scholarly journals Influenza A Virus Strains Differ in Sensitivity to the Antiviral Action of Mx-GTPase

2008 ◽  
Vol 82 (7) ◽  
pp. 3624-3631 ◽  
Author(s):  
Jan Dittmann ◽  
Silke Stertz ◽  
Daniel Grimm ◽  
John Steel ◽  
Adolfo García-Sastre ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Influenza Viruses ◽  
Host Responses ◽  
Influenza A Viruses ◽  
Species Barrier ◽  
Spanish Flu ◽  
Avian Origin ◽  
Flu Virus ◽  
Virus Strains

ABSTRACT Interferon-mediated host responses are of great importance for controlling influenza A virus infections. It is well established that the interferon-induced Mx proteins possess powerful antiviral activities toward most influenza viruses. Here we analyzed a range of influenza A virus strains for their sensitivities to murine Mx1 and human MxA proteins and found remarkable differences. Virus strains of avian origin were highly sensitive to Mx1, whereas strains of human origin showed much weaker responses. Artificial reassortments of the viral components in a minireplicon system identified the viral nucleoprotein as the main target structure of Mx1. Interestingly, the recently reconstructed 1918 H1N1 “Spanish flu” virus was much less sensitive than the highly pathogenic avian H5N1 strain A/Vietnam/1203/04 when tested in a minireplicon system. Importantly, the human 1918 virus-based minireplicon system was almost insensitive to inhibition by human MxA, whereas the avian influenza A virus H5N1-derived system was well controlled by MxA. These findings suggest that Mx proteins provide a formidable hurdle that hinders influenza A viruses of avian origin from crossing the species barrier to humans. They further imply that the observed insensitivity of the 1918 virus-based replicon to the antiviral activity of human MxA is a hitherto unrecognized characteristic of the “Spanish flu” virus that may contribute to the high virulence of this unusual pandemic strain.

scholarly journals H5N1 Influenza A Virus PB1-F2 Relieves HAX-1-Mediated Restriction of Avian Virus Polymerase PA in Human Lung Cells

2018 ◽  
Vol 92 (11) ◽  
pp. e00425-18 ◽  
Author(s):  
B. Mazel-Sanchez ◽  
I. Boal-Carvalho ◽  
F. Silva ◽  
R. Dijkman ◽  
M. Schmolke
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Influenza Viruses ◽  
Zoonotic Transmission ◽  
Restriction Factor ◽  
Influenza A Viruses ◽  
Human Lung Cells ◽  
Enzymatic Function ◽  
H5n1 Influenza ◽  
Avian Origin

ABSTRACTHighly pathogenic influenza A viruses (IAV) from avian hosts were first reported to directly infect humans 20 years ago. However, such infections are rare events, and our understanding of factors promoting or restricting zoonotic transmission is still limited. One accessory protein of IAV, PB1-F2, was associated with pathogenicity of pandemic and zoonotic IAV. This short (90-amino-acid) peptide does not harbor an enzymatic function. We thus identified host factors interacting with H5N1 PB1-F2, which could explain its importance for virulence. PB1-F2 binds to HCLS1-associated protein X1 (HAX-1), a recently identified host restriction factor of the PA subunit of IAV polymerase complexes. We demonstrate that the PA of a mammal-adapted H1N1 IAV is resistant to HAX-1 imposed restriction, while the PA of an avian-origin H5N1 IAV remains sensitive. We also showed HAX-1 sensitivity for PAs of A/Brevig Mission/1/1918 (H1N1) and A/Shanghai/1/2013 (H7N9), two avian-origin zoonotic IAV. Inhibition of H5N1 polymerase by HAX-1 can be alleviated by its PB1-F2 through direct competition. Accordingly, replication of PB1-F2-deficient H5N1 IAV is attenuated in the presence of large amounts of HAX-1. Mammal-adapted H1N1 and H3N2 viruses do not display this dependence on PB1-F2 for efficient replication in the presence of HAX-1. We propose that PB1-F2 plays a key role in zoonotic transmission of avian H5N1 IAV into humans.IMPORTANCEAquatic and shore birds are the natural reservoir of influenza A viruses from which the virus can jump into a variety of bird and mammal host species, including humans. H5N1 influenza viruses are a good model for this process. They pose an ongoing threat to human and animal health due to their high mortality rates. However, it is currently unclear what restricts these interspecies jumps on the host side or what promotes them on the virus side. Here we show that a short viral peptide, PB1-F2, helps H5N1 bird influenza viruses to overcome a human restriction factor of the viral polymerase complex HAX-1. Interestingly, we found that human influenza A virus polymerase complexes are already adapted to HAX-1 and do not require this function of PB1-F2. We thus propose that a functional full-length PB1-F2 supports direct transmission of bird viruses into humans.

