Genotype patterns of contemporary reassorted H3N2 virus in US swine

To understand the evolution of swine-origin H3N2v influenza viruses that have infected 320 humans in the USA since August 2011, we performed a phylogenetic analysis at a whole genome scale of North American swine influenza viruses (n = 200). All viral isolates evolved from the prototypical North American H3 cluster 4 (c4), with evidence for further diversification into subclusters. At least ten distinct reassorted H3N2/pandemic H1N1 (rH3N2p) genotypes were identified in swine. Genotype 1 (G1) was most frequently detected in swine and all human H3N2v viruses clustered within a single G1 clade. These data suggest that the genetic requirements for transmission to humans may be restricted to a specific subset of swine viruses. Mutations at putative antigenic sites as well as reduced serological cross-reactivity among the H3 subclusters suggest antigenic drift of these contemporary viruses.

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Lower seroreactivity to European than to North American H3N2 swine influenza viruses in humans, Luxembourg, 2010

Eurosurveillance ◽

10.2807/1560-7917.es2015.20.13.21078 ◽

2015 ◽

Vol 20 (13) ◽

Cited By ~ 4

Author(s):

Y Qiu ◽

C P Muller ◽

K Van Reeth

Keyword(s):

Human Serum ◽

North American ◽

Strong Correlation ◽

Haemagglutination Inhibition ◽

Swine Influenza ◽

Cross Reactivity ◽

Influenza Viruses ◽

Serum Samples ◽

Human Serum Samples ◽

The North

Seroreactivity to H3N2 swine influenza viruses (SIVs) was evaluated in serum samples collected from 843 people aged 0 to 100 years in 2010 in Luxembourg. Sera were analysed by haemagglutination inhibition (HI) and virus neutralisation (VN) assays targeting a European H3N2 SIV, a North American H3N2 variant of swine origin (H3N2v) and human seasonal H3N2 viruses isolated in 1975, 1995 and 2005. HI antibodies (titre?≥?10) against European H3N2 SIV were almost exclusively detected in those born before 1990, of whom 70% were seropositive. HI antibodies against H3N2v were predominantly found in those born before 2000, with 86% seropositive. Titres against the North American H3N2v were higher than against the European H3N2 SIV. VN patterns were similar, but with higher rates and titres. We also demonstrated lower seroreactivity to European H3N2 SIV than to North American H3N2v virus. Finally, we found a strong correlation between HI titres against the European H3N2 SIV and H3N2v and their respective human ancestors, A/Victoria/3/75 and A/Nanchang/933/95. This finding and the minimal contacts between humans and pigs in Luxembourg suggest that anti-SIV antibodies in human serum samples reflect serological cross-reactivity with historical human H3N2 viruses. Our findings help assess the pandemic risk of H3N2 SIV.

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Antigenic and genetic diversity among swine influenza A H1N1 and H1N2 viruses in Europe

Journal of General Virology ◽

10.1099/0022-1317-83-4-735 ◽

2002 ◽

Vol 83 (4) ◽

pp. 735-745 ◽

Cited By ~ 83

Author(s):

S. Marozin ◽

V. Gregory ◽

K. Cameron ◽

M. Bennett ◽

M. Valette ◽

...

Keyword(s):

