Influenza A Viruses of Human Origin in Swine, Brazil - Volume 21, Number 8—August 2015 - Emerging Infectious Disease journal - CDC

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Influenza A Viruses of Human Origin in Swine, Brazil - Volume 21, Number 8—August 2015 - Emerging Infectious Disease journal - CDC

Volume 21, Number 8—August 2015

Research

Influenza A Viruses of Human Origin in Swine, Brazil

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• Methods
• Results
• Discussion
• Suggested Citation

Figures

• Figure 1
• Figure 2
• Figure 3
• Figure 4

Tables

• Table 1
• Table 2

Technical Appendicies

• Technical Appendix

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Martha I. Nelson1 , Rejane Schaefer1, Danielle Gava, Maurício Egídio Cantão, and Janice Reis Ciacci-Zanella

Author affiliations: Fogarty International Center of the National Institutes of Health, Bethesda, Maryland, USA (M.I. Nelson); EMBRAPA Swine and Poultry, Concordia, Brazil (R. Schaefer, D. Gava, M.E. Cantão, J.R. Ciacci-Zanella)

Suggested citation for this article

Abstract

The evolutionary origins of the influenza A(H1N1)pdm09 virus that caused the first outbreak of the 2009 pandemic in Mexico remain unclear, highlighting the lack of swine surveillance in Latin American countries. Although Brazil has one of the largest swine populations in the world, influenza was not thought to be endemic in Brazil’s swine until the major outbreaks of influenza A(H1N1)pdm09 in 2009. Through phylogenetic analysis of whole-genome sequences of influenza viruses of the H1N1, H1N2, and H3N2 subtypes collected in swine in Brazil during 2009–2012, we identified multiple previously uncharacterized influenza viruses of human seasonal H1N2 and H3N2 virus origin that have circulated undetected in swine for more than a decade. Viral diversity has further increased in Brazil through reassortment between co-circulating viruses, including A(H1N1)pdm09. The circulation of multiple divergent hemagglutinin lineages challenges the design of effective cross-protective vaccines and highlights the need for additional surveillance.

Influenza A viruses circulating in swine (swIAVs) are of major economic concern for the swine industry and a pandemic threat for humans. The H1N1 influenza pandemic of 2009 was associated with a virus of swine origins (1) that caused its first outbreak in humans in Mexico in early 2009 (2). However, the evolutionary origins of influenza A(H1N1)pdm09 (pH1N1) virus in swine are poorly understood, and no potential progenitor viruses have been detected in swine in any part of the world. The relatively small number of swIAVs that have been characterized in Latin America make it particularly difficult to confirm or negate the possibility of pH1N1 evolving in swine in Mexico or another Latin American country before emergence in humans.

Figure 1. Areas of swine production in 7 states in southern, midwestern, and southeastern Brazil: Rio Grande do Sul (RS) State (total swine population ≈7.0 million), Santa Catarina (SC) State (≈9.0 million swine),...

Since 2009, transmission of pH1N1 virus from humans to pigs has been documented in numerous countries spanning 6 continents (3–13), including many countries where influenza viruses previously had not been detected in swine, such as Australia (14), Finland (15), and Cameroon (16). pH1N1 virus has been identified in swine in several Latin American countries, including Argentina (17), Brazil (18,19), Colombia (20), and Mexico (21), because of human-to-swine transmission events that have occurred since 2009. In Argentina, multiple subtypes of viruses of human seasonal virus origin also have been identified in swine (22). Although Brazil hosts one of the largest swine populations in the world (≈41 million hogs), little evidence existed of swIAV circulation in swine herds in Brazil before 2009 (23–25). Influenza virus in pigs was first detected in Brazil in 1974, and the isolated virus was closely related to the classical North American swine virus A/swine/Illinois/1/63/H1N1 (24). However, relatively little clinical illness was observed in pigs in Brazil until 2009. Since 2009, Brazil’s swine population has experienced outbreaks of pH1N1 that are associated with respiratory illness. These outbreaks have been located primarily in the country’s major swine production regions in southern, midwestern, and southeastern Brazil (Figure 1). As a result, surveillance efforts for IAVs in swine populations in Brazil have increased, revealing additional influenza virus diversity. Serum collected from swine in southeastern Brazil during January–March 2009 indicated the widespread presence of antibodies cross-reactive to multiple antigenically distinct subtypes in swine: North American classical swine H1N1 (44.4%), North American triple-reassortant swine H3N2 (23.5%), and human-like H1N1 (38.3%) (25). In southern Brazil, the seroprevalence of the H3N2 subtype was recently found to be ≈20% (23). A human-like H1N2 virus was isolated from captive wild boars (26) and from swine (27) in Brazil.

