scholarly journals PERSISTENT ANTIGENIC VARIATION OF INFLUENZA A VIRUSES AFTER INCOMPLETE NEUTRALIZATION IN OVO WITH HETEROLOGOUS IMMUNE SERUM

1950 ◽  
Vol 92 (5) ◽  
pp. 441-462 ◽  
Author(s):  
Italo Archetti ◽  
Frank L. Horsfall

Antigenic variants of influenza A virus strains emerge on serial passage in ovo in the presence of immune serum against different but related strains. An old laboratory strain (PR8) which had been through hundreds of animal passages was as readily modified by this procedure as recently recovered strains. Such variants apparently can be obtained at will and show antigenic patterns which are reproducible and appear to be predictable in terms of the immune serum used for their selection. Variant strains retain their new antigenic patterns on serial passage in ovo in the absence of immune serum. Limited serial passage in ovo of strains in the absence of immune serum did not result in the emergence of antigenic variants. Similarly, serial passages of strains in ovo in the presence of immune serum against widely different strains, which failed to show significant cross-neutralization, did not lead to the appearance of antigenic variants.

Nature ◽  
2012 ◽  
Vol 489 (7417) ◽  
pp. 526-532 ◽  
Author(s):  
Damian C. Ekiert ◽  
Arun K. Kashyap ◽  
John Steel ◽  
Adam Rubrum ◽  
Gira Bhabha ◽  
...  

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Krzysztof Lepek ◽  
Beata Pajak ◽  
Lukasz Rabalski ◽  
Kinga Urbaniak ◽  
Krzysztof Kucharczyk ◽  
...  

Monitoring and control of infections are key parts of surveillance systems and epidemiological risk prevention. In the case of influenza A viruses (IAVs), which show high variability, a wide range of hosts, and a potential of reassortment between different strains, it is essential to study not only people, but also animals living in the immediate surroundings. If understated, the animals might become a source of newly formed infectious strains with a pandemic potential. Special attention should be focused on pigs, because of the receptors specific for virus strains originating from different species, localized in their respiratory tract. Pigs are prone to mixed infections and may constitute a reservoir of potentially dangerous IAV strains resulting from genetic reassortment. It has been reported that a quadruple reassortant, A(H1N1)pdm09, can be easily transmitted from humans to pigs and serve as a donor of genetic segments for new strains capable of infecting humans. Therefore, it is highly desirable to develop a simple, cost-effective, and rapid method for evaluation of IAV genetic variability. We describe a method based on multitemperature single-strand conformational polymorphism (MSSCP), using a fragment of the hemagglutinin (HA) gene, for detection of coinfections and differentiation of genetic variants of the virus, difficult to identify by conventional diagnostic.


1956 ◽  
Vol 103 (4) ◽  
pp. 413-424 ◽  
Author(s):  
Paul Gerber ◽  
Dorothy Hamre ◽  
Clayton G. Loosli

Four successive generations of antigenic variants of influenza PR8-S virus, each derived from the previous one by serial passage in the lungs of mice immunized with the homologous agent, were compared with the original parent PR8-S virus with respect to their serological and immunological character. It was demonstrated by means of H.I., complement-fixation and in ovo-neutralization tests that the variants exhibited a progressively decreasing reactivity with the parent PR8-S antiserum while retaining the ability to elicit antibody to PR8-S influenza virus and to their respective predecessors. Accompanying these changes was a progressive reduction in antigenicity without any significant changes in pathogenicity for mice. Experimental evidence was presented which indicates that the serological changes observed with the variants are not related to the P-Q phenomenon. Antibody absorption tests showed that the variants share antigens with PR8-S virus but differ from it by the presence of specific antigenic components; these increase in quantity with each successive variant while the amount of related antigens shows a progressive decrease. The importance of evaluating the significance of antigenic changes of influenza viruses with active immunity tests was emphasized by the fact that PR8-S vaccine protected mice against fatal infection with lethal doses of the variant strains although the latter had a progressively decreasing serological reactivity with PR8-S antiserum. The inheritable character of the new antigenic properties of the variant strains was demonstrated by their persistence in the absence of thea selective environment following 18 to 24 serial intranasal passages with large inocula in normal mice and following limiting dilution passage in fertile eggs.