Genetic Diversity ◽

Influenza A ◽

Swine Influenza ◽

Influenza Viruses ◽

Antigenic Drift ◽

H3n2 Virus ◽

Human Populations ◽

Antigenic Variant ◽

Influenza A H1n1 ◽

The Uk

Three subtypes of influenza A viruses, H1N1, H1N2 and H3N2, co-evolve in pigs in Europe. H1N2 viruses isolated from pigs in France and Italy since 1997 were closely related to the H1N2 viruses which emerged in the UK in 1994. In particular, the close relationship of the neuraminidases (NAs) of these viruses to the NA of a previous UK H3N2 swine virus indicated that they had not acquired the NA from H3N2 swine viruses circulating in continental Europe. Moreover, antigenic and genetic heterogeneity among the H1N2 viruses appeared to be due in part to multiple introductions of viruses from the UK. On the other hand, comparisons of internal gene sequences indicated genetic exchange between the H1N2 viruses and co-circulating H1N1 and/or H3N2 subtypes. Most genes of the earlier (1997–1998) H1N2 isolates were more closely related to those of a contemporary French H1N1 isolate, whereas the genes of later (1999–2000) isolates, including the HAs of some H1N2 viruses, were closely related to those of a distinct H1N1 antigenic variant which emerged in France in 1999. In contrast, an H3N2 virus isolated in France in 1999 was closely related antigenically and genetically to contemporary human A/Sydney/5/97-like viruses. These studies reveal interesting parallels between genetic and antigenic drift of H1N1 viruses in pig and human populations, and provide further examples of the contribution of genetic reassortment to the antigenic and genetic diversity of swine influenza viruses and the importance of the complement of internal genes in the evolution of epizootic strains.

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A Single Amino Acid at Position 158 in Hemagglutinin Affects the Antigenic Property of Eurasian Avian-like H1N1 Swine Influenza Viruses

10.22541/au.162201750.02228441/v1 ◽

2021 ◽

Author(s):

Zeng Wang ◽

Yan Chen ◽

Huayuan Chen ◽

Fei Meng ◽

Shiyu Tao ◽

...

Keyword(s):

Influenza Virus ◽

Amino Acid ◽

Antigenic Variation ◽

Swine Influenza ◽

Antigenic Property ◽

Cross Reactivity ◽

Influenza Viruses ◽

Antigenic Drift ◽

Single Amino Acid ◽

Ha Protein

Influenza viruses have been posing a great threat to public health and animal industry. The developed vaccines have been widely used to reduce the risk of potential pandemic; however, the ongoing antigenic drift makes influenza virus escape from host immune response and hampers vaccine efficacy. Until now, the genetic basis of antigenic variation remains largely unknown. In this study, we used A/swine/Guangxi/18/2011 (GX/18) and A/swine/Guangdong/104/2013 (GD/104) as models to explore the molecular determinant for antigenic variation of Eurasian avian-like H1N1 (EA H1N1) swine influenza viruses (SIVs), and found that the GD/104 virus exhibited 32~64-fold lower antigenic cross-reactivity with antibodies against GX/18 virus. Therefore, we generated polyclonal antibodies against GX/18 or GD/104 virus and a monoclonal antibody (mAb), named mAb102-95, targeted to the hemagglutinin (HA) protein of GX/18 virus, and found that a single amino acid substitution at position 158 in HA protein substantially altered the antigenicity of virus. The reactivity of GX/18 virus containing G158E mutation with the mAb102-95 decreased 8-fold than that of the parental strain. Contrarily, the reactivity of GD/104 virus bearing E158G mutation with the mAb102-95 increased by 32 times as compared with that of the parental virus. Structural analysis showed that the amino acid mutation from G to E was accompanied with the R group changing from -H to -(CH ) -COOH. The induced steric effect and increased hydrophilicity of HA protein surface jointly contributed to the antigenic drift of EA H1N1 SIVs. Our study provides experimental evidence that G158E mutation in HA protein affects the antigenic property of EA H1N1 SIVs, and widens our horizon on the antigenic drift of influenza virus.

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Sowing the Seeds of a Pandemic? Mammalian Pathogenicity and Transmissibility of H1 Variant Influenza Viruses from the Swine Reservoir

Tropical Medicine and Infectious Disease ◽

10.3390/tropicalmed4010041 ◽

2019 ◽

Vol 4 (1) ◽

pp. 41 ◽

Cited By ~ 5

Author(s):

Joanna Pulit-Penaloza ◽

Jessica Belser ◽

Terrence Tumpey ◽

Taronna Maines

Keyword(s):

