scholarly journals Hemagglutinin Cleavability, Acid Stability, and Temperature Dependence Optimize Influenza B Virus for Replication in Human Airways

2019 ◽  
Vol 94 (1) ◽  
Author(s):  
Manon Laporte ◽  
Annelies Stevaert ◽  
Valerie Raeymaekers ◽  
Talitha Boogaerts ◽  
Inga Nehlmeier ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Human Population ◽  
Influenza A ◽  
Influenza B Virus ◽  
Influenza B ◽  
Upper Airways ◽  
Acid Stability ◽  
Viral Hemagglutinin ◽  
B Virus ◽  
Human Airways

ABSTRACT Influenza A virus (IAV) and influenza B virus (IBV) cause yearly epidemics with significant morbidity and mortality. When zoonotic IAVs enter the human population, the viral hemagglutinin (HA) requires adaptation to achieve sustained virus transmission. In contrast, IBV has been circulating in humans, its only host, for a long period of time. Whether this entailed adaptation of IBV HA to the human airways is unknown. To address this question, we compared two seasonal IAVs (A/H1N1 and A/H3N2) and two IBVs (B/Victoria and B/Yamagata lineages) with regard to host-dependent activity of HA as the mediator of membrane fusion during viral entry. We first investigated proteolytic activation of HA by covering all type II transmembrane serine protease (TTSP) and kallikrein enzymes, many of which proved to be present in human respiratory epithelium. The IBV HA0 precursor is cleaved by a broader panel of TTSPs and activated with much higher efficiency than IAV HA0. Accordingly, knockdown of a single protease, TMPRSS2, abrogated spread of IAV but not IBV in human respiratory epithelial cells. Second, the HA fusion pH values proved similar for IBV and human-adapted IAVs (with one exception being the HA of 1918 IAV). Third, IBV HA exhibited higher expression at 33°C, a temperature required for membrane fusion by B/Victoria HA. This indicates pronounced adaptation of IBV HA to the mildly acidic pH and cooler temperature of human upper airways. These distinct and intrinsic features of IBV HA are compatible with extensive host adaptation during prolonged circulation of this respiratory virus in the human population. IMPORTANCE Influenza epidemics are caused by influenza A and influenza B viruses (IAV and IBV, respectively). IBV causes substantial disease; however, it is far less studied than IAV. While IAV originates from animal reservoirs, IBV circulates in humans only. Virus spread requires that the viral hemagglutinin (HA) is active and sufficiently stable in human airways. We resolve here how these mechanisms differ between IBV and IAV. Whereas human IAVs rely on one particular protease for HA activation, this is not the case for IBV. Superior activation of IBV by several proteases should enhance shedding of infectious particles. IBV HA exhibits acid stability and a preference for 33°C, indicating pronounced adaptation to the human upper airways, where the pH is mildly acidic and a cooler temperature exists. These adaptive features are rationalized by the long existence of IBV in humans and may have broader relevance for understanding the biology and evolution of respiratory viruses.

scholarly journals Evidence for influenza B virus hemagglutinin adaptation to the human host: high cleavability, acid-stability and preference for cool temperature

2019 ◽  
Author(s):  
Manon Laporte ◽  
Annelies Stevaert ◽  
Valerie Raeymaekers ◽  
Talitha Boogaerts ◽  
Inga Nehlmeier ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Human Population ◽  
Influenza A ◽  
Influenza B Virus ◽  
Influenza B ◽  
Upper Airways ◽  
Acid Stability ◽  
Viral Hemagglutinin ◽  
B Virus ◽  
Human Airways

