reduced BSA content was significantly lower. These results indicate that BSA is a direct regulator of salivary anti-IAV activity and is a determinant of individual differences. Additionally, after comparing the anti-IAV activity across the groups by age, anti-IAV activity in young people (aged 5–19 years) were lower than in adults aged 20–59 years and elderly people aged 60–79 years. Our study suggests that BSA levels in saliva may be important in preventing influenza infection.

scholarly journals Local Respiratory Viral Surveillance Can Focus Public Health Interventions to Decrease Influenza Disease Burden

2021 ◽  
Vol 186 (Supplement_1) ◽  
pp. 76-81
Author(s):  
Elena Crouch ◽  
Jonathan Gonzalez ◽  
Erin Jacobs ◽  
Kurt Schaecher ◽  
Margaret Kehl ◽  
...  
Keyword(s):  
Influenza A ◽  
Disease Burden ◽  
Medical Center ◽  
Influenza Infection ◽  
Respiratory Viruses ◽  
Current Data ◽  
Influenza B ◽  
Preventative Measures ◽  
The Individual ◽  
Viral Surveillance

ABSTRACT Background Respiratory viruses are an important cause of nonbattle injury disease and contribute to the top seven reasons for medical encounters. In the absence of vaccines that provide complete protection against these viruses, viral surveillance can identify disease burden and target virus-specific preventative measures. Influenza infection, in particular, has significant adverse effects on force readiness. Methods We tracked the frequency of 16 respiratory viruses at Walter Reed National Military Medical Center tested for during routine patient care using multiplex polymerase chain reaction and rapid antigen testing. We collected data on the date and location of the testing, as well as the age of the individual tested from two consecutive respiratory viral seasons. Results During the first year of data compilation (2017-2018), 2556 tests were performed; 342 (13.4%) were positive for influenza A and 119 (4.7%) were positive for influenza B. After influenza, the most common families of viruses identified were rhino/enterovirus (490 [19.2%]). During the second year (2018-2019), 4,458 tests were run; 564 (12.7%) were positive for influenza A and 35 (0.79%) were positive for influenza B, while rhino/enterovirus was identified in 690 (15.4%). Influenza peaked early during the 2017-2018 season and later during the 2018-2019 season. Importantly, during the 2017-2018 season, the vaccine was less effective for the H3N2 strain circulating that year and viral surveillance quickly identified a hospital-specific outbreak and a larger disease burden. This was in contrast to the 2018-2019 vaccine which exhibited higher effectiveness for circulating strains. Conclusion Our data highlight the seasonality of respiratory viruses with a focus on influenza. By tracking respiratory viruses in Department of Defense communities, we may be able to predict when influenza may cause the greatest burden for distinct organizational regions and prescribe with greater precision preventative protocols by location, as well as rapidly determine vaccine efficacy. Our current data suggest that when vaccine strains are mismatched, rapid upfront targeting of antivirals may be warranted, but when the vaccine strains are better matched, late season peaks of disease may indicate waning immunity and should be monitored.

IN VITRO ANTI-VIRAL ACTIVITY OF ETHANOL EXTRACT FROM IXERIS CHINENSIS AGAINST INFLUENZA VIRUS

2015 ◽  
Vol 41 (01) ◽  
pp. 11-19
Author(s):  
Chih-Hsueh Yang ◽  
Duen-Huey Tan ◽  
Ting-Ting Jong ◽  
Chi-Luan Wen ◽  
Shih-Lan Hsu ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Influenza Infection ◽  
Ethanol Extract ◽  
Pharmacological Properties ◽  
Virus Activity ◽  
Exploitation And Utilization ◽  
Prevention And Treatment ◽  
Influenza A Virus Infection

Ixeris chinensis (Thunb.) Nakai (I. chinensis), a commonly used Taiwanese herbal medicine that exhibits various pharmacological properties, has been used to prepare a traditional Chinese medicine composition for prevention and treatment of influenza A virus infection. In this study, the in vitro anti-influenza virus activity of I. chinensis was evaluated. The result showed that the 50% ethanol extract from I. chinensis significantly increased the viability of the DF-1 cells that were infected with the H6N1 influenza virus. This extract also suppressed the synthesis of viral nucleoprotein (NP) and inhibited the growth of the H6N1 virus in DF-1 cells. Further, the 50% ethanol extract from I. chinensis inhibited the neuraminidase (NA) activity of the H6N1 virus. These findings provide important information for exploitation and utilization of I. chinensis in treatment of influenza infection.

