scholarly journals ANP32 Proteins Are Essential for Influenza Virus Replication in Human Cells

2019 ◽  
Vol 93 (17) ◽  
Author(s):  
Ecco Staller ◽  
Carol M. Sheppard ◽  
Peter J. Neasham ◽  
Bhakti Mistry ◽  
Thomas P. Peacock ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Replication ◽  
Influenza A ◽  
Polymerase Activity ◽  
Human Cells ◽  
Host Factors ◽  
Influenza B Virus ◽  
Influenza B ◽  
B Virus ◽  
Influenza Virus Replication

ABSTRACT ANP32 proteins have been implicated in supporting influenza virus replication, but most of the work to date has focused on the ability of avian Anp32 proteins to overcome restriction of avian influenza polymerases in human cells. Using a CRISPR approach, we show that the human acidic nuclear phosphoproteins (ANPs) ANP32A and ANP32B are functionally redundant but essential host factors for mammalian-adapted influenza A virus (IAV) and influenza B virus (IBV) replication in human cells. When both proteins are absent from human cells, influenza polymerases are unable to replicate the viral genome, and infectious virus cannot propagate. Provision of exogenous ANP32A or ANP32B recovers polymerase activity and virus growth. We demonstrate that this redundancy is absent in the murine Anp32 orthologues; murine Anp32A is incapable of recovering IAV polymerase activity, while murine Anp32B can do so. Intriguingly, IBV polymerase is able to use murine Anp32A. We show, using a domain swap and point mutations, that the leucine-rich repeat (LRR) 5 region comprises an important functional domain for mammalian ANP32 proteins. Our approach has identified a pair of essential host factors for influenza virus replication and can be harnessed to inform future interventions. IMPORTANCE Influenza virus is the etiological agent behind some of the most devastating infectious disease pandemics to date, and influenza outbreaks still pose a major threat to public health. Influenza virus polymerase, the molecule that copies the viral RNA genome, hijacks cellular proteins to support its replication. Current anti-influenza drugs are aimed against viral proteins, including the polymerase, but RNA viruses like influenza tend to become resistant to such drugs very rapidly. An alternative strategy is to design therapeutics that target the host proteins that are necessary for virus propagation. Here, we show that the human proteins ANP32A and ANP32B are essential for influenza A and B virus replication, such that in their absence cells become impervious to the virus. We map the proviral activity of ANP32 proteins to one region in particular, which could inform future intervention.

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 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 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 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 DRIFT OF INFLUENA A(H3N2) VIRUS: BIOLOGICAL, ANTIGENIC AND GENETIC PROPERTIES IN EPIDEMIC SEASON 2016-2017 IN RUSSIA AND COUNTRIES OF THE NOTHERN HEMYSPHERE

2018 ◽  
Vol 63 (2) ◽  
pp. 61-68 ◽  
Author(s):  
D. K. Lvov ◽  
E. I. Burtseva ◽  
E. S. Kirillova ◽  
L. V. Kolobukhina ◽  
E. A. Mukasheva ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Northern Hemisphere ◽  
Influenza A ◽  
H3n2 Virus ◽  
Research Centre ◽  
Federal State ◽  
Influenza B Virus ◽  
Influenza B ◽  
Epidemic Season ◽  
B Virus

The article presents the features of the influenza virus circulation for the period from October 2016 to May 2017 in some territories of Russia collaborating with the D.I. Ivanovsky Institute of Virology, Federal State Budgetary Institution “N.F. Gamaleya Federal Research Centre for Epidemiology and Microbiology”, Ministry of Health of the Russian Federation. One of the 2016-2017 season’s peculiarities in Russia and countries of the Northern hemisphere was the earlier start of an increase in ARD morbidity with peak indexes reached towards the end of December 2016 - January 2017. First, influenza A(H3N2) virus was predominant; then, it was followed by influenza B virus activity observed until the end of the season. The indexes of morbidity were higher than in the previous season, while the rates of hospitalization and mortality were lower, lethal cases being detected in persons 65 years old and older. Epidemic strains of influenza A(H3N2) virus belonged to 3c.2a genetic group, reference strain A/Hong Hong/4408/2014, and its subgroup 3c.2a1, reference A/Bolzano/7/2016, that are antigenically similar. Strains of influenza B virus were antigenically similar to the B/Brisbane/60/2008 vaccine virus. Strains were sensitive to oseltamivir and zanamivir. The share participation of non-influenza ARI viruses was similar to preliminary epidemic seasons. WHO has issued recommendations for influenza virus vaccines composition for 2017-2018 for the Northern hemisphere.

scholarly journals Chimeric Hemagglutinin Constructs Induce Broad Protection against Influenza B Virus Challenge in the Mouse Model