2006 ◽  
Vol 17 (1) ◽  
pp. 11-14 ◽  
Author(s):  
JM Conly ◽  
BL Johnston

Influenza A and B viruses are the two major types of influenza viruses that cause human epidemic disease. Influenza A viruses are further categorized into subtypes based on two surface antigens: hemagglutinin (H) and neuraminidase (N). Influenza B viruses are not categorized into subtypes (1). Influenza A viruses are found in many animal species, including humans, ducks, chickens, pigs, whales, horses and seals, whereas influenza B viruses circulate only among humans. The H antigen contains common and strain-specific antigens, demonstrates antigenic variation, and acts as a site of attachment of the virus to host cells to initiate infection (1). The N antigen contains subtype-specific antigens and also demonstrates antigenic variation between subtypes. It is a surface glycoprotein possessing enzymatic activity essential for viral replication in both influenza A and B viruses. The N antigen allows the release of newly produced virions from infected host cells, prevents the formation of viral aggregates after release from the host cells, and prevents viral inactivation by respiratory mucous (2,3). It is thought that this enzyme may also promote viral penetration into respiratory epithelial cells and may contribute to the pathogenicity of the virus by promoting production of proinflammatory cytokines such as interleukin-1 and tumour necrosis factor from macrophages (4-6).


2017 ◽  
Author(s):  
Bernadeta Dadonaite ◽  
Egle Barilaite ◽  
Ervin Fodor ◽  
Alain Laederach ◽  
David L. V. Bauer

Influenza A viruses (IAVs) are segmented single-stranded negative sense RNA viruses that constitute a major threat to human health. The IAV genome consists of eight RNA segments contained in separate viral ribonucleoprotein complexes (vRNPs) that are packaged together into a single virus particle1,2. While IAVs are generally considered to have an unstructured single-stranded genome, it has also been suggested that secondary RNA structures are required for selective packaging of the eight vRNPs into each virus particle3,4. Here, we employ high-throughput sequencing approaches to map both the intra and intersegment RNA interactions inside influenza virions. Our data demonstrate that a redundant network of RNA-RNA interactions is required for vRNP packaging and virus growth. Furthermore, the data demonstrate that IAVs have a much more structured genome than previously thought and the redundancy of RNA interactions between the different vRNPs explains how IAVs maintain the potential for reassortment between different strains, while also retaining packaging selectivity. Our study establishes a framework towards further work into IAV RNA structure and vRNP packaging, which will lead to better models for predicting the emergence of new pandemic influenza strains and will facilitate the development of antivirals specifically targeting genome assembly.


