Structural Basis for Ubiquitin-like ISG 15 Protein Binding to the NS1 Protein of Influenza B Virus: A Protein–Protein Interaction Function That Is Not Shared by the Corresponding N-terminal Domain of the NS1 Protein of Influenza A Virus

ABSTRACTInfluenza A and B virus infections both cause a host innate immunity response. Here, we report that the robust production of type I and III interferons (IFNs), IFN-stimulated genes, and proinflammatory factors can be induced by influenza B virus rather than influenza A virus infection in alveolar epithelial (A549) cells during early infection. This response is mainly dependent on the retinoic acid-inducible gene I (RIG-I)-mediated signaling pathway. Infection by influenza B virus promotes intense Lys63-linked ubiquitination of RIG-I, resulting in cytokine eruption. It is known that the influenza A virus NS1 protein (NS1-A) interacts with RIG-I and TRIM25 to suppress the activation of RIG-I-mediated signaling. However, the present results indicate that the influenza B virus NS1 protein (NS1-B) is unable to interact with RIG-I but engages in the formation of a RIG-I/TRIM25/NS1-B ternary complex. Furthermore, we demonstrate that the N-terminal RNA-binding domain (RBD) of NS1-B is responsible for interaction with TRIM25 and that this interaction blocks the inhibitory effect of the NS1-B C-terminal effector domain (TED) on RIG-I ubiquitination. Our findings reveal a novel mechanism for the host cytokine response to influenza B virus infection through regulatory interplay between host and viral proteins.IMPORTANCEInfluenza B virus generally causes local mild epidemics but is occasionally lethal to individuals. Existing studies describe the broad characteristics of influenza B virus epidemiology and pathology. However, to develop better prevention and treatments for the disease, determining the concrete molecular mechanisms of pathogenesis becomes pivotal to understand how the host reacts to the challenge of influenza B virus. Thus, we aimed to characterize the host innate immune response to influenza B virus infection. Here, we show that vigorous Lys63-linked ubiquitination of RIG-I and cytokine eruption dependent on RIG-I-mediated signal transduction are induced by virus infection. Additionally, TRIM25 positively regulates RIG-I-mediated signaling by ablating the inhibitory function of NS1-B on RIG-I ubiquitination.

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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 ◽

10.1515/folmed-2015-0027 ◽

2015 ◽

Vol 57 (2) ◽

pp. 104-110 ◽

Cited By ~ 4

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.

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STUDIES ON THE MECHANISM OF ADAPTATION OF INFLUENZA VIRUS TO MICE

Journal of Experimental Medicine ◽

10.1084/jem.86.5.357 ◽

1947 ◽

Vol 86 (5) ◽

pp. 357-366 ◽

Cited By ~ 53

Author(s):

George K. Hirst

Keyword(s):

Influenza A Virus ◽

Influenza A ◽

High Titer ◽

Strain Difference ◽

Mouse Lung ◽

Influenza B Virus ◽

Influenza B ◽

Difference Problem ◽

B Virus ◽

Repeated Passage

1. When strains of influenza A virus which have been isolated in chick embryos are introduced into the mouse lung, the virus multiplies readily and achieves initially a titer which is as high as is even obtained, even after repeated passage. The high initial titer of virus may be unaccompanied by any lethal or visible pathogenic effects; but with four or five mouse passages the agent becomes lethal in high titer and causes extensive pulmonary consolidation, though its capacity to multiply in the lung has not increased. In one example the adaptation to mouse lung was accompanied by increasing capacity to agglutinate guinea pig red cells without a corresponding increase in agglutinating power for chicken cells. Influenza B virus, in preliminary tests, did not behave in a similar fashion. 2. The adaptation of influenza A virus to mice is accompanied by changes in antigenic pattern, as detected by cross-tests with the agglutination inhibition method. Two strains, initially similar, with passage, changed in pattern along divergent paths so that they became not only unlike the parent strains but unlike each other. This finding has important implications for the interpretation of the strain difference problem in human influenza.

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Incoming Influenza A Virus Evades Early Host Recognition, while Influenza B Virus Induces Interferon Expression Directly upon Entry

Journal of Virology ◽

10.1128/jvi.01050-12 ◽

2012 ◽

Vol 86 (20) ◽

pp. 11183-11193 ◽

Cited By ~ 36

Author(s):

P. Osterlund ◽

M. Strengell ◽

L. P. Sarin ◽

M. M. Poranen ◽

R. Fagerlund ◽

...