AbstractInfluenza A virus (IAV) and influenza B virus (IBV) cause yearly epidemics with significant morbidity and mortality. When zoonotic IAVs enter the human population, the viral hemagglutinin (HA) requires adaptation to achieve sustained virus transmission. In contrast, IBV has been circulating in humans, its only host, for a long period of time. Whether this entailed adaptation of IBV HA to the human airways is unknown. To address this question, we compared seasonal IAV (A/H1N1 and A/H3N2) and IBV viruses (B/Victoria and B/Yamagata lineage) with regard to host-dependent activity of HA as the mediator of membrane fusion during viral entry. We first investigated proteolytic activation of HA, by covering all type II transmembrane serine protease (TTSP) and kallikrein enzymes, many of which proved present in human respiratory epithelium. Compared to IAV, the IBV HA0 precursor is cleaved by a broader panel of TTSPs and activated with much higher efficiency. Accordingly, knockdown of a single protease, TMPRSS2, was sufficient to abrogate spread of IAV but not IBV in human respiratory epithelial cells. Second, the HA fusion pH proved similar for IBV and human-adapted IAVs (one exception being HA of 1918 IAV). Third, IBV HA exhibited higher expression at 33°C, a temperature required for membrane fusion by B/Victoria HA. This indicates pronounced adaptation of IBV HA to the mildly acidic pH and cooler temperature of human upper airways. These distinct and intrinsic features of IBV HA are compatible with extensive host-adaptation during prolonged circulation of this respiratory virus in the human population.ImportanceInfluenza epidemics are caused by influenza A (IAV) and influenza B (IBV) viruses. IBV causes substantial disease, however it is far less studied than IAV. While IAV originates from animal reservoirs, IBV circulates in humans only. Virus spread requires that the viral hemagglutinin (HA) is active and sufficiently stable in human airways. We here resolve how these mechanisms differ between IBV and IAV. Whereas human IAVs rely on one particular protease for HA activation, this is not the case for IBV. Superior activation of IBV by several proteases should enhance shedding of infectious particles. IBV HA exhibits acid-stability and a preference for 33°C, indicating pronounced adaptation to the human upper airways, where the pH is mildly acidic and a cooler temperature exists. These adaptive features are rationalized by the long existence of IBV in humans, and may have broader relevance for understanding the biology and evolution of respiratory viruses.

Severe Influenza Virus Infection in Children Admitted to the PICU: Comparison of Influenza A and Influenza B Virus Infection

2021 ◽  
Author(s):  
Pınar YAZICI ÖZKAYA ◽  
Eşe Eda TURANLI ◽  
Hamdi METİN ◽  
Ayça Aydın UYSAL ◽  
Candan ÇİÇEK ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Influenza B Virus ◽  
Influenza B ◽  
Severe Influenza ◽  
B Virus

scholarly journals Clinical Investigations. Comparison of Directigen Flu A+B with Real Time PCR in the Diagnosis of Influenza / Сравнение Иммунохроматографического Метода (Directigen Flu A+B) И Теста RT-PCR При Инфекциях Гриппа

Folia Medica ◽  
2015 ◽  
Vol 57 (2) ◽  
pp. 104-110 ◽  
Author(s):  
Golubinka Bosevska ◽  
Nikola Panovski ◽  
Elizabeta Janceska ◽  
Vladimir Mikik ◽  
Irena Kondova Topuzovska ◽  
...  
Keyword(s):  
Real Time ◽  
Influenza A Virus ◽  
Real Time Pcr ◽  
Influenza A ◽  
Age Groups ◽  
Influenza Viruses ◽  
Influenza B Virus ◽  
Influenza B ◽  
B Virus ◽  
Nose And Throat

AbstractEarly diagnosis and treatment of patients with influenza is the reason why physicians need rapid high-sensitivity influenza diagnostic tests that require no complex lab equipment and can be performed and interpreted within 15 min. The Aim of this study was to compare the rapid Directigen Flu A+B test with real time PCR for detection of influenza viruses in the Republic of Macedonia. MATERIALS AND METHODS: One-hundred-eight respiratory samples (combined nose and throat swabs) were routinely collected for detection of influenza virus during influenza seasons. Forty-one patients were pediatric cases and 59 were adult. Their mean age was 23 years. The patients were allocated into 6 age groups: 0 - 4 yrs, 5 - 9 yrs, 10 - 14 yrs, 15 - 19 yrs, 20-64 yrs and > 65 yrs. Each sample was tested with Directigen Flu A+B and CDC real time PCR kit for detection and typisation/subtypisation of influenza according to the lab diagnostic protocol. RESULTS: Directigen Flu A+B identified influenza A virus in 20 (18.5%) samples and influenza B virus in two 2 (1.9%) samples. The high specificity (100%) and PPV of Directigen Flu A+B we found in our study shows that the positive results do not need to be confirmed. The overall sensitivity of Directigen Flu A+B is 35.1% for influenza A virus and 33.0% for influenza B virus. The sensitivity for influenza A is higher among children hospitalized (45.0%) and outpatients (40.0%) versus adults. CONCLUSION: Directigen Flu A+B has relatively low sensitivity for detection of influenza viruses in combined nose and throat swabs. Negative results must be confirmed.

scholarly journals Haemagglutination-inhibition antibodies against influenza A and influenza B in maternal and neonatal sera

