scholarly journals Analysis of the Genetic Diversity Associated With the Drug Resistance and Pathogenicity of Influenza A Virus Isolated in Bangladesh From 2002 to 2019

2021 ◽  
Vol 12 ◽  
Author(s):  
Md. Golzar Hossain ◽  
Sharmin Akter ◽  
Priya Dhole ◽  
Sukumar Saha ◽  
Taheruzzaman Kazi ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Drug Resistance ◽  
Influenza A Virus ◽  
Influenza A ◽  
Neuraminidase Inhibitor ◽  
Avian Species ◽  
Lower Prevalence ◽  
Bioinformatic Tools ◽  
Wide Range ◽  
And Control

The subtype prevalence, drug resistance- and pathogenicity-associated mutations, and the distribution of the influenza A virus (IAV) isolates identified in Bangladesh from 2002 to 2019 were analyzed using bioinformatic tools. A total of 30 IAV subtypes have been identified in humans (4), avian species (29), and environment (5) in Bangladesh. The predominant subtypes in human and avian species are H1N1/H3N2 and H5N1/H9N2, respectively. However, the subtypes H5N1/H9N2 infecting humans and H3N2/H1N1 infecting avian species have also been identified. Among the avian species, the maximum number of subtypes (27) have been identified in ducks. A 3.56% of the isolates showed neuraminidase inhibitor (NAI) resistance with a prevalence of 8.50, 1.33, and 2.67% in avian species, humans, and the environment, respectively, the following mutations were detected: V116A, I117V, D198N, I223R, S247N, H275Y, and N295S. Prevalence of adamantane-resistant IAVs was 100, 50, and 30.54% in humans, the environment, and avian species, respectively, the subtypes H3N2, H1N1, H9N2, and H5N2 were highly prevalent, with the subtype H5N1 showing a comparatively lower prevalence. Important PB2 mutations such D9N, K526R, A588V, A588I, G590S, Q591R, E627K, K702R, and S714R were identified. A wide range of IAV subtypes have been identified in Bangladesh with a diversified genetic variation in the NA, M2, and PB2 proteins providing drug resistance and enhanced pathogenicity. This study provides a detailed analysis of the subtypes, and the host range of the IAV isolates and the genetic variations related to their proteins, which may aid in the prevention, treatment, and control of IAV infections in Bangladesh, and would serve as a basis for future investigations.

scholarly journals A System Based-Approach to Examine Host Response during Infection with Influenza A Virus Subtype H7N9 in Human and Avian Cells

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 448
Author(s):  
Biruhalem Taye ◽  
Hui Chen ◽  
Dawn Su-Yin Yeo ◽  
Shirley Gek-Kheng Seah ◽  
Michelle Su-Yen Wong ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Host Response ◽  
Influenza A ◽  
Severe Disease ◽  
Airway Epithelial Cells ◽  
Vital Role ◽  
Avian Species ◽  
Hippo Signaling ◽  
H7n9 Virus ◽  
Bioinformatic Tools

Although the influenza A virus H7N9 subtype circulates within several avian species, it can also infect humans with a severe disease outcome. To better understand the biology of the H7N9 virus we examined the host response to infection in avian and human cells. In this study we used the A/Anhui/1/2013 strain, which was isolated during the first wave of the H7N9 epidemic. The H7N9 virus-infected both human (Airway Epithelial cells) and avian (Chick Embryo Fibroblast) cells, and each infected host transcriptome was examined with bioinformatic tools and compared with other representative avian and human influenza A virus subtypes. The H7N9 virus induced higher expression changes (differentially regulated genes) in both cell lines, with more prominent changes observed in avian cells. Ortholog mapping of differentially expression genes identified significant enriched common and cell-type pathways during H7N9 infections. This data confirmed our previous findings that different influenza A virus subtypes have virus-specific replication characteristics and anti-virus signaling in human and avian cells. In addition, we reported for the first time, the new HIPPO signaling pathway in avian cells, which we hypothesized to play a vital role to maintain the antiviral state of H7N9 virus-infected avian cells. This could explain the absence of disease symptoms in avian species that tested positive for the presence of H7N9 virus.

scholarly journals Epistatic Interactions within the Influenza A Virus Polymerase Complex Mediate Mutagen Resistance and Replication Fidelity

mSphere ◽  
2017 ◽  
Vol 2 (4) ◽  
Author(s):  
Matthew D. Pauly ◽  
Daniel M. Lyons ◽  
William J. Fitzsimmons ◽  
Adam S. Lauring
Keyword(s):  
Genetic Diversity ◽  
Drug Resistance ◽  
Influenza Virus ◽  
Influenza A Virus ◽  
Mutation Rate ◽  
Influenza A ◽  
Rna Viruses ◽  
Nucleoside Analogs ◽  
Mutation Rates ◽  
Polymerase Complex