Keyword(s):

Influenza A Virus ◽

Influenza A ◽

Host Recognition ◽

Influenza B Virus ◽

Influenza B ◽

B Virus

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Influenza B Virus Causes Milder Pathogenesis and Weaker Inflammatory Responses in Ferrets Than Influenza A Virus

Viral Immunology ◽

10.1089/vim.2009.0045 ◽

2009 ◽

Vol 22 (6) ◽

pp. 423-430 ◽

Cited By ~ 35

Author(s):

Yun Hee Kim ◽

Hyun Soo Kim ◽

Sung Hwan Cho ◽

Sang Heui Seo

Keyword(s):

Influenza A Virus ◽

Influenza A ◽

Inflammatory Responses ◽

Influenza B Virus ◽

Influenza B ◽

B Virus

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The N-Terminal Extension of the Influenza B Virus Nucleoprotein Is Not Required for Nuclear Accumulation or the Expression and Replication of a Model RNA

Journal of Virology ◽

10.1128/jvi.72.6.5307-5312.1998 ◽

1998 ◽

Vol 72 (6) ◽

pp. 5307-5312 ◽

Cited By ~ 25

Author(s):

Mark P. Stevens ◽

Wendy S. Barclay

Keyword(s):

Influenza A Virus ◽

Influenza A ◽

Viral Rna ◽

Nuclear Accumulation ◽

Influenza B Virus ◽

Virus Protein ◽

Influenza B ◽

Coding Region ◽

B Virus ◽

N Terminus

ABSTRACT The nucleoprotein (NP) of influenza B virus is 50 amino acids longer at the N-terminus than influenza A virus NP and lacks homology to the A virus protein over the first 69 residues. We have deleted the N-terminal 51 and 69 residues of the influenza B/Ann Arbor/1/66 virus NP and show that nuclear accumulation of the protein is unaffected. This indicates that the nuclear localization signal is not located at the extreme N terminus, as in influenza A virus NP. To determine if the N-terminal mutants could support the expression and replication of a model influenza B virus RNA, the genes encoding the subunits of the viral RNA-dependent RNA polymerase (PA, PB1, and PB2) were cloned. Coexpression of NP and the P proteins in 293 cells was found to permit the expression and replication of a transfected model RNA based on segment 4 of B/Maryland/59, in which the hemagglutinin-coding region was replaced by a chloramphenicol acetyltransferase gene. The expression and replication of the synthetic RNA were not affected by the replacement of NP with NP mutants lacking the N-terminal 51 or 69 residues, indicating that the N-terminal extension is not required for transcription or replication of the viral RNA. In addition, we report that the influenza B virus NP cannot be functionally replaced by type A virus NP in this system.

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Influenza B viruses exhibit lower within-host diversity than influenza A viruses in human hosts

10.1101/791038 ◽

2019 ◽

Cited By ~ 4

Author(s):

Andrew L. Valesano ◽

William J. Fitzsimmons ◽

John T. McCrone ◽

Joshua G. Petrie ◽

Arnold S. Monto ◽

...

Keyword(s):

Genetic Diversity ◽

Influenza A Virus ◽

Influenza A ◽

Evolutionary Dynamics ◽

Influenza Viruses ◽

Influenza B Virus ◽

Influenza B ◽

Influenza A Viruses ◽

Community Based ◽

B Virus

AbstractInfluenza B virus undergoes seasonal antigenic drift more slowly than influenza A, but the reasons for this difference are unclear. While the evolutionary dynamics of influenza viruses play out globally, they are fundamentally driven by mutation, reassortment, drift, and selection within individual hosts. These processes have recently been described for influenza A virus, but little is known about the evolutionary dynamics of influenza B virus (IBV) at the level of individual infections and transmission events. Here we define the within-host evolutionary dynamics of influenza B virus by sequencing virus populations from naturally-infected individuals enrolled in a prospective, community-based cohort over 8176 person-seasons of observation. Through analysis of high depth-of-coverage sequencing data from samples from 91 individuals with influenza B, we find that influenza B virus accumulates lower genetic diversity than previously observed for influenza A virus during acute infections. Consistent with studies of influenza A viruses, the within-host evolution of influenza B viruses is characterized by purifying selection and the general absence of widespread positive selection of within-host variants. Analysis of shared genetic diversity across 15 sequence-validated transmission pairs suggests that IBV experiences a tight transmission bottleneck similar to that of influenza A virus. These patterns of local-scale evolution are consistent with influenza B virus’ slower global evolutionary rate.ImportanceThe evolution of influenza virus is a significant public health problem and necessitates the annual evaluation of influenza vaccine formulation to keep pace with viral escape from herd immunity. Influenza B virus is a serious health concern for children, in particular, yet remains understudied compared to influenza A virus. Influenza B virus evolves more slowly than influenza A, but the factors underlying this are not completely understood. We studied how the within-host diversity of influenza B virus relates to its global evolution by sequencing viruses from a community-based cohort. We found that influenza B virus populations have lower within-host genetic diversity than influenza A virus and experience a tight genetic bottleneck during transmission. Our work provides insights into the varying dynamics of influenza viruses in human infection.