North American ◽

Influenza Viruses ◽

Antigenic Drift ◽

Risk Assessments ◽

Pandemic Preparedness ◽

The North ◽

Zoonotic Viruses ◽

Experimental Protocols ◽

Pandemic Strains

Emergence of genetically and antigenically diverse strains of influenza to which the human population has no or limited immunity necessitates continuous risk assessments to determine the likelihood of these viruses acquiring adaptations that facilitate sustained human-to-human transmission. As the North American swine H1 virus population has diversified over the last century by means of both antigenic drift and shift, in vivo assessments to study multifactorial traits like mammalian pathogenicity and transmissibility of these emerging influenza viruses are critical. In this review, we examine genetic, molecular, and pathogenicity and transmissibility data from a panel of contemporary North American H1 subtype swine-origin viruses isolated from humans, as compared to H1N1 seasonal and pandemic viruses, including the reconstructed 1918 virus. We present side-by-side analyses of experiments performed in the mouse and ferret models using consistent experimental protocols to facilitate enhanced interpretation of in vivo data. Contextualizing these analyses in a broader context permits a greater appreciation of the role that in vivo risk assessment experiments play in pandemic preparedness. Collectively, we find that despite strain-specific heterogeneity among swine-origin H1 viruses, contemporary swine viruses isolated from humans possess many attributes shared by prior pandemic strains, warranting heightened surveillance and evaluation of these zoonotic viruses.

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Divergent Human-Origin Influenza Viruses Detected in Australian Swine Populations

Journal of Virology ◽

10.1128/jvi.00316-18 ◽

2018 ◽

Vol 92 (16) ◽

Cited By ~ 6

Author(s):

Frank Y. K. Wong ◽

Celeste Donato ◽

Yi-Mo Deng ◽

Don Teng ◽

Naomi Komadina ◽

...

Keyword(s):

Influenza Virus ◽

Influenza A ◽

Swine Influenza ◽

Influenza Viruses ◽

Antigenic Drift ◽

Human Origin ◽

Human Influenza ◽

Influenza A Viruses ◽

Data Set ◽

Antigenic Properties

ABSTRACTGlobal swine populations infected with influenza A viruses pose a persistent pandemic risk. With the exception of a few countries, our understanding of the genetic diversity of swine influenza viruses is limited, hampering control measures and pandemic risk assessment. Here we report the genomic characteristics and evolutionary history of influenza A viruses isolated in Australia from 2012 to 2016 from two geographically isolated swine populations in the states of Queensland and Western Australia. Phylogenetic analysis with an expansive human and swine influenza virus data set comprising >40,000 sequences sampled globally revealed evidence of the pervasive introduction and long-term establishment of gene segments derived from several human influenza viruses of past seasons, including the H1N1/1977, H1N1/1995, H3N2/1968, and H3N2/2003, and the H1N1 2009 pandemic (H1N1pdm09) influenza A viruses, and a genotype that contained gene segments derived from the past three pandemics (1968, reemerged 1977, and 2009). Of the six human-derived gene lineages, only one, comprising two viruses isolated in Queensland during 2012, was closely related to swine viruses detected from other regions, indicating a previously undetected circulation of Australian swine lineages for approximately 3 to 44 years. Although the date of introduction of these lineages into Australian swine populations could not be accurately ascertained, we found evidence of sustained transmission of two lineages in swine from 2012 to 2016. The continued detection of human-origin influenza virus lineages in swine over several decades with little or unpredictable antigenic drift indicates that isolated swine populations can act as antigenic archives of human influenza viruses, raising the risk of reemergence in humans when sufficient susceptible populations arise.IMPORTANCEWe describe the evolutionary origins and antigenic properties of influenza A viruses isolated from two separate Australian swine populations from 2012 to 2016, showing that these viruses are distinct from each other and from those isolated from swine globally. Whole-genome sequencing of virus isolates revealed a high genotypic diversity that had been generated exclusively through the introduction and establishment of human influenza viruses that circulated in past seasons. We detected six reassortants with gene segments derived from human H1N1/H1N1pdm09 and various human H3N2 viruses that circulated during various periods since 1968. We also found that these swine viruses were not related to swine viruses collected elsewhere, indicating independent circulation. The detection of unique lineages and genotypes in Australia suggests that isolated swine populations that are sufficiently large can sustain influenza virus for extensive periods; we show direct evidence of a sustained transmission for at least 4 years between 2012 and 2016.