1978 ◽  
Vol 80 (1) ◽  
pp. 13-19 ◽  
Author(s):  
N. Masurel ◽  
J. I. de Bruijne ◽  
H. A. Beuningh ◽  
H. J. A. Schouten
Keyword(s):  
Influenza Virus ◽  
Maternal Age ◽  
Influenza A ◽  
Haemagglutination Inhibition ◽  
Influenza Viruses ◽  
Influenza B Virus ◽  
Influenza B ◽  
B Virus ◽  
Duration Of Pregnancy ◽  
Pregnancy And Birth

SUMMARYHaemagglutination inhibition (HI) antibodies against the influenza viruses A/Hong Kong/8/68 (H3N2) and B/Nederland/77/66 were determined in 420 paired sera from mothers and newborns (umbilical cord sera), sampled in 1970–1.A higher concentration of antibodies against influenza A virus was found more frequently in neonatal than in maternal sera. By contrast, low titres against influenza B virus were more frequently observed in neonatal than in maternal sera. Maternal age, duration of pregnancy, and birth-weight did not affect the results of the tests.It is suggested that the titre of the newborn against an epidemic influenza virus can be predicted from that of the mother. Furthermore, the maternal titre may be an indication of the susceptibility of the newborn infant to influenza infections.

scholarly journals Influenza A and B viruses in the population of Vojvodina, Serbia

2014 ◽  
Vol 66 (1) ◽  
pp. 43-50 ◽  
Author(s):  
J. Radovanov ◽  
V. Milosevic ◽  
I. Hrnjakovic ◽  
V. Petrovic ◽  
M. Ristic ◽  
...  
Keyword(s):  
Influenza A ◽  
Respiratory Infections ◽  
Influenza Viruses ◽  
Influenza B Virus ◽  
Nasopharyngeal Swab ◽  
Influenza B ◽  
Influenza A Viruses ◽  
B Virus ◽  
Life Threatening ◽  
Seasonal Epidemic

At present, two influenza A viruses, H1N1pdm09 and H3N2, along with influenza B virus co-circulate in the human population, causing endemic and seasonal epidemic acute febrile respiratory infections, sometimes with life-threatening complications. Detection of influenza viruses in nasopharyngeal swab samples was done by real-time RT-PCR. There were 60.2% (53/88) positive samples in 2010/11, 63.4% (52/82) in 2011/12, and 49.9% (184/369) in 2012/13. Among the positive patients, influenza A viruses were predominant during the first two seasons, while influenza B type was more active during 2012/13. Subtyping of influenza A positive samples revealed the presence of A (H1N1)pdm09 in 2010/11, A (H3N2) in 2011/12, while in 2012/13, both subtypes were detected. The highest seroprevalence against influenza A was in the age-group 30-64, and against influenza B in adults aged 30-64 and >65.

scholarly journals Epidemiological and virological assessment of influenza activity in Europe during the winter 2005-2006

2007 ◽  
Vol 12 (9) ◽  
pp. 11-12 ◽  
Author(s):  
A Meijer ◽  
T J Meerhoff ◽  
L. E. Meuwissen ◽  
J Van Der Velden ◽  
W J Paget ◽  
...  
Keyword(s):  
Influenza A ◽  
New Caledonia ◽  
Influenza B Virus ◽  
Random Pattern ◽  
Clinical Activity ◽  
Influenza B ◽  
Influenza A Viruses ◽  
B Virus ◽  
Influenza Activity ◽  
Spread Pattern

Influenza activity in Europe during the winter 2005-2006 started late January - early February 2006 and first occurred in the Netherlands, France, Greece and England. Subsequently, countries were affected in a random pattern across Europe and the period of influenza activity lasted till the end of April. In contrast to the winter seasons in the period 2001-2005, no west-east pattern was detected. In 12 out of 23 countries, the consultation rates for influenza-like illness or acute respiratory infection in the winter 2005-2006 were similar or higher than in the winter 2004-2005, despite a dominance of influenza B viruses that normally cause milder disease than influenza A viruses. In the remaining 11 countries the consultation rates were lower to much lower than in the winter 2004-2005. The highest consultation rates were usually observed among children aged 0-14. The circulating influenza virus types and subtypes were distributed heterogeneously across Europe. Although the figures for total virus detections in Europe indicated a predominance of influenza B virus (58% of all virus detections), in many countries influenza B virus was predominant only early in the winter, whilst later there was a marked increase in influenza A virus detections. Among the countries where influenza A viruses were co-dominant with B viruses (9/29) or were predominant (4/29), the dominant influenza A subtype was H3 in seven countries and H1 in four countries. The vast majority of characterised influenza B viruses (90%) were similar to the B/Victoria/2/87 lineage of influenza B viruses that re-emerged in Europe in the winter 2004-2005 but were not included in the vaccine for the influenza season 2005-2006. This might help to explain the dominance of influenza B viruses in many countries in Europe during the winter 2005-2006. The influenza A(H3) and A(H1) viruses were similar to the reference strains included in the 2005-2006 vaccine, A/California/7/2004 (H3N2) and A/New Caledonia/20/99 (H1N1), respectively. In conclusion, the 2005-2006 influenza epidemic in Europe was characterised by moderate clinical activity, a heterogeneous spread pattern across Europe, and a variable virus dominance by country, although an overall dominance of influenza B viruses that did not match the virus strain included in the vaccine was observed.