ABSTRACT RNA viruses exist as genetically diverse populations. This standing genetic diversity gives them the potential to adapt rapidly, evolve resistance to antiviral therapeutics, and evade immune responses. Viral mutants with altered mutation rates or mutational tolerance have provided insights into how genetic diversity arises and how it affects the behavior of RNA viruses. To this end, we identified variants within the polymerase complex of influenza virus that are able tolerate drug-mediated increases in viral mutation rates. We find that drug resistance is highly dependent on interactions among mutations in the polymerase complex. In contrast to other viruses, influenza virus counters the effect of higher mutation rates primarily by maintaining high levels of genome replication. These findings suggest the importance of maintaining large population sizes for viruses with high mutation rates and show that multiple proteins can affect both mutation rate and genome synthesis. Lethal mutagenesis is a broad-spectrum antiviral strategy that employs mutagenic nucleoside analogs to exploit the high mutation rate and low mutational tolerance of many RNA viruses. Studies of mutagen-resistant viruses have identified determinants of replicative fidelity and the importance of mutation rate to viral population dynamics. We have previously demonstrated the effective lethal mutagenesis of influenza A virus using three nucleoside analogs as well as the virus’s high genetic barrier to mutagen resistance. Here, we investigate the mutagen-resistant phenotypes of mutations that were enriched in drug-treated populations. We find that PB1 T123A has higher replicative fitness than the wild type, PR8, and maintains its level of genome production during 5-fluorouracil (2,4-dihydroxy-5-fluoropyrimidine) treatment. Surprisingly, this mutagen-resistant variant also has an increased baseline rate of C-to-U and G-to-A mutations. A second drug-selected mutation, PA T97I, interacts epistatically with PB1 T123A to mediate high-level mutagen resistance, predominantly by limiting the inhibitory effect of nucleosides on polymerase activity. Consistent with the importance of epistatic interactions in the influenza virus polymerase, our data suggest that nucleoside analog resistance and replication fidelity are strain dependent. Two previously identified ribavirin {1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1H-1,2,4-triazole-3-carboxamide} resistance mutations, PB1 V43I and PB1 D27N, do not confer drug resistance in the PR8 background, and the PR8-PB1 V43I polymerase exhibits a normal baseline mutation rate. Our results highlight the genetic complexity of the influenza A virus polymerase and demonstrate that increased replicative capacity is a mechanism by which an RNA virus can counter the negative effects of elevated mutation rates. IMPORTANCE RNA viruses exist as genetically diverse populations. This standing genetic diversity gives them the potential to adapt rapidly, evolve resistance to antiviral therapeutics, and evade immune responses. Viral mutants with altered mutation rates or mutational tolerance have provided insights into how genetic diversity arises and how it affects the behavior of RNA viruses. To this end, we identified variants within the polymerase complex of influenza virus that are able to tolerate drug-mediated increases in viral mutation rates. We find that drug resistance is highly dependent on interactions among mutations in the polymerase complex. In contrast to other viruses, influenza virus counters the effect of higher mutation rates primarily by maintaining high levels of genome replication. These findings suggest the importance of maintaining large population sizes for viruses with high mutation rates and show that multiple proteins can affect both mutation rate and genome synthesis.

Characterization of proteins with Siaα2-3/6Gal-linked glycans from bovine milk and role of their glycans against influenza A virus

2018 ◽  
Vol 9 (10) ◽  
pp. 5198-5208 ◽  
Author(s):  
Hanjie Yu ◽  
Yaogang Zhong ◽  
Zhiwei Zhang ◽  
Xiawei Liu ◽  
Kun Zhang ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Bovine Milk ◽  
Milk Proteins ◽  
Biological Functions ◽  
Wide Range ◽  
Range Of Functions ◽  
Bovine Milk Proteins

The bovine milk proteins have a wide range of functions, but the role of the attached glycans in their biological functions has not been fully understood yet.

scholarly journals Memory regulatory T cells home to the lung and control influenza A virus infection

2019 ◽  
Vol 97 (9) ◽  
pp. 774-786 ◽  
Author(s):  
Chunni Lu ◽  
Damien Zanker ◽  
Peter Lock ◽  
Xiangrui Jiang ◽  
Jieru Deng ◽  
...  
Keyword(s):  
T Cells ◽  
Virus Infection ◽  
Regulatory T Cells ◽  
Influenza A Virus ◽  
Influenza A ◽  
Influenza A Virus Infection ◽  
And Control

scholarly journals Age at Vaccination and Timing of Infection Do Not Alter Vaccine-Associated Enhanced Respiratory Disease in Influenza A Virus-Infected Pigs

2016 ◽  
Vol 23 (6) ◽  
pp. 470-482 ◽  
Author(s):  
Carine K. Souza ◽  
Daniela S. Rajão ◽  
Crystal L. Loving ◽  
Phillip C. Gauger ◽  
Daniel R. Pérez ◽  
...  
Keyword(s):  
Respiratory Disease ◽  
Influenza A Virus ◽  
Influenza A ◽  
Control Groups ◽  
Swine Industry ◽  
Vaccine Component ◽  
Live Attenuated Influenza Virus ◽  
And Control ◽  
The Impact