2017 ◽  
Vol 91 (12) ◽  
Author(s):  
Megan E. Ermler ◽  
Ericka Kirkpatrick ◽  
Weina Sun ◽  
Rong Hai ◽  
Fatima Amanat ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Antiviral Drug ◽  
Antigenic Drift ◽  
Influenza B Virus ◽  
Influenza B ◽  
Virus Infections ◽  
Lethal Challenge ◽  
Public Health Burden ◽  
B Virus

ABSTRACT Seasonal influenza virus epidemics represent a significant public health burden. Approximately 25% of all influenza virus infections are caused by type B viruses, and these infections can be severe, especially in children. Current influenza virus vaccines are an effective prophylaxis against infection but are impacted by rapid antigenic drift, which can lead to mismatches between vaccine strains and circulating strains. Here, we describe a broadly protective vaccine candidate based on chimeric hemagglutinins, consisting of globular head domains from exotic influenza A viruses and stalk domains from influenza B viruses. Sequential vaccination with these constructs in mice leads to the induction of broadly reactive antibodies that bind to the conserved stalk domain of influenza B virus hemagglutinin. Vaccinated mice are protected from lethal challenge with diverse influenza B viruses. Results from serum transfer experiments and antibody-dependent cell-mediated cytotoxicity (ADCC) assays indicate that this protection is antibody mediated and based on Fc effector functions. The present data suggest that chimeric hemagglutinin-based vaccination is a viable strategy to broadly protect against influenza B virus infection. IMPORTANCE While current influenza virus vaccines are effective, they are affected by mismatches between vaccine strains and circulating strains. Furthermore, the antiviral drug oseltamivir is less effective for treating influenza B virus infections than for treating influenza A virus infections. A vaccine that induces broad and long-lasting protection against influenza B viruses is therefore urgently needed.

scholarly journals Prevalence of Influenza Virus Type and Subtype at Siriraj Hospital, Bangkok, Thailand During 2013 - 2017

2020 ◽  
Vol 43 (3) ◽  
pp. 1-7
Author(s):  
Nattapol Narong ◽  
Siriwat Manajit ◽  
Sirikarn Athipanyasil ◽  
Niracha Athipanyasilp ◽  
Ruengpung Sutthent ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Respiratory Illness ◽  
Influenza B Virus ◽  
Influenza B ◽  
Influenza A H1n1 ◽  
B Virus ◽  
Siriraj Hospital

Background: Influenza A (pandemic and seasonal H1/H3) and influenza B viruses were the predominant circulating seasonal influenza strains. Following its massive outbreak in 2009 globally, including Thailand, influenza A (H1N1) pdm09 viruses have replaced the previous seasonal H1 strain and become one of the circulating strains ever since. Both influenza A and B viruses are highly contagious and potentially cause respiratory illness ranging from mild to severe. Objective: To determine the prevalence of types and subtypes of circulating influenza virus strains in Bangkok, Thailand during 2013 - 2017. Methods: The 4385 nasopharyngeal wash specimens were collected from patients presented with influenza-like illness from January 2013 to December 2017 at Siriraj Hospital, Bangkok, Thailand. Influenza virus types and subtypes were determined using real-time RT-PCR technique. Clinical characteristics of patients infected with influenza A viruses and influenza B virus were compared and analyzed. Results: Of 4385 nasopharyngeal wash specimens, the prevalence of influenza virus infection during 2013 - 2017 was 18.22% (n = 799). Of 799 influenza-positive samples, 608 (76.09%) and 191 (23.90%) samples were positive for influenza A and influenza B viruses, respectively. Most patients were presented with fever, cough, and runny nose; however, patients infected with influenza A virus generally had higher severity than those with influenza B virus infection (P < .05). Conclusions: The findings provided the characteristics of influenza virus types and subtypes at Siriraj Hospital, Bangkok, Thailand during 2013 - 2017. Sporadic cases of influenza occurred all year round, but the incidence peaked in March 2014 and August 2017. The outcomes of this study are potentially useful for prevention, treatment, and disease monitoring.  

scholarly journals COMPARISONS OF INFLUENZA VIRUS STRAINS FROM THREE EPIDEMICS

1947 ◽  
Vol 86 (5) ◽  
pp. 367-381 ◽  
Author(s):  
George K. Hirst
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Strain Differences ◽  
Significant Degree ◽  
Influenza B Virus ◽  
Influenza B ◽  
B Virus ◽  
The Difference ◽  
Virus Strains ◽  
Better Than

Some of the peculiarities of strains of influenza A and B virus from two epidemics have been described. The influenza B virus of 1945–46, when compared with influenza A virus, proved to be much more difficult to isolate from human sources by any known means. Its adaptation to the chick embryo (by any route) or to mice was much slower than that of A virus. It did not keep nearly as well on storage at –72°C. either in throat garglings or as passage material. Its adaptation to amniotic growth was usually much better than to allantoic growth even after repeated allantoic passages. It failed to show primary evidence of occurring in the O form, although many of the secondary O characteristics were present and persisted. Its titer in throat washings was not demonstrably high as compared with certain strains of A virus, which were demonstrated in garglings at dilutions of 10–5 and 10–6. The antigenic patterns of influenza A strains from two epidemics were compared. No antigenic differences of significant degree were found among the strains of either epidemic and the difference between the strains of the two epidemics was very slight. A similar study was made of the influenza B strains of the epidemic of 1945–46. This also showed complete lack of significant strain differences. The implications of these findings for influenza prophylaxis are discussed.