scholarly journals Serum High-Mobility-Group Box 1 as a Biomarker and a Therapeutic Target during Respiratory Virus Infections

mBio ◽  
2018 ◽  
Vol 9 (2) ◽  
Author(s):  
Mira C. Patel ◽  
Kari Ann Shirey ◽  
Marina S. Boukhvalova ◽  
Stefanie N. Vogel ◽  
Jorge C. G. Blanco
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
High Mobility ◽  
Influenza B Virus ◽  
Influenza B ◽  
Lung Pathology ◽  
B Virus ◽  
Cotton Rats

ABSTRACT Host-derived “danger-associated molecular patterns” (DAMPs) contribute to innate immune responses and serve as markers of disease progression and severity for inflammatory and infectious diseases. There is accumulating evidence that generation of DAMPs such as oxidized phospholipids and high-mobility-group box 1 (HMGB1) during influenza virus infection leads to acute lung injury (ALI). Treatment of influenza virus-infected mice and cotton rats with the Toll-like receptor 4 (TLR4) antagonist Eritoran blocked DAMP accumulation and ameliorated influenza virus-induced ALI. However, changes in systemic HMGB1 kinetics during the course of influenza virus infection in animal models and humans have yet to establish an association of HMGB1 release with influenza virus infection. To this end, we used the cotton rat model that is permissive to nonadapted strains of influenza A and B viruses, respiratory syncytial virus (RSV), and human rhinoviruses (HRVs). Serum HMGB1 levels were measured by an enzyme-linked immunosorbent assay (ELISA) prior to infection until day 14 or 18 post-infection. Infection with either influenza A or B virus resulted in a robust increase in serum HMGB1 levels that decreased by days 14 to 18. Inoculation with the live attenuated vaccine FluMist resulted in HMGB1 levels that were significantly lower than those with infection with live influenza viruses. RSV and HRVs showed profiles of serum HMGB1 induction that were consistent with their replication and degree of lung pathology in cotton rats. We further showed that therapeutic treatment with Eritoran of cotton rats infected with influenza B virus significantly blunted serum HMGB1 levels and improved lung pathology, without inhibiting virus replication. These findings support the use of drugs that block HMGB1 to combat influenza virus-induced ALI. IMPORTANCE Influenza virus is a common infectious agent causing serious seasonal epidemics, and there is urgent need to develop an alternative treatment modality for influenza virus infection. Recently, host-derived DAMPs, such as oxidized phospholipids and HMGB1, were shown to be generated during influenza virus infection and cause ALI. To establish a clear link between influenza virus infection and HMGB1 as a biomarker, we have systematically analyzed temporal patterns of serum HMGB1 release in cotton rats infected with nonadapted strains of influenza A and B viruses and compared these patterns with a live attenuated influenza vaccine and infection by other respiratory viruses. Towards development of a new therapeutic modality, we show herein that blocking serum HMGB1 levels by Eritoran improves lung pathology in influenza B virus-infected cotton rats. Our study is the first report of systemic HMGB1 as a potential biomarker of severity in respiratory virus infections and confirms that drugs that block virus-induced HMGB1 ameliorate ALI.

scholarly journals The importance of distinguishing COVID-19 from more common respiratory illnesses

2020 ◽  
Vol 148 ◽  
Author(s):  
Wei Zhao ◽  
Xingzhi Xie ◽  
Jun Liu
Keyword(s):  
Computed Tomography ◽  
Influenza A ◽  
Influenza B Virus ◽  
Influenza B ◽  
Imaging Findings ◽  
Influenza A Viruses ◽  
Respiratory Illnesses ◽  
B Virus ◽  
Virus Pneumonia

