Origins of the 2009 H1N1 influenza pandemic in swine in Mexico

• Published in: eLife Vol. 5
• Main Authors: Mena, Ignacio, Nelson, Martha I, Quezada-Monroy, Francisco, Dutta, Jayeeta, Cortes-Fernández, Refugio, Lara-Puente, J Horacio, Castro-Peralta, Felipa, Cunha, Luis F, Trovão, Nídia S, Lozano-Dubernard, Bernardo, Rambaut, Andrew, van Bakel, Harm, García-Sastre, Adolfo
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 28.06.2016; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: 2009 pandemic; Animals; Diseases; Epidemics; Epidemiology; Epidemiology and Global Health; evolution; Evolution, Molecular; Fisheries; Genetic diversity; Genomes; Genotype & phenotype; Health surveillance; Hogs; Humans; Immunology; Influenza A; influenza A virus; Influenza A Virus, H1N1 Subtype - classification; Influenza A Virus, H1N1 Subtype - genetics; Influenza A Virus, H1N1 Subtype - isolation & purification; Influenza viruses; Influenza, Human - epidemiology; Influenza, Human - virology; Medicine; Mexico; Microbiology and Infectious Disease; Origin; Orthomyxoviridae Infections - veterinary; Orthomyxoviridae Infections - virology; Pandemics; phylogeography; Rural development; Sequence Analysis, DNA; Swine; Swine Diseases - epidemiology; Swine Diseases - virology; Swine flu; Viruses; Zoonoses; Zoonoses - epidemiology; Zoonoses - virology; zoonosis; Mexico; Hong Kong China; United States > US; Asia; global health; swine; epidemiology; infectious disease; 2009 pandemic; microbiology; evolution; virus; zoonosis; influenza A virus; phylogeography
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.16777

Asia is considered an important source of influenza A virus (IAV) pandemics, owing to large, diverse viral reservoirs in poultry and swine. However, the zoonotic origins of the 2009 A/H1N1 influenza pandemic virus (pdmH1N1) remain unclear, due to conflicting evidence from swine and humans. There is strong evidence that the first human outbreak of pdmH1N1 occurred in Mexico in early 2009. However, no related swine viruses have been detected in Mexico or any part of the Americas, and to date the most closely related ancestor viruses were identified in Asian swine. Here, we use 58 new whole-genome sequences from IAVs collected in Mexican swine to establish that the swine virus responsible for the 2009 pandemic evolved in central Mexico. This finding highlights how the 2009 pandemic arose from a region not considered a pandemic risk, owing to an expansion of IAV diversity in swine resulting from long-distance live swine trade. In 2009 a new influenza virus jumped from pigs to humans and spread very rapidly, causing an initial outbreak in Mexico and becoming a global pandemic in just a few months. Although the most straightforward explanation is that the virus originated in swine in Mexico, several studies suggested that this was unlikely because key genetic components of the virus had never been detected in the Americas. Determining the source of the disease is critical for predicting and preparing for future influenza pandemics. Mena, Nelson et al. sought to better characterize the genetic diversity of influenza viruses in Mexican swine by obtaining the entire genetic sequences of 58 viruses collected from swine in Mexico, including some from previously unsampled regions in central Mexico. The sequences revealed extensive diversity among the influenza viruses circulating in Mexican swine. Several viruses included genetic segments that originated from viruses from Eurasia (the landmass containing Europe and Asia) and had not previously been detected in the Americas. The new sequences contained key genetic components of the 2009 pandemic virus. Furthermore, the sequences suggest that viruses with a similar genetic composition to the 2009 pandemic virus have been circulating in pigs in central-west Mexico for more than a decade. Thus, this region is the most likely source of the virus that started the 2009 pandemic. Mena, Nelson et al. also found that the movement of viruses from Eurasia and the United States into Mexico closely follows the direction of the global trade of live swine. This highlights the critical role that animal trading plays in bringing together diverse viruses from different continents, which can then combine and generate new pandemic viruses. A potential next step is to perform experiments that investigate how well the swine viruses can replicate and pass between different animal models. Comparing the results of such experiments with the findings presented by Mena, Nelson et al. could identify factors that make the viruses more likely to spread to humans and produce a pandemic.