scholarly journals A Non-phylogeny-dependent Reassortment Detection Method for Influenza A Viruses

2021 ◽  
Vol 1 ◽  
Author(s):  
Xingfei Gong ◽  
Mingda Hu ◽  
Boqian Wang ◽  
Haoyi Yang ◽  
Yuan Jin ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Detection Method ◽  
Rna Virus ◽  
Self Organizing Map ◽  
Influenza A Viruses ◽  
Multiple Sequence ◽  
Distance Methods ◽  
Virus Reassortment ◽  
Pandemic Strains

Influenza A virus is a segmented RNA virus whose genome consists of 8 single-stranded negative-sense RNA segments. This unique genetic structure allows viruses to exchange their segments through reassortment when they infect the same host cell. Studying the determination and nature of influenza A virus reassortment is critical to understanding the generation of pandemic strains and the spread of viruses across species. Reassortment detection is the first step in influenza A virus reassortment research. Several methods for automatic detection of reassortment have been proposed, which can be roughly divided into two categories: phylogenetic methods and distance methods. In this article, we proposed a reassortment detection method that does not require multiple sequence alignment and phylogenetic analysis. We extracted the codon features from the segment sequence and expressed the sequence as a feature vector, and then used the clustering method of self-organizing map to cluster the sequence for each segment. Based on the clustering results and the epidemiological information of the virus, the reassortment detection was implemented. We used this method to perform reassortment detection on the collected 7,075 strains from Asia and identified 516 reassortment events. We also conducted a statistical analysis of the identified reassortment events and found conclusions consistent with previous studies. Our method will provide new insights for automating reassortment detection tasks and understanding the reassortment patterns of influenza A viruses.

UBIQUITOUS REASSORTMENTS IN INFLUENZA A VIRUSES

2008 ◽  
Vol 06 (05) ◽  
pp. 981-999 ◽  
Author(s):  
XIU-FENG WAN ◽  
MUFIT OZDEN ◽  
GUOHUI LIN
Keyword(s):  
Influenza A ◽  
Matrix Protein ◽  
Minimum Spanning Tree ◽  
Migratory Birds ◽  
Rna Virus ◽  
Influenza Pandemic ◽  
Influenza Viruses ◽  
Influenza A Viruses ◽  
H5n1 Avian Influenza Virus ◽  
Pandemic Strains

The influenza A virus is a negative-stranded RNA virus composed of eight segmented RNA molecules, including polymerases (PB2, PB1, PA), hemagglutinin (HA), nucleoprotein (NP), neuraminidase (NA), matrix protein (MP), and nonstructure gene (NS). The influenza A viruses are notorious for rapid mutations, frequent reassortments, and possible recombinations. Among these evolutionary events, reassortments refer to exchanges of discrete RNA segments between co-infected influenza viruses, and they have facilitated the generation of pandemic and epidemic strains. Thus, identification of reassortments will be critical for pandemic and epidemic prevention and control. This paper presents a reassortment identification method based on distance measurement using complete composition vector (CCV) and segment clustering using a minimum spanning tree (MST) algorithm. By applying this method, we identified 34 potential reassortment clusters among 2,641 PB2 segments of influenza A viruses. Among the 83 serotypes tested, at least 56 (67.46%) exchanged their fragments with another serotype of influenza A viruses. These identified reassortments involve 1,957 H2N1 and 1,968 H3N2 influenza pandemic strains as well as H5N1 avian influenza virus isolates, which have generated the potential for a future pandemic threat. More frequent reassortments were found to occur in wild birds, especially migratory birds. This MST clustering program is written in Java and will be available upon request.

scholarly journals Zinc-embedded fabrics inactivate SARS-CoV-2 and influenza A virus

2020 ◽  
Author(s):  
Vikram Gopal ◽  
Benjamin E. Nilsson-Payant ◽  
Hollie French ◽  
Jurre Y. Siegers ◽  
Wai-shing Yung ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Rna Virus ◽  
Zinc Content ◽  
Respiratory Viruses ◽  
Zinc Ions ◽  
Liquid Droplets ◽  
Influenza A Viruses ◽  
Wide Range ◽  
Polyamide 6.6