2015 ◽  
Vol 8 (2) ◽  
Author(s):  
Katherine Lien

Through the review of Scholtissek et al.(1), evolution between different strains of influenza A viruses were examined to enable better preparation for future pandemics. Pandemics are the result of antigenic shifts, cumulative reassortants between circulating viruses that form novel gene sequences. The process may produce a virus which a large segment of the population has no immunological memory of, and consequently, are susceptible to the strain.The pandemics in 1918, 1967, 1968 and 2009 were caused by influenza A viruses with hemagglutinin (HA) proteins of 1, 2, or 3 - three out of sixteen known HA subtypes. This raises the question whether pandemics can contain other HA subtypes. Since influenza viruses have segmented genomes, it may require at least two different strains to swap their gene segments in order to co-infect a cell; the better viral compatibility between the parent viruses, the more virulent the reassortant is. A collection of HA subtypes in avian strains and Matrix (M) protein in human strains were used in the experimental model by Scholtissek et al. to examine the recombinants’ survivability and virulence. Although the results conclude that it is not possible for future pandemics to contain other HA subtypes, the work of Scholtissek et al. leads to further research on influenza A reservoirs. Ce document est un résumé au sujet de l'article de Christoph Scholtissek (1) publié en 2002. J’examinerai son modèle expérimental, en mettant en évidence les résultats et donnant un aperçu des recherches plus élaborées. En étudiant des modèles de la coopération entre les virus, ceci permet d’aider à se préparer face aux futures pandémies et épidémies. De tels évènements sont causés par des changements antigéniques produits par l’accumulation de réassortiments entre les virus en circulation et divers éléments. Les virus grippaux A sont en constante évolution, et nécessitent une surveillance constante en anticipation à une pandémie. Les pandémies antérieures, soient celles en 1918, 1957, 1968 et 2009, ont démontré à avoir les hémagglutinines (HA) 1, 2 et 3 – trois des seize sous-types HA possibles. Ceci remet en question la possibilité que les pandémies puissent contenir d’autres sous-types HA. Afin que les virus puissent former des virus réassortis potentiellement nouveaux ils doivent bien coopérer, ce qui est précisément ce que Scholtissek tente d'enquêter. Son modèle expérimental implique des réassortiments entre les différents sous-types d’HA dans des souches aviaires et des souches humaines détenant des M-protéines, afin de déterminer la compatibilité virale. Bien que les résultats concluent qu'il est très peu probable que de futures pandémies détiennent d'autres sous-types HA, ils fournissent des indices du potentiel pandémique. En outre, son article incite la recherche plus à fond sur d’autres réservoirs de la grippe A, les méthodes pour surmonter les barrières entre espèces et le réassortiment efficaces.


1955 ◽  
Vol 101 (6) ◽  
pp. 627-638 ◽  
Author(s):  
Paul Gerber ◽  
Clayton G. Loosli ◽  
Dorothy Hamre

Antigenically different strains of mouse-adapted PR8 influenza A virus have been produced by 17 serial passages of the virus in the lungs of mice immunized with the homologous agent. Comparative serological tests show that the variant strains share antigenic components with the parent strain but the dominant antigen is different. By means of antibody absorption it was shown that the "new" antigenic component of the variant was already present in minor amounts up to the eighth passage and thereafter gained prominence with continued passage in vaccinated mice. Groups of mice vaccinated with either the PR8-S or T21 virus and having comparable antibody titers showed no growth of virus in the lungs following aid-borne challenge with homologous strains. On the other hand, following heterologous air-borne challenge no deaths occurred, but virus grew in the lungs of both groups of vaccinated mice. Almost unrestricted virus multiplication took place in the lungs of mice vaccinated with the parent strain and challenged with the PR8-T21 virus which resulted in extensive consolidation. Less virus grew in the lungs of the mice vaccinated with the variant strains and challenged with the PR8-S virus. In these animals only microscopic evidence of changes due to virus growth in the lungs was observed. The successful serial passage of PR8 influenza A virus in immunized animals was dependent on the initial selection of mice with uniformly low H.I. antibody titers as determined on tail blood, and the intranasal instillation of sufficient virus to favor the survival of those virus particles least related to the antibodies present. The epidemiological implications of these observations are discussed briefly.


2021 ◽  
Vol 102 (3) ◽  
Author(s):  
Anabel L. Clements ◽  
Thomas P. Peacock ◽  
Joshua E. Sealy ◽  
Hui Min Lee ◽  
Saira Hussain ◽  
...  

Influenza A viruses encode several accessory proteins that have host- and strain-specific effects on virulence and replication. The accessory protein PA-X is expressed due to a ribosomal frameshift during translation of the PA gene. Depending on the particular combination of virus strain and host species, PA-X has been described as either acting to reduce or increase virulence and/or virus replication. In this study, we set out to investigate the role PA-X plays in H9N2 avian influenza viruses, focusing on the natural avian host, chickens. We found that the G1 lineage A/chicken/Pakistan/UDL-01/2008 (H9N2) PA-X induced robust host shutoff in both mammalian and avian cells and increased virus replication in mammalian, but not avian cells. We further showed that PA-X affected embryonic lethality in ovo and led to more rapid viral shedding and widespread organ dissemination in vivo in chickens. Overall, we conclude PA-X may act as a virulence factor for H9N2 viruses in chickens, allowing faster replication and wider organ tropism.


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