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.

scholarly journals Influenza A Virus Superinfection Potential Is Regulated by Viral Genomic Heterogeneity

mBio ◽  
2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Jiayi Sun ◽  
Christopher B. Brooke
Keyword(s):  
Single Cell ◽  
Influenza A Virus ◽  
Influenza A ◽  
Natural Infection ◽  
Viral Gene ◽  
Evolutionary Potential ◽  
Viral Genes ◽  
A Cell ◽  
Complete Set ◽  
Sequential Infection

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 gene segments expressed within a cell. IAV particles that express 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. We further demonstrate that viral replicase activity is responsible for inhibiting subsequent infection. These findings identify both a major determinant of IAV superinfection potential and a prominent role for SIPs in promoting viral coinfection.IMPORTANCESuperinfection, the sequential infection of a single cell by two or more virions, plays an important role in determining the replicative and evolutionary potential of influenza A virus (IAV) populations. The specific mechanisms that regulate superinfection during natural infection remain poorly understood. Here, we show that superinfection susceptibility is determined by the total number of viral genes expressed within a cell and is independent of their specific identity. Virions that express a complete set of viral genes potently inhibit superinfection, while the semi-infectious particles (SIPs) that make up the bulk of IAV populations and express incomplete subsets of viral genes do not. As a result, viral populations with more SIPs undergo more-frequent superinfection. These findings identify both the primary determinant of IAV superinfection potential and a prominent role for SIPs in promoting coinfection.

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 The Polymerase Acidic Protein Gene of Influenza A Virus Contributes to Pathogenicity in a Mouse Model

2009 ◽  
Vol 83 (23) ◽  
pp. 12325-12335 ◽  
Author(s):  
Min-Suk Song ◽  
Philippe Noriel Q. Pascua ◽  
Jun Han Lee ◽  
Yun Hee Baek ◽  
Ok-Jun Lee ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Mammalian Cells ◽  
Influenza A ◽  
Lethal Dose ◽  
Influenza Viruses ◽  
Mammalian Host ◽  
Viral Gene ◽  
Avian Influenza Viruses ◽  
Range Restriction ◽  
Viral Genes

ABSTRACT Adaptation of influenza A viruses to a new host species usually involves the mutation of one or more of the eight viral gene segments, and the molecular basis for host range restriction is still poorly understood. To investigate the molecular changes that occur during adaptation of a low-pathogenic avian influenza virus subtype commonly isolated from migratory birds to a mammalian host, we serially passaged the avirulent wild-bird H5N2 strain A/Aquatic bird/Korea/W81/05 (W81) in the lungs of mice. The resulting mouse-adapted strain (ma81) was highly virulent (50% mouse lethal dose = 2.6 log10 50% tissue culture infective dose) and highly lethal. Nonconserved mutations were observed in six viral genes (those for PB2, PB1, PA, HA, NA, and M). Reverse genetic experiments substituting viral genes and mutations demonstrated that the PA gene was a determinant of the enhanced virulence in mice and that a Thr-to-Iso substitution at position 97 of PA played a key role. In growth kinetics studies, ma81 showed enhanced replication in mammalian but not avian cell lines; the PA97I mutation in strain W81 increased its replicative fitness in mice but not in chickens. The high virulence associated with the PA97I mutation in mice corresponded to considerably enhanced polymerase activity in mammalian cells. Furthermore, this characteristic mutation is not conserved among avian influenza viruses but is prevalent among mouse-adapted strains, indicating a host-dependent mutation. To our knowledge, this is the first study that the isoleucine residue at position 97 in PA plays a key role in enhanced virulence in mice and is implicated in the adaptation of avian influenza viruses to mammalian hosts.

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 Dysregulation of M segment gene expression contributes to influenza A virus host restriction

2019 ◽  
Author(s):  
Brenda M. Calderon ◽  
Shamika Danzy ◽  
Gabrielle K. Delima ◽  
Nathan T. Jacobs ◽  
Ketaki Ganti ◽  
...  
Keyword(s):  
Gene Expression ◽  
Influenza A Virus ◽  
Mammalian Cells ◽  
Influenza A ◽  
Viral Gene Expression ◽  
Host Adaptation ◽  
Model Systems ◽  
Viral Gene ◽  
M2 Protein ◽  
Viral Growth

AbstractThe M segment of the 2009 pandemic influenza A virus (IAV) has been implicated in its emergence into human populations. To elucidate the genetic contributions of the M segment to host adaptation, and the underlying mechanisms, we examined a panel of isogenic viruses that carry avian- or human-derived M segments. Avian, but not human, M segments restricted viral growth and transmission in mammalian model systems, and the restricted growth correlated with increased expression of M2 relative to M1. M2 overexpression was associated with intracellular accumulation of autophagosomes, which was alleviated by interference of the viral proton channel activity by amantadine treatment. As M1 and M2 are expressed from the M mRNA through alternative splicing, we separated synonymous and non-synonymous changes that differentiate human and avian M segments and found that dysregulation of gene expression leading to M2 overexpression diminished replication, irrespective of amino acid composition of M1 or M2. Moreover, in spite of efficient replication, virus possessing a human M segment that expressed avian M2 protein at low level did not transmit efficiently. We conclude that (i) determinants of transmission reside in the IAV M2 protein, and that (ii) control of M segment gene expression is a critical aspect of IAV host adaptation needed to prevent M2-mediated dysregulation of vesicular homeostasis.Author summaryInfluenza A virus (IAV) pandemics arise when a virus adapted to a non-human host overcomes species barriers to successfully infect humans and sustain human-to-human transmission. To gauge the adaptive potential and therefore pandemic risk posed by a particular IAV, it is critical to understand the mechanisms underlying viral adaptation to human hosts. Here, we focused on the role of one of IAV’s eight gene segments, the M segment, in host adaptation. Comparing the growth of IAVs with avian- and human-derived M segments in avian and mammalian systems revealed that the avian M segment restricts viral growth specifically in mammalian cells. We show that the mechanism underlying this host range phenotype is a dysregulation of viral gene expression when the avian IAV M segment is transcribed in mammalian cells. In particular, excess production of the M2 protein results in viral interference with cellular functions on which the virus relies. Our results therefore reveal that the use of cellular machinery to control viral gene expression leaves the virus vulnerable to over- or under-production of critical viral gene products in a new host species.