AbstractInfections with respiratory viruses can spread via liquid droplets and aerosols, and cause diseases such as influenza and COVID-19. Face masks and other personal protective equipment (PPE) can act as barriers that prevent the spread of respiratory droplets containing these viruses. However, influenza A viruses and coronaviruses are stable for hours on various materials, which makes frequent and correct disposal of these PPE important. Metal ions embedded into PPE may inactivate respiratory viruses, but confounding factors such as absorption of viruses make measuring and optimizing the inactivation characteristics difficult. Here we used polyamide 6.6 (PA66) fibers that had zinc ions embedded during the polymerisation process and systematically investigated if these fibers can absorb and inactivate pandemic SARS-CoV-2 and influenza A virus H1N1. We find that these viruses are readily absorbed by PA66 fabrics and inactivated by zinc ions embedded into this fabric. The inactivation rate (pfu·gram−1·min−1) exceeds the number of active virus particles expelled by a cough and supports a wide range of viral loads. Moreover, we found that the zinc content and the virus inactivating property of the fabric remain stable over 50 standardized washes. Overall, these results provide new insight into the development of “pathogen-free” PPE and better protection against RNA virus spread.

scholarly journals Heterologous Packaging Signals on Segment 4, but Not Segment 6 or Segment 8, Limit Influenza A Virus Reassortment

2017 ◽  
Vol 91 (11) ◽  
Author(s):  
Maria C. White ◽  
John Steel ◽  
Anice C. Lowen
Keyword(s):  
Public Health ◽  
Influenza A Virus ◽  
Influenza A ◽  
Influenza A Viruses ◽  
Packaging Signal ◽  
Significant Preference ◽  
Virus Reassortment ◽  
Segment 8 ◽  
The Impact ◽  
Packaging Signals

ABSTRACT Influenza A virus (IAV) RNA packaging signals serve to direct the incorporation of IAV gene segments into virus particles, and this process is thought to be mediated by segment-segment interactions. These packaging signals are segment and strain specific, and as such, they have the potential to impact reassortment outcomes between different IAV strains. Our study aimed to quantify the impact of packaging signal mismatch on IAV reassortment using the human seasonal influenza A/Panama/2007/99 (H3N2) and pandemic influenza A/Netherlands/602/2009 (H1N1) viruses. Focusing on the three most divergent segments, we constructed pairs of viruses that encoded identical proteins but differed in the packaging signal regions on a single segment. We then evaluated the frequency with which segments carrying homologous versus heterologous packaging signals were incorporated into reassortant progeny viruses. We found that, when segment 4 (HA) of coinfecting parental viruses was modified, there was a significant preference for the segment containing matched packaging signals relative to the background of the virus. This preference was apparent even when the homologous HA constituted a minority of the HA segment population available in the cell for packaging. Conversely, when segment 6 (NA) or segment 8 (NS) carried modified packaging signals, there was no significant preference for homologous packaging signals. These data suggest that movement of NA and NS segments between the human H3N2 and H1N1 lineages is unlikely to be restricted by packaging signal mismatch, while movement of the HA segment would be more constrained. Our results indicate that the importance of packaging signals in IAV reassortment is segment dependent. IMPORTANCE Influenza A viruses (IAVs) can exchange genes through reassortment. This process contributes to both the highly diverse population of IAVs found in nature and the formation of novel epidemic and pandemic IAV strains. Our study sought to determine the extent to which IAV packaging signal divergence impacts reassortment between seasonal IAVs. Our knowledge in this area is lacking, and insight into the factors that influence IAV reassortment will inform and strengthen ongoing public health efforts to anticipate the emergence of new viruses. We found that the packaging signals on the HA segment, but not the NA or NS segments, restricted IAV reassortment. Thus, the packaging signals of the HA segment could be an important factor in determining the likelihood that two IAV strains of public health interest will undergo reassortment.

scholarly journals Enisamium is a small molecule inhibitor of the influenza A virus and SARS-CoV-2 RNA polymerases

2020 ◽  
Author(s):  
Alexander P Walker ◽  
Haitian Fan ◽  
Jeremy R Keown ◽  
Victor Margitich ◽  
Jonathan M Grimes ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Influenza A Virus ◽  
Small Molecule ◽  
Broad Spectrum ◽  
Influenza A ◽  
Rna Synthesis ◽  
Rna Virus ◽  
Rna Polymerases ◽  
Influenza A Viruses ◽  
Molecule Inhibitor