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Multiplex Real-Time Reverse Transcription PCR for Influenza A Virus, Influenza B Virus, and Severe Acute Respiratory Syndrome Coronavirus 2

Emerging Infectious Diseases ◽

10.3201/eid2707.210462 ◽

2021 ◽

Vol 27 (7) ◽

pp. 1821-1830

Author(s):

Bo Shu ◽

Marie K. Kirby ◽

William G. Davis ◽

Christine Warnes ◽

Jimma Liddell ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Real Time ◽

Influenza A Virus ◽

Reverse Transcription ◽

Influenza A ◽

Influenza B Virus ◽

Influenza B ◽

Reverse Transcription Pcr ◽

B Virus ◽

Virus Influenza

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Detection of some Microorganisms in Patients with Pericarditis by Immunofluresent Assay in Hilla City / Iraq

International Journal of Drug Delivery Technology ◽

10.25258/ijddt.9.2.25 ◽

2019 ◽

Vol 9 (02) ◽

Author(s):

Ilham A Bunyan ◽

Shokry Faaz ◽

Hala H Ali

Keyword(s):

Pericardial Effusion ◽

Influenza A Virus ◽

Teaching Hospital ◽

Influenza A ◽

Culture Media ◽

Hospitalized Patients ◽

Influenza B Virus ◽

Influenza B ◽

Acute Pericarditis ◽

B Virus

In this study, (17) pericardial effusion specimens and blood samples were obtained from hospitalized patients diagnosedwith pericardial effusion at Marjan Teaching Hospital, AL-Sader Teaching Hospital and Ibn-AL-Biatar Cardiovascular Center with age range between (2-77) years old from both sexes, 6(35.30%) male and 11(64.70%) of them were female. The period of collection were extended from July (2018) to January (2019). A total of (17) samples from hospitalized patients with pericardial effusion were included in this study, only 9(52.9%) patients with positive bacterial blood culture media, 7(77.8%) from female and 2(22.2%) from male, and 10(58.8%) patients with positive bacterial pericardial effusion, 7(70%) female and 3(30%) male. In the positive culture group, from 10(58.8%) cases, death occurred in 2(20%) patients, and in the negative culture group, from 7(41.2%) cases, death occurred in 2(38.5%) patients. The sera and pericardium effusion of patients in showed anti-IgM to M. pneumoniae, M. pneumophilia, L. pneumophilia, C. pneumophilia, RSV, Adenovirus, Influenza A virus, and Influenza B virus antibodies. The results showed 7/17(41.2%) positive cases of pericarditis attributed to M. pneumoniae. In (17) patients with acute pericarditis admitted found 2/17(11.8%) positive cases detected by IFA in patients with L. pneumophilia. IFA revealed that 1/17(5.9%) of positive cases for the assay positive for Chlamydophila pneumoniae. Recent study revealed that the IFA detect 2/17 (11.8%) of cases positive for Adenovirus. Depending on IFA recent study identified 2/17(11.8%) cases with RSV associated with another etiological agents and present a case of Influenza A virus infection 1/17(5.9%). Our results showed a case with pericardial effusion positive for Influenza B virus 1/17(5.9%) associated with presence of RSV and L. pneumophilia in patient with intestinal cancer with negative results of bacterial culture media for both pericardial effusion and blood.

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Comparison of the performance of the rapid antigen detection actim Influenza A&B test and RT-PCR in different respiratory specimens

Journal of Medical Microbiology ◽

10.1099/jmm.0.004358-0 ◽

2009 ◽

Vol 58 (3) ◽

pp. 365-370 ◽

Cited By ~ 20

Author(s):

B. Ghebremedhin ◽

I. Engelmann ◽

W. König ◽

B. König

Keyword(s):

Influenza A Virus ◽

Influenza A ◽

Antigen Detection ◽

Influenza B Virus ◽

Influenza B ◽

Rt Pcr ◽

Pcr Assay ◽

B Virus ◽

B Test ◽

Respiratory Specimens

Nowadays, influenza antigen detection test kits are used most frequently to detect influenza A or B virus to establish the diagnosis of influenza rapidly and initiate appropriate therapy. This study was conducted to evaluate the performance of the actim Influenza A&B test (Medix Biochemica). Overall, 473 respiratory specimens were analysed in the actim Influenza A&B test and the results were compared with those from an RT-PCR assay; 461 of these samples originated from paediatric patients aged 7 weeks to 6.5 years either with influenza-related symptoms or from the intensive care unit, and 12 samples originated from adults with underlying lung or haematological diseases. Diagnosis of influenza A or B virus could be established using the actim Influenza A&B test (9/473 samples for influenza A virus and 6/473 for influenza B virus). RT-PCR revealed 23 patients with influenza virus (13/473 for influenza A virus and 10/473 for influenza B virus). The sensitivity and specificity of the actim Influenza A&B test were 65 and 100 % compared with the RT-PCR assay. However, 32 external quality assessment samples containing seven different strains of influenza A subtypes H1N1 and H3N2 and the avian H5N1 were detected correctly by the actim Influenza A&B test. No cross-reactivity to a range of bacterial, fungal and other viral pathogens was observed. In conclusion, the actim Influenza A&B test is reliable for positive results due to its high specificity. Nevertheless, negative results from this test need to be confirmed by a more sensitive assay because of the low sensitivity observed with diagnostic samples.

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