Abstract We recruited 1591 patients who presented to our fever clinics from 23 January 2020 to 16 February 2020. The different imaging findings between COVID-19 pneumonia and influenza A viruses, influenza B virus pneumonia were also investigated. Most patients were infected by influenza A and B viruses in the flu-season. A laboratory kit is urgently needed to test different viruses simultaneously. Computed tomography can help early screen suspected patients with COVID-19 and differentiate different virus-related pneumonia.

scholarly journals Detection of severe acute respiratory syndrome coronavirus 2 and influenza viruses based on CRISPR-Cas12a

2020 ◽  
pp. 153537022096379
Author(s):  
Oraphan Mayuramart ◽  
Pattaraporn Nimsamer ◽  
Somruthai Rattanaburi ◽  
Naphat Chantaravisoot ◽  
Kritsada Khongnomnan ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Severe Acute Respiratory Syndrome ◽  
Influenza A ◽  
Limit Of Detection ◽  
Cross Reactivity ◽  
Influenza Viruses ◽  
Influenza B Virus ◽  
Influenza B ◽  
Influenza Virus A ◽  
B Virus

Due to the common symptoms of COVID-19, patients are similar to influenza-like illness. Therefore, the detection method would be crucial to discriminate between SARS-CoV-2 and influenza virus-infected patients. In this study, CRISPR-Cas12a-based detection was applied for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus, and influenza B virus which would be a practical and attractive application for screening of patients with COVID-19 and influenza in areas with limited resources. The limit of detection for SARS-CoV-2, influenza A, and influenza B detection was 10, 103, and 103 copies/reaction, respectively. Moreover, the assays yielded no cross-reactivity against other respiratory viruses. The results revealed that the detection of influenza virus and SARS-CoV-2 by using RT-RPA and CRISPR-Cas12a technology reaches 96.23% sensitivity and 100% specificity for SARS-CoV-2 detection. The sensitivity for influenza virus A and B detections was 85.07% and 94.87%, respectively. In addition, the specificity for influenza virus A and B detections was approximately 96%. In conclusion, the RT-RPA with CRISPR-Cas12a assay was an effective method for the screening of influenza viruses and SARS-CoV-2 which could be applied to detect other infectious diseases in the future.

scholarly journals Co-circulation of the two influenza B lineages during 13 consecutive influenza surveillance seasons in Italy, 2004–2017

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Simona Puzelli ◽  
◽  
Angela Di Martino ◽  
Marzia Facchini ◽  
Concetta Fabiani ◽  
...  
Keyword(s):  
Influenza A ◽  
Respiratory Illness ◽  
Influenza Surveillance ◽  
Influenza B Virus ◽  
Influenza B ◽  
Virus Infections ◽  
Ha Gene ◽  
B Virus ◽  
B Lineage ◽  
Trivalent Vaccine

Abstract Background Since 1985, two antigenically distinct lineages of influenza B viruses (Victoria-like and Yamagata-like) have circulated globally. Trivalent seasonal influenza vaccines contain two circulating influenza A strains but a single B strain and thus provide limited immunity against circulating B strains of the lineage not included in the vaccine. In this study, we describe the characteristics of influenza B viruses that caused respiratory illness in the population in Italy over 13 consecutive seasons of virological surveillance, and the match between the predominant influenza B lineage and the vaccine B lineage, in each season. Methods From 2004 to 2017, 26,886 laboratory-confirmed influenza cases were registered in Italy, of which 18.7% were type B. Among them, the lineage of 2465 strains (49%) was retrieved or characterized in this study by a real-time RT-PCR assay and/or sequencing of the hemagglutinin (HA) gene. Results Co-circulation of both B lineages was observed each season, although in different proportions every year. Overall, viruses of B/Victoria and B/Yamagata lineages caused 53.3 and 46.7% of influenza B infections, respectively. A higher proportion of infections with both lineages was detected in children, and there was a declining frequency of B/Victoria detections with age. A mismatch between the vaccine and the predominant influenza B lineage occurred in eight out of thirteen influenza seasons under study. Considering the seasons when B accounted for > 20% of all laboratory-confirmed influenza cases, a mismatch was observed in four out of six seasons. Phylogenetic analysis of the HA1 domain confirmed the co-circulation of both lineages and revealed a mixed circulation of distinct evolutionary viral variants, with different levels of match to the vaccine strains. Conclusions This study contributes to the understanding of the circulation of influenza B viruses in Italy. We found a continuous co-circulation of both B lineages in the period 2004–2017, and determined that children were particularly vulnerable to Victoria-lineage influenza B virus infections. An influenza B lineage mismatch with the trivalent vaccine occurred in about two-thirds of cases.

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