scholarly journals Isolation and Characterization of a Distinct Influenza A Virus from Egyptian Bats

2018 ◽  
Vol 93 (2) ◽  
Author(s):  
Ahmed Kandeil ◽  
Mokhtar R. Gomaa ◽  
Mahmoud M. Shehata ◽  
Ahmed N. El Taweel ◽  
Sara H. Mahmoud ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Mdck Cells ◽  
Genomic Analysis ◽  
Cross Reactivity ◽  
Influenza Viruses ◽  
Avian Host ◽  
Influenza A Viruses ◽  
Species Barrier ◽  
Isolation And Characterization

ABSTRACT Recently, two genetically distinct influenza viruses were detected in bats in Guatemala and Peru. We conducted influenza A virus surveillance among four bat species in Egypt. Out of 1,202 swab specimens, 105 were positive by real-time PCR. A virus was successfully isolated in eggs and propagated in MDCK cells in the presence of N-tosyl-l-phenylalanine chloromethyl ketone-treated trypsin. Genomic analysis revealed that the virus was phylogenetically distinct from all other influenza A viruses. Analysis of the hemagglutinin gene suggested a common ancestry with other H9 viruses, and the virus showed a low level of cross-reactivity with serum raised against H9N2 viruses. Bats were seropositive for the isolated viruses. The virus replicated in the lungs of experimentally infected mice. While it is genetically distinct, this virus shares several avian influenza virus characteristics suggesting a more recent avian host origin. IMPORTANCE Through surveillance, we isolated and characterized an influenza A virus from Egyptian fruit bats. This virus had an affinity to avian-like receptors but was also able to infect mice. Our findings indicate that bats may harbor a diversity of influenza A viruses. Such viruses may have the potential to cross the species barrier to infect other species, including domestic birds, mammals, and, possibly, humans.

scholarly journals Unseasonal Transmission of H3N2 Influenza A Virus During the Swine-Origin H1N1 Pandemic

2010 ◽  
Vol 84 (11) ◽  
pp. 5715-5718 ◽  
Author(s):  
Elodie Ghedin ◽  
David E. Wentworth ◽  
Rebecca A. Halpin ◽  
Xudong Lin ◽  
Jayati Bera ◽  
...  
Keyword(s):  
New York ◽  
Influenza A Virus ◽  
Influenza A ◽  
New York State ◽  
The United States ◽  
Influenza Viruses ◽  
Influenza A Viruses ◽  
York State ◽  
Low Incidence ◽  
H3n2 Influenza

ABSTRACT The initial wave of swine-origin influenza A virus (pandemic H1N1/09) in the United States during the spring and summer of 2009 also resulted in an increased vigilance and sampling of seasonal influenza viruses (H1N1 and H3N2), even though they are normally characterized by very low incidence outside of the winter months. To explore the nature of virus evolution during this influenza “off-season,” we conducted a phylogenetic analysis of H1N1 and H3N2 sequences sampled during April to June 2009 in New York State. Our analysis revealed that multiple lineages of both viruses were introduced and cocirculated during this time, as is typical of influenza virus during the winter. Strikingly, however, we also found strong evidence for the presence of a large transmission chain of H3N2 viruses centered on the south-east of New York State and which continued until at least 1 June 2009. These results suggest that the unseasonal transmission of influenza A viruses may be more widespread than is usually supposed.

scholarly journals Influenza A Virus Inhibits RSV Infection via a Two-Wave Expression of IFIT Proteins

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1171
Author(s):  
Yaron Drori ◽  
Jasmine Jacob-Hirsch ◽  
Rakefet Pando ◽  
Aharona Glatman-Freedman ◽  
Nehemya Friedman ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Influenza Viruses ◽  
Mass Spectrometry Analysis ◽  
Influenza A Viruses ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Mouse Lungs