scholarly journals SALIENT FEATURES OF CIRCULATING RESPIRATORY VIRUSES IN THE PRE– AND PANDEMIC INFLUENZA AND COVID–19 SEASONS

2021 ◽  
Author(s):  
I. V. Kiseleva ◽  
N. V. Larionova ◽  
E. P. Grigorieva ◽  
A. D. Ksenafontov ◽  
M. Al Farroukh ◽  
...  
Keyword(s):  
Pandemic Influenza ◽  
Influenza A ◽  
Influenza Infection ◽  
Opportunity To Learn ◽  
Respiratory Viruses ◽  
Influenza Viruses ◽  
Effective Prevention ◽  
Pdm09 Virus ◽  
Influenza A H1n1 ◽  
Syncytial Virus

Abstract. A wide variety of zoonotic viruses that can cross the interspecies barrier promote the emergence of new, potentially pandemic viruses in the human population that was often accompanied by the disappearance of existing circulating strains. Among the various reasons underlying this phenomenon is the strengthening of populational immunity by expanding the immune layer of the population and improving the means and methods of medical care. However, “Natura abhorret vacuum”, and new pathogens come to replace disappearing pathogens. In the past ten years, there have been two critical events – the pandemic spread of the swine influenza A (H1N1) pdm09 virus in 2009 and the novel SARS–CoV–2 coronavirus in 2019, providing scientists with a unique opportunity to learn more about a relationship between respiratory viruses and their pathogenesis. Together with viruses of pandemic significance, a large number of seasonal respiratory viruses circulate, which contribute to the structure of human morbidity, and co–infections aggravate the condition of the illness. In the conditions of the spread of new viruses with unexplored characteristics, in the absence of means of prevention and therapy, it is especially important to prevent the aggravation of morbidity due to mixed infections. Here we review the mutual involvement of pandemic influenza A(H1N1)pdm09 and SARS–CoV–2 coronavirus and seasonal respiratory viruses in the epidemic process, discuss some issues related to their spread, potential causes affecting the spread and severity of the morbidity. The given facts, testify to the existence of seasonality and temporal patterns of the beginning and end of the circulation of respiratory viruses. Interestingly, the beginning of the circulation of the pandemic influenza A(H1N1)pdm09 virus led to a shift in the timing and intensity of circulation of some respiratory viruses, which is probably caused by the existence of "replication conflicts" between them, and did not affect others. Co–infection with SARS–CoV–2–19 and other respiratory viruses, especially respiratory syncytial virus and rhinoviruses, was quite often observed. At the current stage, no aggravating effect of influenza on the course of COVID–19 in mixed infection has been established. Whether this is due to the mild course of influenza infection in the 2020 epidemic season, or the competitive impact of SARS–CoV–2 on influenza viruses is not yet clear. Experts are still at the stage of accumulating facts and working on creating means of effective prevention and treatment of the new coronavirus infection.

#10: Tropism, Susceptibility, and Infectivity of Differentiated Human Tonsillar Epithelial Cells by Different Influenza Viruses

2021 ◽  
Vol 10 (Supplement_2) ◽  
pp. S7-S7
Author(s):  
Faten A Okda* ◽  
Richard Webby
Keyword(s):  
Influenza Virus ◽  
Sialic Acid ◽  
Epithelial Cells ◽  
Influenza A ◽  
Influenza Infection ◽  
Influenza Viruses ◽  
H3n2 Virus ◽  
Ciliated Cells ◽  
Human Tonsil ◽  
Sialic Acid Receptors

Abstract Introduction Influenza viruses cause significant socioeconomic impact due to annual outbreaks and pandemic risks. Human tonsil epithelium cells (HTEC) are a heterogeneous group of actively differentiating epithelia comprising stratified squamous epithelium and reticulated crypt cells with abundant keratin expression. Hypothesis We hypothesized that the tonsils are a primary site for influenza infection and sustained viral replication. Methods and Results Primary HTEC (ScienCell Research Laboratories) were grown using an air-liquid interface and infected apically with different influenza viruses at various MOIs to measure viral growth kinetics. These cells were highly differentiated, with subpopulations of cells including ciliated, non-ciliated cells and specialized cells with secretory functions. There was a heterogenous distribution of both human-like (α2,6-linked) and avian-like (α2,3-linked) sialic acid receptors. The HTEC surface and crypts were lined with pseudostratified columnar ciliated cells possessing both α2,6-linked and α2,3-linked sialic acid receptors that were interrupted by patches of reticular epithelial cells. The HTEC epithelial cells were permissive for growth of influenza A and B viruses. A subset of cells, mostly ciliated cells, underwent apoptosis while others including non-ciliated cells remained intact despite being positive for influenza virus nucleoprotein. Interestingly, differences were seen between subtypes with colocalization of H3N2 virus and non-ciliated cells while H1N1 virus mostly associated with ciliated cells. Conclusion Our results implicated human tonsillar crypt epithelium as a site for influenza virus replication. The tonsil epithelium cell culture differentiated system provides a valuable in vitro model for studying cellular tropism, infectivity, cytokines immune response and the pathogenesis of influenza viruses for better development of effective universal vaccine and therapies against different strains of influenza viruses.

