scholarly journals Triple reassortment increases compatibility among viral ribonucleoprotein genes of contemporary avian and human influenza A viruses

2021 ◽  
Vol 17 (10) ◽  
pp. e1009962
Author(s):  
Kaitlyn Waters ◽  
Cheng Gao ◽  
Matthew Ykema ◽  
Lei Han ◽  
Lynden Voth ◽  
...  
Keyword(s):  
Influenza A ◽  
Rna Binding ◽  
Human Influenza ◽  
Influenza A Viruses ◽  
Binding Motifs ◽  
Replication Efficiency ◽  
Human Interface ◽  
2009 H1n1 ◽  
Multiple Strains ◽  
Viral Replication Efficiency

Compatibility among the influenza A virus (IAV) ribonucleoprotein (RNP) genes affects viral replication efficiency and can limit the emergence of novel reassortants, including those with potential pandemic risks. In this study, we determined the polymerase activities of 2,451 RNP reassortants among three seasonal and eight enzootic IAVs by using a minigenome assay. Results showed that the 2009 H1N1 RNP are more compatible with the tested enzootic RNP than seasonal H3N2 RNP and that triple reassortment increased such compatibility. The RNP reassortants among 2009 H1N1, canine H3N8, and avian H4N6 IAVs had the highest polymerase activities. Residues in the RNA binding motifs and the contact regions among RNP proteins affected polymerase activities. Our data indicates that compatibility among seasonal and enzootic RNPs are selective, and enzoosis of multiple strains in the animal-human interface can facilitate emergence of an RNP with increased replication efficiency in mammals, including humans.

scholarly journals Tissue Tropisms of Avian Influenza A Viruses Affect Their Spillovers from Wild Birds to Pigs

2020 ◽  
Vol 94 (24) ◽  
Author(s):  
Xiaojian Zhang ◽  
Fred L. Cunningham ◽  
Lei Li ◽  
Katie Hanson-Dorr ◽  
Liyuan Liu ◽  
...  
Keyword(s):  
Viral Replication ◽  
Receptor Binding ◽  
Influenza A ◽  
Phenotypic Trait ◽  
Influenza A Viruses ◽  
Replication Efficiency ◽  
Binding Preference ◽  
Upper Respiratory ◽  
Tissue Tropisms ◽  
Viral Replication Efficiency

ABSTRACT Wild aquatic birds maintain a large, genetically diverse pool of influenza A viruses (IAVs), which can be transmitted to lower mammals and, ultimately, humans. Through phenotypic analyses of viral replication efficiency, only a small set of avian IAVs were found to replicate well in epithelial cells of the swine upper respiratory tract, and these viruses were shown to infect and cause virus shedding in pigs. Such a phenotypic trait of the viral replication efficiency appears to emerge randomly and is distributed among IAVs across multiple avian species and geographic and temporal orders. It is not determined by receptor binding preference but is determined by other markers across genomic segments, such as those in the ribonucleoprotein complex. This study demonstrates that phenotypic variants of viral replication efficiency exist among avian IAVs but that only a few of these may result in viral shedding in pigs upon infection, providing opportunities for these viruses to become adapted to pigs, thus posing a higher potential risk for creating novel variants or detrimental reassortants within pig populations. IMPORTANCE Swine serve as a mixing vessel for generating pandemic strains of human influenza virus. All hemagglutinin subtypes of IAVs can infect swine; however, only sporadic cases of infection with avian IAVs are reported in domestic swine. The molecular mechanisms affecting the ability of avian IAVs to infect swine are still not fully understood. From the findings of phenotypic analyses, this study suggests that the tissue tropisms (i.e., in swine upper respiratory tracts) of avian IAVs affect their spillovers from wild birds to pigs. It was found that this phenotype is determined not by receptor binding preference but is determined by other markers across genomic segments, such as those in the ribonucleoprotein complex. In addition, our results show that such a phenotypic trait was sporadically and randomly distributed among IAVs across multiple avian species and geographic and temporal orders. This study suggests an efficient way for assessment of the risk posed by avian IAVs, such as in evaluating their potentials to be transmitted from birds to pigs.

scholarly journals Assessment of exposure to influenza A viruses in pigs between weaning and market age

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Juliana Bonin Ferreira ◽  
Zvonimir Poljak ◽  
Robert Friendship ◽  
Éva Nagy ◽  
Greg Wideman ◽  
...  
Keyword(s):  
Influenza A ◽  
Production Systems ◽  
Influenza A Viruses ◽  
Ha Gene ◽  
Testing Strategies ◽  
Common Causes ◽  
Nasal Swabs ◽  
Antibody Titers ◽  
2009 H1n1 ◽  
Low Prevalence