AbstractInfluenza A virus and coronavirus strains cause a mild to severe respiratory disease that can result in death. Although vaccines exist against circulating influenza A viruses, such vaccines are ineffective against emerging pandemic influenza A viruses. Currently, no vaccine exists against coronavirus infections, including pandemic SARS-CoV-2, the causative agent of the Coronavirus Disease 2019 (COVID-19). To combat these RNA virus infections, alternative antiviral strategies are needed. A key drug target is the viral RNA polymerase, which is responsible for viral RNA synthesis. In January 2020, the World Health Organisation identified enisamium as a candidate therapeutic against SARS-CoV-2. Enisamium is an isonicotinic acid derivative that is an inhibitor of multiple influenza B and A virus strains in cell culture and clinically approved in 11 countries. Here we show using in vitro assays that enisamium and its putative metabolite, VR17-04, inhibit the activity of the influenza virus and the SARS-CoV-2 RNA polymerase. VR17-04 displays similar efficacy against the SARS-CoV-2 RNA polymerase as the nucleotide analogue remdesivir triphosphate. These results suggest that enisamium is a broad-spectrum small molecule inhibitor of RNA virus RNA synthesis, and implicate it as a possible therapeutic option for treating SARS-CoV-2 infection. Unlike remdesivir, enisamium does not require intravenous administration which may be advantageous for the development of COVID-19 treatments outside a hospital setting.ImportanceInfluenza A virus and SARS-CoV-2 are respiratory viruses capable of causing pandemics, and the latter is responsible for the Coronavirus Disease 2019 (COVID-19) pandemic. Both viruses encode RNA polymerases which transcribe their RNA genomes and are important targets for antiviral drugs including remdesivir. Here, we show that the antiviral drug enisamium inhibits the RNA polymerases of both influenza A virus and SARS-CoV-2. Furthermore, we show that a putative metabolite of enisamium is a more potent inhibitor, inhibiting the SARS-CoV-2 RNA polymerase with similar efficiency to remdesivir. Our data offer insight into the mechanism of action for enisamium, and implicate it as a broad-spectrum antiviral which could be used in the treatment of SARS-CoV-2 infection.

scholarly journals Investigating Influenza A Virus Infection: Tools To Track Infection and Limit Tropism: TABLE 1

2015 ◽  
Vol 89 (12) ◽  
pp. 6167-6170 ◽  
Author(s):  
Jessica K. Fiege ◽  
Ryan A. Langlois
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Therapeutic Interventions ◽  
Microrna Target ◽  
Influenza A Viruses ◽  
Host Interactions ◽  
Target Sites ◽  
Recent Developments ◽  
Cellular Tropism ◽  
The Relationship

Influenza A viruses display a broad cellular tropism within the respiratory tracts of mammalian hosts. Uncovering the relationship between tropism and virus immunity, pathogenesis, and transmission will be critical for the development of therapeutic interventions. Here we discuss recent developments of several recombinant strains of influenza A virus. These viruses have inserted reporters to track tropism, microRNA target sites to restrict tropism, or barcodes to assess transmission dynamics, expanding our understanding of pathogen-host interactions.

scholarly journals Unexpected Functional Divergence of Bat Influenza Virus NS1 Proteins

2017 ◽  
Vol 92 (5) ◽  
Author(s):  
Hannah L. Turkington ◽  
Mindaugas Juozapaitis ◽  
Nikos Tsolakos ◽  
Eugenia Corrales-Aguilar ◽  
Martin Schwemmle ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Virulence Factor ◽  
Influenza A ◽  
Nonstructural Protein ◽  
Functional Divergence ◽  
Protein A ◽  
Regulatory Subunit ◽  
Ns1 Protein ◽  
Influenza A Viruses ◽  
Hydrophobic Patch