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Evolution of Novel Reassortant A/H3N2 Influenza Viruses in North American Swine and Humans, 2009–2011

Journal of Virology ◽

10.1128/jvi.00259-12 ◽

2012 ◽

Vol 86 (16) ◽

pp. 8872-8878 ◽

Cited By ~ 94

Author(s):

Martha I. Nelson ◽

Amy L. Vincent ◽

Pravina Kitikoon ◽

Edward C. Holmes ◽

Marie R. Gramer

Keyword(s):

North American ◽

Matrix Protein ◽

Age Groups ◽

Swine Influenza ◽

The United States ◽

Influenza Viruses ◽

Pandemic Threat ◽

H3n2 Influenza ◽

Na Sequences ◽

M Sequences

Novel H3N2 influenza viruses (H3N2v) containing seven genome segments from swine lineage triple-reassortant H3N2 viruses and a 2009 pandemic H1N1 (H1N1pdm09) matrix protein segment (pM) were isolated from 12 humans in the United States between August and December 2011. To understand the evolution of these novel H3N2 viruses in swine and humans, we undertook a phylogenetic analysis of 674 M sequences and 388 HA and NA sequences from influenza viruses isolated from North American swine during 2009–2011, as well as HA, NA, and M sequences from eight H3N2v viruses isolated from humans. We identified 34 swine influenza viruses (termed rH3N2p) with the same combination of H3, N2, and pM segments as the H3N2v viruses isolated from humans. Notably, these rH3N2p viruses were generated in swine via reassortment events between H3N2 viruses and the pM segment approximately 4 to 10 times since 2009. The pM segment has also reassorted with multiple distinct lineages of H1 virus, especially H1δ viruses. Importantly, the N2 segment of all H3N2v viruses isolated from humans is derived from a genetically distinct N2 lineage that has circulated in swine since being acquired by reassortment with seasonal human H3N2 viruses in 2001–2002, rather than from the N2 that is associated with the 1998 H3N2 swine lineage. The identification of this N2 variant may have implications for influenza vaccine design and the potential pandemic threat of H3N2v to human age groups with differing levels of prior exposure and immunity.

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Identification of novel human derived influenza viruses in pigs with zoonotic potential.

10.1101/2021.06.08.447649 ◽

2021 ◽

Author(s):

rodrigo tapia ◽

Barbara Brito ◽

Marco Saavedra ◽

juan mena ◽

Tamara García-Salum ◽

...

Keyword(s):

Latin America ◽

Influenza A ◽

Swine Influenza ◽

Influenza Viruses ◽

H3n2 Virus ◽

Zoonotic Potential ◽

Limited Information ◽

Global Pandemic ◽

Human Sera ◽

Antigenic Cartography

In 2009, a novel swine influenza A virus (IAV) emerged causing a global pandemic that highlighted the role of swine as a reservoir. To date, there is limited information about swine IAV circulating in Latin America. We identified two swine H1N2 and one divergent swine H3N2 viruses that co-circulated in Chilean swine together with the 2009 H1N1 pandemic strain (A(H1N1)pdm09). Phylogenetic analysis revealed several human-to-swine IAV introductions occurring as early as the mid-1980s, and since 2009, several introductions of the A(H1N1)pdm09 strain. Antigenic cartography confirmed that these viruses were antigenically unique and identified drifted variants within the clusters. Human sera from the Chilean general population showed an age-dependent mid to low-level antibody-mediated protection against swine H1N2 and A(H1N1)pdm09-like viruses and poor protection against the swine H3N2 virus, highlighting the zoonotic potential of this strain. Our results underscore the epidemiological importance of studying swine IAV in Latin America for epidemic and pandemic preparedness.

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Simultaneous infection with porcine reproductive and respiratory syndrome and influenza viruses abrogates clinical protection induced by live attenuated porcine reproductive and respiratory syndrome vaccination

10.1101/2021.08.12.456007 ◽

2021 ◽

Author(s):

Tiphany Chrun ◽

Emmanuel Atangana Maze ◽

Eleni Vatzia ◽

Veronica Martini ◽

Basu Paudyal ◽

...