scholarly journals Co-colonization byStreptococcus pneumoniaeandStaphylococcus aureusin the throat during acute respiratory illnesses

2016 ◽  
Vol 144 (16) ◽  
pp. 3507-3519 ◽  
Author(s):  
V. DE LASTOURS ◽  
R. MALOSH ◽  
K. RAMADUGU ◽  
U. SRINIVASAN ◽  
S. DAWID ◽  
...  
Keyword(s):  
Odds Ratio ◽  
Influenza A ◽  
Influenza Infection ◽  
Respiratory Illness ◽  
Respiratory Viruses ◽  
Acute Respiratory Illness ◽  
Negative Group ◽  
Negative Interaction ◽  
Respiratory Illnesses ◽  
Colonization Dynamics

SUMMARYPneumonia due to eitherStreptococcus pneumoniae(Sp) orStaphylococcus aureus(Sa) accounts for most mortality after influenza and acute respiratory illness (ARI). Because carriage precedes infection, we estimated Sp and Sa carriage to examine the co-colonization dynamics between Sp, Sa and respiratory viruses in the presence of ARI in the oropharynx. We tested oropharyngeal specimens of community subjects (aged ⩾2 years) with ARI for the presence of influenza A and B, 11 other common respiratory viruses, Sp and Sa, using real-time PCR. A total of 338 participants reported 519 ARI episodes of which 119 (35%) carried Sp, 52 (13%) carried Sa and 25 (7%) carried both. Thirty-five subjects tested positive for influenza, of which 14 (40%) carried Sp and six (17%) carried Sa, significantly more than in the influenza-negative group (P= 0·03 andP= 0·04, respectively). In subjects infected by any virus compared to those with no virus, Sp carriage (39·2%vs. 27·9%,P= 0·03) but not Sa carriage (11·6%vs. 14%,P= 0·6) was more frequent. For children, when Sa was present, Sp carriage tended to be less frequent than expected given the presence of viral infection, but not significantly [observed relative risk 1·14, 95% confidence interval (CI) 0·4–3·1; with a relative excess risk due to interaction of –0·11]. Independent of age, Sp carriers were more likely to return that season with subsequent ARI (odds ratio 2·14, 95% CI 1·1–4·3,P= 0·03). Both Sp and Sa carriage rates in the oropharynx increase during influenza infection in children. However, no negative interaction between Sp and Sa was observed. Sp carriers are more likely to suffer subsequent ARI episodes than non-carriers.

scholarly journals Differential Expression of Serum Exosome microRNAs and Cytokines in Influenza A and B Patients Collected in the 2016 and 2017 Influenza Seasons

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 149
Author(s):  
Sreekumar Othumpangat ◽  
William G. Lindsley ◽  
Donald H. Beezhold ◽  
Michael L. Kashon ◽  
Carmen N. Burrell ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Influenza A ◽  
Influenza Infection ◽  
Cell Types ◽  
Airway Epithelial Cells ◽  
Differentially Expressed ◽  
Influenza B ◽  
Airway Epithelial ◽  
Monocyte Chemoattractant Protein 1 ◽  
Novel Approach