ABSTRACT Recently, two influenza A virus (FLUAV) genomes were identified in Central and South American bats. These sequences exhibit notable divergence from classical FLUAV counterparts, and functionally, bat FLUAV glycoproteins lack canonical receptor binding and destroying activity. Nevertheless, other features that distinguish these viruses from classical FLUAVs have yet to be explored. Here, we studied the viral nonstructural protein NS1, a virulence factor that modulates host signaling to promote efficient propagation. Like all FLUAV NS1 proteins, bat FLUAV NS1s bind double-stranded RNA and act as interferon antagonists. Unexpectedly, we found that bat FLUAV NS1s are unique in being unable to bind host p85β, a regulatory subunit of the cellular metabolism-regulating enzyme, phosphoinositide 3-kinase (PI3K). Furthermore, neither bat FLUAV NS1 alone nor infection with a chimeric bat FLUAV efficiently activates Akt, a PI3K effector. Structure-guided mutagenesis revealed that the bat FLUAV NS1-p85β interaction can be reengineered (in a strain-specific manner) by changing two to four NS1 residues (96L, 99M, 100I, and 145T), thereby creating a hydrophobic patch. Notably, ameliorated p85β-binding is insufficient for bat FLUAV NS1 to activate PI3K, and a chimeric bat FLUAV expressing NS1 with engineered hydrophobic patch mutations exhibits cell-type-dependent, but species-independent, propagation phenotypes. We hypothesize that bat FLUAV hijacking of PI3K in the natural bat host has been selected against, perhaps because genes in this metabolic pathway were differentially shaped by evolution to suit the unique energy use strategies of this flying mammal. These data expand our understanding of the enigmatic functional divergence between bat FLUAVs and classical mammalian and avian FLUAVs. IMPORTANCE The potential for novel influenza A viruses to establish infections in humans from animals is a source of continuous concern due to possible severe outbreaks or pandemics. The recent discovery of influenza A-like viruses in bats has raised questions over whether these entities could be a threat to humans. Understanding unique properties of the newly described bat influenza A-like viruses, such as their mechanisms to infect cells or how they manipulate host functions, is critical to assess their likelihood of causing disease. Here, we characterized the bat influenza A-like virus NS1 protein, a key virulence factor, and found unexpected functional divergence of this protein from counterparts in other influenza A viruses. Our study dissects the molecular changes required by bat influenza A-like virus NS1 to adopt classical influenza A virus properties and suggests consequences of bat influenza A-like virus infection, potential future evolutionary trajectories, and intriguing virus-host biology in bat species.

scholarly journals Characterization of a Human H5N1 Influenza A Virus Isolated in 2003

2005 ◽  
Vol 79 (15) ◽  
pp. 9926-9932 ◽  
Author(s):  
Kyoko Shinya ◽  
Masato Hatta ◽  
Shinya Yamada ◽  
Ayato Takada ◽  
Shinji Watanabe ◽  
...  
Keyword(s):  
Hong Kong ◽  
Avian Influenza ◽  
Influenza A Virus ◽  
Influenza A ◽  
Mainland China ◽  
Virus Infections ◽  
Influenza A Viruses ◽  
H5n1 Avian Influenza Virus ◽  
H5n1 Influenza ◽  
Avian Influenza A Virus

ABSTRACT In 2003, H5N1 avian influenza virus infections were diagnosed in two Hong Kong residents who had visited the Fujian province in mainland China, affording us the opportunity to characterize one of the viral isolates, A/Hong Kong/213/03 (HK213; H5N1). In contrast to H5N1 viruses isolated from humans during the 1997 outbreak in Hong Kong, HK213 retained several features of aquatic bird viruses, including the lack of a deletion in the neuraminidase stalk and the absence of additional oligosaccharide chains at the globular head of the hemagglutinin molecule. It demonstrated weak pathogenicity in mice and ferrets but caused lethal infection in chickens. The original isolate failed to produce disease in ducks but became more pathogenic after five passages. Taken together, these findings portray the HK213 isolate as an aquatic avian influenza A virus without the molecular changes associated with the replication of H5N1 avian viruses in land-based poultry such as chickens. This case challenges the view that adaptation to land-based poultry is a prerequisite for the replication of aquatic avian influenza A viruses in humans.

Influenza type A virus M protein expression on infected cells is responsible for cross-reactive recognition by cytotoxic thymus-derived lymphocytes

1980 ◽  
Vol 29 (2) ◽  
pp. 719-723 ◽  
Author(s):  
C S Reiss ◽  
J L Schulman
Keyword(s):  
T Cell ◽  
Influenza A Virus ◽  
Influenza A ◽  
Rabbit Antiserum ◽  
Type A ◽  
M Protein ◽  
Cytotoxic T Cell ◽  
Influenza A Viruses ◽  
Infected Cells ◽  
Cytotoxic T Cell Responses

M protein of influenza A virus was detected with rabbit antiserum by both indirect immunofluorescence and by antibody plus complement-mediated cytolysis on the cell surfaces of both productively and nonproductively infected cells. In contrast, antiserum to nucleoprotein failed to react with unfixed infected cells, but did bind to fixed infected cells, especially in the perinuclear area. Incorporation of antiserum to M protein in a T-cell-mediated cytotoxicity assay produced almost complete abrogation of lysis of H-2-compatible cells infected with an influenza A virus of a subtype which differed from that used to elicit the cytotoxic T cells. However, the antibody did not significantly block 51Cr release from cells infected with the homotypic type A influenza virus. These observations are in accord with the hypothesis that the cross-reactive cytotoxic T-cell responses seen with cells infected by heterotypic influenza A viruses are due to recognition of a common M protein.

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.

Sign in / Sign up

Export Citation Format

Share Document