Influenza viruses and respiratory syncytial virus (RSV) are respiratory viruses that primarily circulate worldwide during the autumn and winter seasons. Seasonal surveillance has shown that RSV infection generally precedes influenza. However, in the last four winter seasons (2016–2020) an overlap of the morbidity peaks of both viruses was observed in Israel, and was paralleled by significantly lower RSV infection rates. To investigate whether the influenza A virus inhibits RSV, human cervical carcinoma (HEp2) cells or mice were co-infected with influenza A and RSV. Influenza A inhibited RSV growth, both in vitro and in vivo. Mass spectrometry analysis of mouse lungs infected with influenza A identified a two-wave pattern of protein expression upregulation, which included members of the interferon-induced protein with the tetratricopeptide (IFITs) family. Interestingly, in the second wave, influenza A viruses were no longer detectable in mouse lungs. In addition, knockdown and overexpression of IFITs in HEp2 cells affected RSV multiplicity. In conclusion, influenza A infection inhibits RSV infectivity via upregulation of IFIT proteins in a two-wave modality. Understanding the immune system involvement in the interaction between influenza A and RSV viruses will contribute to the development of future treatment strategies against these viruses.

IFN-κ suppresses the replication of influenza A viruses through the IFNAR-MAPK-Fos-CHD6 axis

2020 ◽  
Vol 13 (626) ◽  
pp. eaaz3381 ◽  
Author(s):  
Yongquan He ◽  
Weihui Fu ◽  
Kangli Cao ◽  
Qian He ◽  
Xiangqing Ding ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Influenza Viruses ◽  
Mitogen Activated Protein Kinase ◽  
Type I Interferons ◽  
Type I ◽  
Influenza A Viruses ◽  
Human Lung Cells ◽  
Avian Influenza A Virus ◽  
Factor C

Type I interferons (IFNs) are the first line of defense against viral infection. Using a mouse model of influenza A virus infection, we found that IFN-κ was one of the earliest responding type I IFNs after infection with H9N2, a low-pathogenic avian influenza A virus, whereas this early induction did not occur upon infection with the epidemic-causing H7N9 virus. IFN-κ efficiently suppressed the replication of various influenza viruses in cultured human lung cells, and chromodomain helicase DNA binding protein 6 (CHD6) was the major effector for the antiviral activity of IFN-κ, but not for that of IFN-α or IFN-β. The induction of CHD6 required both of the type I IFN receptor subunits IFNAR1 and IFNAR2, the mitogen-activated protein kinase (MAPK) p38, and the transcription factor c-Fos but was independent of signal transducer and activator of transcription 1 (STAT1) activity. In addition, we showed that pretreatment with IFN-κ protected mice from lethal influenza viral challenge. Together, our findings identify an IFN-κ–specific pathway that constrains influenza A virus and provide evidence that IFN-κ may have potential as a preventative and therapeutic agent against influenza A virus.

scholarly journals VirPreNet: A weighted ensemble convolutional neural network for the virulence prediction of influenza A virus using all 8 segments

2020 ◽  
Author(s):  
Rui Yin ◽  
Zihan Luo ◽  
Pei Zhuang ◽  
Zhuoyi Lin ◽  
Chee Keong Kwoh
Keyword(s):  
Public Health ◽  
Neural Network ◽  
Convolutional Neural Network ◽  
Influenza A Virus ◽  
Influenza A ◽  
Lethal Dose ◽  
Influenza Viruses ◽  
Numerical Representation ◽  
Influenza A Viruses ◽  
Linear Layer

AbstractMotivationInfluenza viruses are persistently threatening public health, causing annual epidemics and sporadic pandemics. The evolution of influenza viruses remains to be the main obstacle in the effectiveness of antiviral treatments due to rapid mutations. Previous work has been investigated to reveal the determinants of virulence of the influenza A virus. To further facilitate flu surveillance, explicit detection of influenza virulence is crucial to protect public health from potential future pandemics.ResultsIn this paper, we propose a weighted ensemble convolutional neural network for the virulence prediction of influenza A viruses named VirPreNet that uses all 8 segments. Firstly, mouse lethal dose 50 is exerted to label the virulence of infections into two classes, namely avirulent and virulent. A numerical representation of amino acids named ProtVec is applied to the 8-segments in a distributed manner to encode the biological sequences. After splittings and embeddings of influenza strains, the ensemble convolutional neural network is constructed as the base model on the influenza dataset of each segment, which serves as the VirPreNet’s main part. Followed by a linear layer, the initial predictive outcomes are integrated and assigned with different weights for the final prediction. The experimental results on the collected influenza dataset indicate that VirPreNet achieves state-of-the-art performance combining ProtVec with our proposed architecture. It outperforms baseline methods on the independent testing data. Moreover, our proposed model reveals the importance of PB2 and HA segments on the virulence prediction. We believe that our model may provide new insights into the investigation of influenza [email protected] and ImplementationCodes and data to generate the VirPreNet are publicly available at https://github.com/Rayin-saber/VirPreNet