MicroRNAs (miRNAs) have remarkable stability and are key regulators of mRNA transcripts for several essential proteins required for the survival of cells and replication of the virus. Exosomes are thought to play an essential role in intercellular communications by transporting proteins and miRNAs, making them ideal in the search for biomarkers. Evidence suggests that miRNAs are involved in the regulation of influenza virus replication in many cell types. During the 2016 and 2017 influenza season, we collected blood samples from 54 patients infected with influenza and from 30 healthy volunteers to identify the potential role of circulating serum miRNAs and cytokines in influenza infection. Data comparing the exosomal miRNAs in patients with influenza B to healthy volunteers showed 76 miRNAs that were differentially expressed (p < 0.05). In contrast, 26 miRNAs were differentially expressed between patients with influenza A (p < 0.05) and the controls. Of these miRNAs, 11 were commonly expressed in both the influenza A and B patients. Interferon (IFN)-inducing protein 10 (IP-10), which is involved in IFN synthesis during influenza infection, showed the highest level of expression in both influenza A and B patients. Influenza A patients showed increased expression of IFNα, GM-CSF, interleukin (IL)-13, IL-17A, IL-1β, IL-6 and TNFα, while influenza B induced increased levels of EGF, G-CSF, IL-1α, MIP-1α, and TNF-β. In addition, hsa-miR-326, hsa-miR-15b-5p, hsa-miR-885, hsa-miR-122-5p, hsa-miR-133a-3p, and hsa-miR-150-5p showed high correlations to IL-6, IL-15, IL-17A, IL-1β, and monocyte chemoattractant protein-1 (MCP-1) with both strains of influenza. Next-generation sequencing studies of H1N1-infected human lung small airway epithelial cells also showed similar pattern of expression of miR-375-5p, miR-143-3p, 199a-3p, and miR-199a-5p compared to influenza A patients. In summary, this study provides insights into the miRNA profiling in both influenza A and B virus in circulation and a novel approach to identify the early infections through a combination of cytokines and miRNA expression.

scholarly journals Influenza and other respiratory viral infections associated with absence from school among schoolchildren in Pittsburgh, Pennsylvania, USA: a cohort study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jonathan M. Read ◽  
Shanta Zimmer ◽  
Charles Vukotich ◽  
Mary Lou Schweizer ◽  
David Galloway ◽  
...  
Keyword(s):  
Cohort Study ◽  
Viral Infections ◽  
Influenza Infection ◽  
Respiratory Viruses ◽  
Influenza B ◽  
Mixed Effect ◽  
School Aged Children ◽  
Respiratory Viral Infections ◽  
Day Programs ◽  
K 12

Abstract Background Information on the etiology and age-specific burden of respiratory viral infections among school-aged children remains limited. Though school aged children are often recognized as driving the transmission of influenza as well as other respiratory viruses, little detailed information is available on the distribution of respiratory infections among children of different ages within this group. Factors other than age including gender and time spent in school may also be important in determining risk of infection but have been little studied in this age group. Methods We conducted a cohort study to determine the etiology of influenza like illness (ILI) among 2519 K–12 students during the 2012–13 influenza season. We obtained nasal swabs from students with ILI-related absences. Generalized linear mixed-effect regressions determined associations of outcomes, including ILI and laboratory-confirmed respiratory virus infection, with school grade and other covariates. Results Overall, 459 swabs were obtained from 552 ILI–related absences. Respiratory viruses were found in 292 (63.6%) samples. Influenza was found in 189 (41.2%) samples. With influenza B found in 134 (70.9%). Rates of influenza B were significantly higher in grades 1 (10.1, 95% CI 6.8–14.4%), 2 (9.7, 6.6–13.6%), 3 (9.3, 6.3–13.2%), and 4 (9.9, 6.8–13.8%) than in kindergarteners (3.2, 1.5–6.0%). After accounting for grade, sex and self-reported vaccination status, influenza B infection risk was lower among kindergarteners in half-day programs compared to kindergarteners in full-day programs (OR = 0.19; 95% CI 0.08–0.45). Conclusions ILI and influenza infection is concentrated in younger schoolchildren. Reduced infection by respiratory viruses is associated with a truncated school day for kindergarteners but this finding requires further investigation in other grades and populations.

scholarly journals Thapsigargin Is a Broad-Spectrum Inhibitor of Major Human Respiratory Viruses: Coronavirus, Respiratory Syncytial Virus and Influenza A Virus

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 234
Author(s):  
Sarah Al-Beltagi ◽  
Cristian Alexandru Preda ◽  
Leah V. Goulding ◽  
Joe James ◽  
Juan Pu ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Respiratory Syncytial Virus ◽  
Influenza A Virus ◽  
Broad Spectrum ◽  
Influenza A ◽  
Respiratory Viruses ◽  
Influenza Viruses ◽  
Virus Challenge ◽  
2009 H1n1 ◽  
Syncytial Virus