scholarly journals Universal Influenza B Vaccine Based on the Maturational Cleavage Site of the Hemagglutinin Precursor

2005 ◽  
Vol 79 (12) ◽  
pp. 7380-7388 ◽  
Author(s):  
Elisabetta Bianchi ◽  
Xiaoping Liang ◽  
Paolo Ingallinella ◽  
Marco Finotto ◽  
Michael A. Chastain ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Cleavage Site ◽  
Influenza A ◽  
Influenza B Virus ◽  
Influenza B ◽  
Continuous Manufacturing ◽  
Lethal Challenge ◽  
Universal Vaccine ◽  
B Virus

ABSTRACT Conventional influenza vaccines can prevent infection, but their efficacy depends on the degree of antigenic “match” between the strains used for vaccine preparation and those circulating in the population. A universal influenza vaccine based on invariant regions of the virus, able to provide broadly cross-reactive protection, without requiring continuous manufacturing update, would solve a major medical need. Since the temporal and geographical dominance of the influenza virus type and/or subtype (A/H3, A/H1, or B) cannot yet be predicted, a universal vaccine, like the vaccines currently in use, should include both type A and type B influenza virus components. However, while encouraging preclinical data are available for influenza A virus, no candidate universal vaccine is available for influenza B virus. We show here that a peptide conjugate vaccine, based on the highly conserved maturational cleavage site of the HA0 precursor of the influenza B virus hemagglutinin, can elicit a protective immune response against lethal challenge with viruses belonging to either one of the representative, non-antigenically cross-reactive influenza B virus lineages. We demonstrate that protection by the HA0 vaccine is mediated by antibodies, probably through effector mechanisms, and that a major part of the protective response targets the most conserved region of HA0, the P1 residue of the scissile bond and the fusion peptide domain. In addition, we present preliminary evidence that the approach can be extended to influenza A virus, although the equivalent HA0 conjugate is not as efficacious as for influenza B virus.

scholarly journals Effects of Absolute Humidity, Relative Humidity, Temperature, and Wind Speed on Influenza Activity in Toronto, Ontario, Canada

2019 ◽  
Vol 85 (6) ◽  
Author(s):  
Adriana Peci ◽  
Anne-Luise Winter ◽  
Ye Li ◽  
Saravanamuttu Gnaneshan ◽  
Juan Liu ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Relative Humidity ◽  
Influenza A ◽  
Absolute Humidity ◽  
Influenza B Virus ◽  
Influenza B ◽  
Virus Infections ◽  
B Virus ◽  
Influenza Activity ◽  
Temperate Climates

ABSTRACT The occurrence of influenza in different climates has been shown to be associated with multiple meteorological factors. The incidence of influenza has been reported to increase during rainy seasons in tropical climates and during the dry, cold months of winter in temperate climates. This study was designed to explore the role of absolute humidity (AH), relative humidity (RH), temperature, and wind speed (WS) on influenza activity in the Toronto, ON, Canada, area. Environmental data obtained from four meteorological stations in the Toronto area over the period from 1 January 2010 to 31 December 2015 were linked to patient influenza data obtained for the same locality and period. Data were analyzed using correlation, negative binomial regressions with linear predictors, and splines to capture the nonlinear relationship between exposure and outcomes. Our study found a negative association of both AH and temperature with influenza A and B virus infections. The effect of RH on influenza A and B viruses was controversial. Temperature fluctuation was associated with increased numbers of influenza B virus infections. Influenza virus was less likely to be detected from community patients than from patients tested as part of an institutional outbreak investigation. This could be more indicative of nosocomial transmission rather than climactic factors. The nonlinear nature of the relationship of influenza A virus with temperature and of influenza B virus with AH, RH, and temperature could explain the complexity and variation between influenza A and B virus infections. Predicting influenza activity is important for the timing of implementation of disease prevention and control measures as well as for resource allocation. IMPORTANCE This study examined the relationship between environmental factors and the occurrence of influenza in general. Since the seasonality of influenza A and B viruses is different in most temperate climates, we also examined each influenza virus separately. This study reports a negative association of both absolute humidity and temperature with influenza A and B viruses and tries to understand the controversial effect of RH on influenza A and B viruses. This study reports a nonlinear relation between influenza A and B viruses with temperature and influenza B virus with absolute and relative humidity. The nonlinear nature of these relations could explain the complexity and difference in seasonality between influenza A and B viruses, with the latter predominating later in the season. Separating community-based specimens from those obtained during outbreaks was also a novel approach in this research. These findings provide a further understanding of influenza virus transmission in temperate climates.

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