scholarly journals Efficient whole genome sequencing of influenza A viruses

2019 ◽  
Author(s):  
Marina Escalera-Zamudio ◽  
Ana Georgina Cobián-Güemes ◽  
Blanca Taboada ◽  
Irma López-Martínez ◽  
Joel Armando Vázquez-Pérez ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Influenza A Virus ◽  
Genome Sequencing ◽  
Influenza A ◽  
Genetic Material ◽  
Influenza Viruses ◽  
Epidemiological Surveillance ◽  
Clinical Samples ◽  
Whole Genome ◽  
Influenza A Viruses

ABSTRACTThe constant threat of emergence for novel pathogenic influenza A viruses with pandemic potential, makes full-genome characterization of circulating influenza viral strains a high priority, allowing detection of novel and re-assorting variants. Sequencing the full-length genome of influenza A virus traditionally required multiple amplification rounds, followed by the subsequent sequencing of individual PCR products. The introduction of high-throughput sequencing technologies has made whole genome sequencing easier and faster. We present a simple protocol to obtain whole genome sequences of hypothetically any influenza A virus, even with low quantities of starting genetic material. The complete genomes of influenza A viruses of different subtypes and from distinct sources (clinical samples of pdmH1N1, tissue culture-adapted H3N2 viruses, or avian influenza viruses from cloacal swabs) were amplified with a single multisegment reverse transcription-PCR reaction and sequenced using Illumina sequencing platform. Samples with low quantity of genetic material after initial PCR amplification were re-amplified by an additional PCR using random primers. Whole genome sequencing was successful for 66% of the samples, whilst the most relevant genome segments for epidemiological surveillance (corresponding to the hemagglutinin and neuraminidase) were sequenced with at least 93% coverage (and a minimum 10x) for 98% of the samples. Low coverage for some samples is likely due to an initial low viral RNA concentration in the original sample. The proposed methodology is especially suitable for sequencing a large number of samples, when genetic data is urgently required for strains characterization, and may also be useful for variant analysis.

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

2019 ◽  
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.

scholarly journals Independence of Evolutionary and Mutational Rates after Transmission of Avian Influenza Viruses to Swine

1999 ◽  
Vol 73 (3) ◽  
pp. 1878-1884 ◽  
Author(s):  
J. Stech ◽  
X. Xiong ◽  
C. Scholtissek ◽  
R. G. Webster
Keyword(s):  
New York ◽  
Avian Influenza ◽  
Influenza A ◽  
Swine Influenza ◽  
Influenza Viruses ◽  
Mutation Rates ◽  
Influenza A Viruses ◽  
Species Barrier ◽  
H1n1 Strain ◽  
Serologic Evidence

ABSTRACT In 1979, an H1N1 avian influenza virus crossed the species barrier, establishing a new lineage in European swine. Because there is no direct or serologic evidence of previous H1N1 strains in these pigs, these isolates provide a model for studying early evolution of influenza viruses. The evolutionary rates of both the coding and noncoding changes of the H1N1 swine strains are higher than those of human and classic swine influenza A viruses. In addition, early H1N1 swine isolates show a marked plaque heterogeneity that consistently appears after a few passages. The presence of a mutator mutation was postulated (C. Scholtissek, S. Ludwig, and W. M. Fitch, Arch. Virol. 131:237–250, 1993) to account for these observations and the successful establishment of an avian H1N1 strain in swine. To address this question, we calculated the mutation rates of A/Mallard/New York/6750/78 (H2N2) and A/Swine/Germany/2/81 (H1N1) by using the frequency of amantadine-resistant mutants. To account for the inherent variability of estimated mutation rates, we used a probabilistic model for the statistical analysis. The resulting estimated mutation rates of the two strains were not significantly different. Therefore, an increased mutation rate due to the presence of a mutator mutation is unlikely to have led to the successful introduction of avian H1N1 viruses in European swine.

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