Here, a phylogenetic analysis of newly sequenced influenza viruses from Brazil’s swine herds provides evidence that multiple IAVs of human seasonal virus origin have been circulating in swine for more than a decade. These particular H3N2 and H1N2 swIAV clades appear to be specific to Brazil. The co-circulation of multiple genetically diverse swIAV lineages of the H1N1, H1N2, and H3N2 subtypes introduces new challenges for the control of influenza in Brazil’s swine herds, including development of cross-protective vaccines.

Dr. Nelson is a Research Fellow at the Division of International Epidemiology and Population Studies at the Fogarty International Center, National Institutes of Health. Her primary research interests are the evolutionary dynamics of influenza viruses and other emerging pathogens.

Acknowledgments

We thank Neide L. Simon and Marisete F. Schiochet for assistance with laboratory techniques and Laboratório Multiusuários Centralizado de Genômica Funcional Aplicada à Agropecuária e Agroenergia for IAV sequencing using the Illumina platform.

This work was financially supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq process no. 578102/2008-0) and EMBRAPA. This work was supported in part by the Multinational Influenza Seasonal Mortality Study, an ongoing international collaborative effort to understand influenza epidemiology and evolution, led by the Fogarty International Center, National Institutes of Health, with funding from Office of Pandemics and Emerging Threats at the US Department of Health and Human Services.

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Figures

• Figure 1. Areas of swine production in 7 states in southern, midwestern, and southeastern Brazil: Rio Grande do Sul (RS) State (total swine population ≈7.0 million), Santa Catarina (SC) State (≈9.0...
• Figure 2. Phylogenetic relationships between human and swine influenza H3 segments. Time-scaled Bayesian maximum clade credibility (MCC) tree inferred for the hemagglutinin (H3) sequences of 463 viruses, including 4 viruses sequenced...
• Figure 3. Phylogenetic relationships between human and swine influenza H1 segments. Time-scaled Bayesian maximum clade credibility (MCC) tree inferred for the hemagglutinin (H1) sequences of 209 viruses, including 2 swine viruses...
• Figure 4. Phylogenetic relationships between human and swine influenza N2 segments. Time-scaled Bayesian maximum clade credibility (MCC) tree inferred for the neuraminidase (N2) sequences of 682 viruses, including 6 swine viruses...

Tables

• Table 1. Characteristics and phylogenetic position of 16 influenza A viruses from swine sequenced at EMBRAPA (Brazilian Agricultural Research Corporation)
• Table 2. Introductions of influenza A(H1N1)pdm09 virus from humans to swine in Latin America

Technical Appendix

• Technical Appendix. GenBank accession numbers for 16 swine influenza viruses from Brazil; and maximum-likelihood trees of human and swine H3, H1, N2, pandemic H1, pandemic N1, pandemic PB2, and pandemic matrix... 18.90 MB

Suggested citation for this article: Nelson MI, Schaefer R, Gava D, Cantão ME, Ciacci-Zanella JR. Influenza A viruses of human origin in swine, Brazil. Emerg Infect Dis. 2015 Aug [date cited]. http://dx.doi.org/10.3201/eid2108.141891

DOI: 10.3201/eid2108.141891

1These authors contributed equally to this article.