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Antigenic drift of H1N1 influenza A virus in pigs with and without passive immunity.

ABSTRACT: BACKGROUND:The genetic and antigenic characteristics of influenza A viruses (IAV) within and between species change over time due to antigenic shift and drift. Although pigs are known to play a key role in the epidemiology of IAV between species, little is known about the molecular evolution of IAV hemagglutinin (HA) in pigs. OBJECTIVES:The aim of this study was to evaluate the HA drift of an H1N1 IAV after infecting weaned pigs with or without maternally derived passive immunity. METHODS:Three- to four-week-old piglets born either to vaccinated or unvaccinated sows were contact-infected upon exposure with an IAV-infected pig. Nasal swabs were collected daily from each pig and tested for IAV by RRT-PCR. Full-length HA sequences were obtained directly from positive nasal swabs and compared between groups. RESULTS:Synonymous and non-synonymous mutations were detected in pigs with and without passive immunity. Most of the non-synonymous mutations occurred within the HA1 region of the HA. Changes within HA1 region were only identified in antigenic site B in pigs without passive immunity and in antigenic sites A, B, and D in pigs with passive immunity. However, there was no association between the immune status of the pig and the amino acid substitutions observed. CONCLUSIONS:Overall, we demonstrated that amino acid substitutions within antigenic sites can happen in weaned pigs with or without passive immunity shortly after infection.

SUBMITTER: Diaz A

PROVIDER: S-EPMC4942991 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Antigenic drift of H1N1 influenza A virus in pigs with and without passive immunity.

Diaz Andres A Allerson Matthew M Culhane Marie M Sreevatsan Srinand S Torremorell Montserrat M

Influenza and other respiratory viruses 20131201

<h4>Background</h4>The genetic and antigenic characteristics of influenza A viruses (IAV) within and between species change over time due to antigenic shift and drift. Although pigs are known to play a key role in the epidemiology of IAV between species, little is known about the molecular evolution of IAV hemagglutinin (HA) in pigs.<h4>Objectives</h4>The aim of this study was to evaluate the HA drift of an H1N1 IAV after infecting weaned pigs with or without maternally derived passive immunity. ...[more]

PMID: 24224820

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Project description:Surveillance data indicate that most circulating A(H1N1)pdm09 influenza viruses have remained antigenically similar since they emerged in humans in 2009. However, antigenic drift is likely to occur in the future in response to increasing population immunity induced by infection or vaccination. In this study, sequential passaging of A(H1N1)pdm09 virus by contact transmission through two independent series of suboptimally vaccinated ferrets resulted in selection of variant viruses with an amino acid substitution (N156K, H1 numbering without signal peptide; N159K, H3 numbering without signal peptide; N173K, H1 numbering from first methionine) in a known antigenic site of the viral HA. The N156K HA variant replicated and transmitted efficiently between naïve ferrets and outgrew wildtype virus in vivo in ferrets in the presence and absence of immune pressure. In vitro, in a range of cell culture systems, the N156K variant rapidly adapted, acquiring additional mutations in the viral HA that also potentially affected antigenic properties. The N156K escape mutant was antigenically distinct from wildtype virus as shown by binding of HA-specific antibodies. Glycan binding assays demonstrated the N156K escape mutant had altered receptor binding preferences compared to wildtype virus, which was supported by computational modeling predictions. The N156K substitution, and culture adaptations, have been detected in human A(H1N1)pdm09 viruses with N156K preferentially reported in sequences from original clinical samples rather than cultured isolates. This study demonstrates the ability of the A(H1N1)pdm09 virus to undergo rapid antigenic change to evade a low level vaccine response, while remaining fit in a ferret transmission model of immunization and infection. Furthermore, the potential changes in receptor binding properties that accompany antigenic changes highlight the importance of routine characterization of clinical samples in human A(H1N1)pdm09 influenza surveillance.

Dataset Information

Antigenic drift of H1N1 influenza A virus in pigs with and without passive immunity.

Publications

Antigenic drift of H1N1 influenza A virus in pigs with and without passive immunity.

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