scholarly journals Epidemiological Surveillance of Influenza Virus Matrix Gene in Pigs, in Lagos, Nigeria, 2015-2016

2017 ◽  
Vol 2 (1) ◽  
pp. 1-7
Author(s):  
Abdul-Azeez A. Anjorin ◽  
Olumuyiwa B. Salu ◽  
Akeeb O.B. Oyefolu ◽  
Bamidele O. Oke ◽  
James B. Ayorinde ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Pandemic Influenza ◽  
Influenza A ◽  
Virus Disease ◽  
Influenza Viruses ◽  
Epidemiological Surveillance ◽  
Viral Gene ◽  
Cross Sectional ◽  
Matrix Gene

AbstractThe co-infection of different influenza A virus enable viral gene re-assortments especially in pigs that serve as mixing vessel with the possibility of emergence of novel subtypes. Such re-assortants pose serious public health threat, as epitomised by the emergence of pandemic influenza in 2009. In Nigeria, there is mixture of animal species and highly populated densities that can increase the risk of influenza virus endemicity, genetic reshuffling and emergence of future pandemic influenza viruses. Thus, this study was aimed at determining influenza virus disease burden in pigs. This study was a cross sectional molecular surveillance of influenza virus. A total of 194 pig nasal samples from reported cases and randomly sampled were collected from pig farms in Ojo and Ikorodu in Lagos State between October, 2015 and April, 2016. The samples were investigated for the presence of influenza virus matrix gene by Reverse Transcriptase Polymerase Chain Reaction and detected by gel electrophoresis. P-values were calculated using Chi-square and Fisher’s exact tests. The result showed that 25 (12.9%) samples were positive for influenza A virus, out of which, 20 (80%) were samples from Ojo while 5 (20%) were samples from Ikorodu. Epidemiological parameters for the sampled locations, methods either as reported case or randomised, and sex compared were significant at 95% confidence interval. This study determined influenza viral burden in pigs with a molecular prevalence of 12.9% to influenza A. It further confirmed the sub-clinical and clinical circulation of Influenza A virus in pigs in Ojo and Ikorodu in Lagos. Therefore, the detection of influenza A virus in commercial pigs in Nigeria accentuates the importance of continuous surveillance and monitoring of the virus in order to prevent the advent of virulent strains that may spread to Pig-handlers and the community at large.

scholarly journals Influenza A Virus Neuraminidase Enhances Meningococcal Adhesion to Epithelial Cells through Interaction with Sialic Acid-Containing Meningococcal Capsules

2009 ◽  
Vol 77 (9) ◽  
pp. 3588-3595 ◽  
Author(s):  
Marie-Anne Rameix-Welti ◽  
Maria Leticia Zarantonelli ◽  
Dario Giorgini ◽  
Corinne Ruckly ◽  
Monica Marasescu ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Sialic Acid ◽  
Epithelial Cells ◽  
Influenza A Virus ◽  
Influenza A ◽  
Bacterial Infections ◽  
Control Strategies ◽  
Direct Interaction ◽  
Virus Infections ◽  
Meningococcal Infections

ABSTRACT The underlying mechanisms of the epidemiological association between influenza virus infections and Neisseria meningitidis invasive infections are not fully understood. Here we report that adhesion of N. meningitidis to human Hec-1-B epithelial cells is enhanced by influenza A virus (IAV) infection. A potential role of the viral neuraminidase (NA) in facilitating meningococcal adhesion to influenza virus-infected epithelial cells was examined. Expression of a recombinant IAV NA in Hec-1-B human epithelial cells increased the adhesion of strains of N. meningitidis belonging to the sialic acid-containing capsular serogroups B, C, and W135 but not to the mannosamine phosphate-containing capsular serogroup A. Adhesion enhancement was not observed with an inactive NA mutant or in the presence of an NA inhibitor (zanamivir). Furthermore, purified IAV NA was shown to cleave sialic acid-containing capsular polysaccharides of N. meningitidis. On the whole, our findings suggest that a direct interaction between the NA of IAV and the capsule of N. meningitidis enhances bacterial adhesion to cultured epithelial cells, most likely through cleavage of capsular sialic acid-containing polysaccharides. A better understanding of the association between IAV and invasive meningococcal infections should help to set up improved control strategies against these seasonal dual viral-bacterial infections.

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