Keyword(s):

Swine Influenza Virus ◽

Swine Influenza ◽

Cost Effective ◽

Influenza Viruses ◽

H3n2 Virus ◽

Economic Losses ◽

Respiratory Syndrome Virus ◽

Upper Respiratory Tract ◽

Live Virus ◽

Clinical Protection

The porcine respiratory disease complex (PRDC) is responsible for significant economic losses in the pig industry worldwide. Porcine reproductive and respiratory syndrome virus (PRRSV) and swine influenza virus are major viral contributors to PRDC. Vaccines are cost-effective measures for controlling PRRS, however, their efficacy in the context of co-infections has been poorly investigated. In this study, we aimed to determine the effect of PRRSV-2 and swine influenza H3N2 virus co-infection on the efficacy of PRRSV modified live virus (MLV) vaccination, which is widely used in the field. Following simultaneous challenge with contemporary PRRSV-2 and H3N2 field isolates, we found that the protective effect of PRRS MLV vaccination on clinical disease and pathology was abrogated, although viral load was unaffected and antibody responses were enhanced. In contrast, co-infection in non-immunized animals reduced PRRSV-2 viremia and H3N2 virus load in the upper respiratory tract and potentiated T cell responses against both PRRSV-2 and H3N2 in the lung. Further analysis suggested that an upregulation of inhibitory cytokines gene expression in the lungs of vaccinated pigs may have influenced responses to H3N2 and PRRSV-2. These findings provide important insights into the effect of viral co-infections on PRRS vaccine efficacy that may help identity more effective vaccination strategies against PRDC in the field.

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North American Triple Reassortant and Eurasian H1N1 Swine Influenza Viruses Do Not Readily Reassort to Generate a 2009 Pandemic H1N1-Like Virus

mBio ◽

10.1128/mbio.00919-13 ◽

2014 ◽

Vol 5 (2) ◽

Cited By ~ 11

Author(s):

Wenjun Ma ◽

Qinfang Liu ◽

Chuanling Qiao ◽

Gustavo del Real ◽

Adolfo García-Sastre ◽

...

Keyword(s):

Cell Cultures ◽

North American ◽

Influenza A ◽

H1n1 Virus ◽

Rare Event ◽

Swine Influenza ◽

Influenza Viruses ◽

Pandemic H1n1 ◽

Continuous Cell Lines ◽

Reassortant Viruses

ABSTRACTThe 2009 pandemic H1N1 virus (pH1N1) was derived through reassortment of North American triple reassortant and Eurasian avian-like swine influenza viruses (SIVs). To date, when, how and where the pH1N1 arose is not understood. To investigate viral reassortment, we coinfected cell cultures and a group of pigs with or without preexisting immunity with a Eurasian H1N1 virus, A/Swine/Spain/53207/2004 (SP04), and a North American triple reassortant H1N1 virus, A/Swine/Kansas/77778/2007 (KS07). The infected pigs were cohoused with one or two groups of contact animals to investigate viral transmission. In coinfected MDCK or PK15 continuous cell lines with KS07 and SP04 viruses, more than 20 different reassortant viruses were found. In pigs without or with preexisting immunity (immunized with commercial inactivated swine influenza vaccines) and coinfected with both viruses, six or seven reassortant viruses, as well as the parental viruses, were identified in bronchoalveolar lavage fluid samples from the lungs. Interestingly, only one or two viruses transmitted to and were detected in contact animals. No reassortant containing a gene constellation similar to that of pH1N1 virus was found in either coinfected cells or pigs, indicating that the reassortment event that resulted in the generation of this virus is a rare event that likely involved specific viral strains and/or a favorable, not-yet-understood environment.IMPORTANCEThe 2009 pandemic-like H1N1 virus could not be reproduced either in cell cultures or in pigs coinfected with North American triple reassortant H1N1 and Eurasian H1N1 swine influenza viruses. This finding suggests that the generation of the 2009 pandemic H1N1 virus by reassortment was a rare event that likely involved specific viral strains and unknown factors. Different reassortant viruses were detected in coinfected pigs with and without preexisting immunity, indicating that host immunity plays a relevant role in driving viral reassortment of influenza A virus.

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