ABSTRACTWhole inactivated virus (WIV) vaccines are widely used in the swine industry to reduce clinical disease against homologous influenza A virus (IAV) infection. In pigs experimentally challenged with antigenically distinct heterologous IAV of the same hemagglutinin subtype, WIV vaccinates have been shown to develop vaccine-associated enhanced respiratory disease (VAERD). We evaluated the impact of vaccine valency, age at vaccination, and duration between vaccination and challenge on the development of VAERD using vaccine containing δ1-H1N2 and challenge with pandemic H1N1 (pH1N1) virus. Pigs were vaccinated with monovalent WIV MN08 (δ1-H1N2) and bivalent (δ1-H1N2–H3N2 or δ1-H1N2–pH1N1) vaccines and then were challenged with pH1N1 at 3 weeks postboost (wpb). Another group was vaccinated with the same monovalent WIV and challenged at 6 wpb to determine if the time postvaccination plays a role in the development of VAERD. In a follow-up study, the impact of age of first WIV vaccination (at 4 versus 9 weeks of age) with a boost 3 weeks later (at 7 versus 12 weeks of age) was evaluated. A monovalent live-attenuated influenza virus (LAIV) vaccine administered at 4 and 7 weeks of age was also included. All mismatched WIV groups had significantly higher lung lesions than the LAIV, bivalent MN08-CA09, and control groups. Age of first vaccination or length of time between booster dose and subsequent challenge did not alter the development of VAERD in WIV-vaccinated pigs. Importantly, the mismatched component of the bivalent MN08-CA09 WIV did not override the protective effect of the matched vaccine component.

scholarly journals Differential Contribution of PB1-F2 to the Virulence of Highly Pathogenic H5N1 Influenza A Virus in Mammalian and Avian Species

2011 ◽  
Vol 7 (8) ◽  
pp. e1002186 ◽  
Author(s):  
Mirco Schmolke ◽  
Balaji Manicassamy ◽  
Lindomar Pena ◽  
Troy Sutton ◽  
Rong Hai ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Avian Species ◽  
Highly Pathogenic ◽  
H5n1 Influenza ◽  
Pathogenic H5n1 ◽  
Differential Contribution

scholarly journals Low fidelity assembly of influenza A virus promotes escape from host cells

2018 ◽  
Author(s):  
Michael D. Vahey ◽  
Daniel A. Fletcher
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Phenotypic Variability ◽  
Morphological Variability ◽  
Influenza Viruses ◽  
Host Cells ◽  
Temperature Changes ◽  
Wide Range ◽  
Infected Cells ◽  
Protein Components

AbstractInfluenza viruses inhabit a wide range of host environments using a limited repertoire of protein components. Unlike viruses with stereotyped shapes, influenza produces virions with significant morphological variability even within clonal populations. Whether this tendency to form pleiomorphic virions is coupled to compositional heterogeneity and whether it affects replicative fitness remains unclear. Here we address these questions by developing live strains of influenza A virus amenable to rapid compositional characterization through quantitative, site-specific labeling of viral proteins. Using these strains, we find that influenza A produces virions with broad variations in size and composition from even single infected cells. The virus leverages this phenotypic variability to survive environmental challenges including temperature changes and anti-virals. Complimenting genetic adaptations that act over larger populations and longer times, this ‘low fidelity’ assembly of influenza A virus allows small populations to survive environments that fluctuate over individual replication cycles.

scholarly journals Influenza A virus superinfection potential is regulated by viral genomic heterogeneity

2018 ◽  
Author(s):  
Jiayi Sun ◽  
Christopher B. Brooke
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Control Strategies ◽  
Natural Infection ◽  
Viral Gene ◽  
Evolutionary Potential ◽  
Viral Genes ◽  
Prediction And Control ◽  
Complete Set ◽  
And Control

AbstractDefining the specific factors that govern the evolution and transmission of influenza A virus (IAV) populations is of critical importance for designing more effective prediction and control strategies. Superinfection, the sequential infection of a single cell by two or more virions, plays an important role in determining the replicative and evolutionary potential of IAV populations. The prevalence of superinfection during natural infection, and the specific mechanisms that regulate it, remain poorly understood. Here, we used a novel single virion infection approach to directly assess the effects of individual IAV genes on superinfection efficiency. Rather than implicating a specific viral gene, this approach revealed that superinfection susceptibility is determined by the total number of viral genes expressed, independent of their identity. IAV particles that expressed a complete set of viral genes potently inhibit superinfection, while semi-infectious particles (SIPs) that express incomplete subsets of viral genes do not. As a result, virus populations that contain more SIPs undergo more frequent superinfection. These findings identify both a major determinant of IAV superinfection potential and a prominent role for SIPs in promoting viral co-infection.

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