AbstractInfluenza A viruses (IAVs) are common causes of respiratory infection in pigs. The objective of this study was to characterize the circulation of IAVs between weaning and market age on the basis of development of antibody response and molecular epidemiology of detected viruses. Two batches of weaned pigs were followed in the nursery and finisher barns with a sample of 81 and 75 pigs. Nasal swabs and blood samples were collected from individual pigs for virological and serological analyses. A H3N2 subtype virus, of cluster IV, was detected in Study 1, with a maximum of 97.9% identity to HA gene of viruses previously isolated in Ontario. In Study 2, a H1N1 subtype virus, of 2009 H1N1 pandemic lineage, was detected, with a maximum of 97.8% identity to HA gene of viruses previously isolated in Ontario. On the basis of HA gene, it was observed that pigs were being detected with the same virus over time. The existence of antibody titers for IAV other than the isolated one confirmed that more than one subtype can circulate in the same population. In Study 1, pigs with higher numbers of IAV detection had lower serological titers for the same virus that was confirmed to circulate in the nursery (P < 0.01). Thorough knowledge of all endemic viral strains is fundamental for development of infection and disease control, particularly in complex production systems. This may include consideration of sampling and testing strategies which could detect circulation of all IAV variants, even if they have low prevalence.

scholarly journals Non-random reassortment in human influenza A viruses

2008 ◽  
Vol 2 (1) ◽  
pp. 9-22 ◽  
Author(s):  
Raul Rabadan ◽  
Arnold J. Levine ◽  
Michael Krasnitz
Keyword(s):  
Influenza A ◽  
Human Influenza ◽  
Influenza A Viruses

scholarly journals N-Glycolylneuraminic Acid in Animal Models for Human Influenza A Virus

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 815
Author(s):  
Cindy M. Spruit ◽  
Nikoloz Nemanichvili ◽  
Masatoshi Okamatsu ◽  
Hiromu Takematsu ◽  
Geert-Jan Boons ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Animal Models ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Influenza Viruses ◽  
Upper Respiratory Tract ◽  
Human Influenza ◽  
Influenza A Viruses ◽  
Sialic Acid Content ◽  
Acetylneuraminic Acid

The first step in influenza virus infection is the binding of hemagglutinin to sialic acid-containing glycans present on the cell surface. Over 50 different sialic acid modifications are known, of which N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) are the two main species. Animal models with α2,6 linked Neu5Ac in the upper respiratory tract, similar to humans, are preferred to enable and mimic infection with unadapted human influenza A viruses. Animal models that are currently most often used to study human influenza are mice and ferrets. Additionally, guinea pigs, cotton rats, Syrian hamsters, tree shrews, domestic swine, and non-human primates (macaques and marmosets) are discussed. The presence of NeuGc and the distribution of sialic acid linkages in the most commonly used models is summarized and experimentally determined. We also evaluated the role of Neu5Gc in infection using Neu5Gc binding viruses and cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH)-/- knockout mice, which lack Neu5Gc and concluded that Neu5Gc is unlikely to be a decoy receptor. This article provides a base for choosing an appropriate animal model. Although mice are one of the most favored models, they are hardly naturally susceptible to infection with human influenza viruses, possibly because they express mainly α2,3 linked sialic acids with both Neu5Ac and Neu5Gc modifications. We suggest using ferrets, which resemble humans closely in the sialic acid content, both in the linkages and the lack of Neu5Gc, lung organization, susceptibility, and disease pathogenesis.

scholarly journals Improving pandemic influenza risk assessment

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Colin A Russell ◽  
Peter M Kasson ◽  
Ruben O Donis ◽  
Steven Riley ◽  
John Dunbar ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Pandemic Influenza ◽  
Influenza A ◽  
Sequence Data ◽  
Virus Genome ◽  
Influenza Viruses ◽  
Influenza Surveillance ◽  
Human Influenza ◽  
Influenza A Viruses ◽  
Virus Genotype

Assessing the pandemic risk posed by specific non-human influenza A viruses is an important goal in public health research. As influenza virus genome sequencing becomes cheaper, faster, and more readily available, the ability to predict pandemic potential from sequence data could transform pandemic influenza risk assessment capabilities. However, the complexities of the relationships between virus genotype and phenotype make such predictions extremely difficult. The integration of experimental work, computational tool development, and analysis of evolutionary pathways, together with refinements to influenza surveillance, has the potential to transform our ability to assess the risks posed to humans by non-human influenza viruses and lead to improved pandemic preparedness and response.

scholarly journals Large-Scale Sequence Analysis of M Gene of Influenza A Viruses from Different Species: Mechanisms for Emergence and Spread of Amantadine Resistance