The long-term control strategy of SARS-CoV-2 and other major respiratory viruses needs to include antivirals to treat acute infections, in addition to the judicious use of effective vaccines. Whilst COVID-19 vaccines are being rolled out for mass vaccination, the modest number of antivirals in use or development for any disease bears testament to the challenges of antiviral development. We recently showed that non-cytotoxic levels of thapsigargin (TG), an inhibitor of the sarcoplasmic/endoplasmic reticulum (ER) Ca2+ ATPase pump, induces a potent host innate immune antiviral response that blocks influenza A virus replication. Here we show that TG is also highly effective in blocking the replication of respiratory syncytial virus (RSV), common cold coronavirus OC43, SARS-CoV-2 and influenza A virus in immortalized or primary human cells. TG’s antiviral performance was significantly better than remdesivir and ribavirin in their respective inhibition of OC43 and RSV. Notably, TG was just as inhibitory to coronaviruses (OC43 and SARS-CoV-2) and influenza viruses (USSR H1N1 and pdm 2009 H1N1) in separate infections as in co-infections. Post-infection oral gavage of acid-stable TG protected mice against a lethal influenza virus challenge. Together with its ability to inhibit the different viruses before or during active infection, and with an antiviral duration of at least 48 h post-TG exposure, we propose that TG (or its derivatives) is a promising broad-spectrum inhibitor against SARS-CoV-2, OC43, RSV and influenza virus.

scholarly journals Influenza vaccine failure in the tropics: a retrospective cohort study of waning effectiveness

2020 ◽  
Vol 148 ◽  
Author(s):  
B. E. Young ◽  
T. M. Mak ◽  
L. W. Ang ◽  
S. Sadarangani ◽  
H. J. Ho ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Cohort Study ◽  
Influenza Vaccine ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Influenza Infection ◽  
Winter Season ◽  
Temperate Climate ◽  
Vaccine Failure ◽  
Virus Activity

Abstract Influenza vaccine effectiveness (VE) wanes over the course of a temperate climate winter season but little data are available from tropical countries with year-round influenza virus activity. In Singapore, a retrospective cohort study of adults vaccinated from 2013 to 2017 was conducted. Influenza vaccine failure was defined as hospital admission with polymerase chain reaction-confirmed influenza infection 2–49 weeks after vaccination. Relative VE was calculated by splitting the follow-up period into 8-week episodes (Lexis expansion) and the odds of influenza infection in the first 8-week period after vaccination (weeks 2–9) compared with subsequent 8-week periods using multivariable logistic regression adjusting for patient factors and influenza virus activity. Records of 19 298 influenza vaccinations were analysed with 617 (3.2%) influenza infections. Relative VE was stable for the first 26 weeks post-vaccination, but then declined for all three influenza types/subtypes to 69% at weeks 42–49 (95% confidence interval (CI) 52–92%, P = 0.011). VE declined fastest in older adults, in individuals with chronic pulmonary disease and in those who had been previously vaccinated within the last 2 years. Vaccine failure was significantly associated with a change in recommended vaccine strains between vaccination and observation period (adjusted odds ratio 1.26, 95% CI 1.06–1.50, P = 0.010).

scholarly journals Potent sialic acid inhibitors that target influenza A virus hemagglutinin

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu-Jen Chang ◽  
Cheng-Yun Yeh ◽  
Ju-Chien Cheng ◽  
Yu-Qi Huang ◽  
Kai-Cheng Hsu ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Antiviral Activity ◽  
Binding Site ◽  
Influenza A Virus ◽  
Receptor Binding ◽  
Influenza A ◽  
The United States ◽  
Ligand Complex ◽  
Receptor Binding Site ◽  
Computational Strategy

AbstractEradicating influenza A virus (IAV) is difficult, due to its genetic drift and reassortment ability. As the infectious cycle is initiated by the influenza glycoprotein, hemagglutinin (HA), which mediates the binding of virions to terminal sialic acids moieties, HA is a tempting target of anti-influenza inhibitors. However, the complexity of the HA structure has prevented delineation of the structural characterization of the HA protein–ligand complex. Our computational strategy efficiently analyzed > 200,000 records of compounds held in the United States National Cancer Institute (NCI) database and identified potential HA inhibitors, by modeling the sialic acid (SA) receptor binding site (RBS) for the HA structure. Our modeling revealed that compound NSC85561 showed significant antiviral activity against the IAV H1N1 strain with EC50 values ranging from 2.31 to 2.53 µM and negligible cytotoxicity (CC50 > 700 µM). Using the NSC85561 compound as the template to generate 12 derivatives, robust bioassay results revealed the strongest antiviral efficacies with NSC47715 and NSC7223. Virtual screening clearly identified three SA receptor binding site inhibitors that were successfully validated in experimental data. Thus, our computational strategy has identified SA receptor binding site inhibitors against HA that show IAV-associated antiviral activity.

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