2009 ◽  
Vol 53 (10) ◽  
pp. 4457-4463 ◽  
Author(s):  
Yuki Furuse ◽  
Akira Suzuki ◽  
Hitoshi Oshitani
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Drug Resistant ◽  
Human Influenza ◽  
Influenza A Viruses ◽  
M Gene ◽  
Drug Pressure ◽  
Human Influenza Virus ◽  
Selective Pressures ◽  
Amantadine Resistance

ABSTRACT Influenza A virus infects many species, and amantadine is used as an antiviral agent. Recently, a substantial increase in amantadine-resistant strains has been reported, most of which have a substitution at amino acid position 31 in the M2 gene. Understanding the mechanism responsible for the emergence and spread of antiviral resistance is important for developing a treatment protocol for seasonal influenza and for deciding on a policy for antiviral stockpiling for pandemic influenza. The present study was conducted to identify the existence of drug pressure on the emergence and spread of amantadine-resistant influenza A viruses. We analyzed data on more than 5,000 virus sequences and constructed a phylogenetic tree to calculate selective pressures on sites in the M2 gene associated with amantadine resistance (positions 26, 27, 30, and 31) among different hosts. The phylogenetic tree revealed that the emergence and spread of the drug-resistant M gene in different hosts and subtypes were independent and not through reassortment. For human influenza virus, positive selection was detected only at position 27. Selective pressures on the sites were not always higher for human influenza virus than for viruses of other hosts. Additionally, selective pressure on position 31 did not increase after the introduction of amantadine. Although there is a possibility of drug pressure on human influenza virus, we could not find positive pressure on position 31. Because the recent rapid increase in drug-resistant virus is associated with the substitution at position 31, the resistance may not be related to drug use.

scholarly journals Virus persistence in pig herds led to successive reassortment events between swine and human influenza A viruses, resulting in the emergence of a novel triple-reassortant swine influenza virus

2019 ◽  
Vol 50 (1) ◽  
Author(s):  
Amélie Chastagner ◽  
Emilie Bonin ◽  
Christelle Fablet ◽  
Stéphane Quéguiner ◽  
Edouard Hirchaud ◽  
...  
Keyword(s):  
Influenza A ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
Infection Risk ◽  
Pandemic H1n1 ◽  
Human Influenza ◽  
Influenza A Viruses ◽  
Virus Persistence ◽  
Zoonotic Viruses ◽  
Swine Influenza A Virus

Abstract This report describes the detection of a triple reassortant swine influenza A virus of H1avN2 subtype. It evolved from an avian-like swine H1avN1 that first acquired the N2 segment from a seasonal H3N2, then the M segment from a 2009 pandemic H1N1, in two reassortments estimated to have occurred 10 years apart. This study illustrates how recurrent influenza infections increase the co-infection risk and facilitate evolutionary jumps by successive gene exchanges. It recalls the importance of appropriate biosecurity measures inside holdings to limit virus persistence and interspecies transmissions, which both contribute to the emergence of new potentially zoonotic viruses.

scholarly journals Cooperation between the Hemagglutinin of Avian Viruses and the Matrix Protein of Human Influenza A Viruses

2002 ◽  
Vol 76 (4) ◽  
pp. 1781-1786 ◽  
Author(s):  
Christoph Scholtissek ◽  
Jürgen Stech ◽  
Scott Krauss ◽  
Robert G. Webster
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Matrix Protein ◽  
Gene Products ◽  
Human Influenza ◽  
Influenza A Viruses ◽  
M Gene ◽  
Human Virus ◽  
Ha Gene ◽  
M Proteins

ABSTRACT To analyze the compatibility of avian influenza A virus hemagglutinins (HAs) and human influenza A virus matrix (M) proteins M1 and M2, we doubly infected Madin-Darby canine kidney cells with amantadine (1-aminoadamantane hydrochloride)-resistant human viruses and amantadine-sensitive avian strains. By using antisera against the human virus HAs and amantadine, we selected reassortants containing the human virus M gene and the avian virus HA gene. In our system, high virus yields and large, well-defined plaques indicated that the avian HAs and the human M gene products could cooperate effectively; low virus yields and small, turbid plaques indicated that cooperation was poor. The M gene products are among the primary components that determine the species specificities of influenza A viruses. Therefore, our system also indicated whether the avian HA genes effectively reassorted into the genome and replaced the HA gene of the prevailing human influenza A viruses. Most of the avian HAs that we tested efficiently cooperated with the M gene products of the early human A/PR/8/34 (H1N1) virus; however, the avian HAs did not effectively cooperate with the most recently isolated human virus that we tested, A/Nanchang/933/95 (H3N2). Cooperation between the avian HAs and the M proteins of the human A/Singapore/57 (H2N2) virus was moderate. These results suggest that the currently prevailing human influenza A viruses might have lost their ability to undergo antigenic shift and therefore are unable to form new pandemic viruses that contain an avian HA, a finding that is of great interest for pandemic planning.

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