Understanding the Origins of a Pandemic Virus

Understanding the origin of infectious diseases provides scientifically based rationales for implementing public health measures that may help to avoid or mitigate future epidemics. The recent ancestors of a pandemic virus provide invaluable information about the set of minimal genomic alterations that transformed a zoonotic agent into a full human pandemic. Since the first confirmed cases of the H1N1 pandemic virus in the spring of 2009 , several hypotheses about the strain's origins have been proposed. However, how, where, and when it first infected humans is still far from clear. The only way to piece together this epidemiological puzzle relies on the collective effort of the international scientific community to increase genomic sequencing of influenza isolates, especially ones collected in the months prior to the origin of the pandemic. The H1N1 pandemic in 2009 was the first influenza pandemic of the 21 century, a period in which technological developments have allowed scientists around the globe to isolate and sequence viral genomes and share results in almost real time. These advances present an opportunity to learn how influenza pandemics start, spread and evolve. Despite all the worldwide effort, there are many questions that remain unanswered about the origin of the 2009 H1N1 influenza virus (H1N1pdm). The closest ancestors of the pandemic virus were related to viruses isolated in swine more than a decade ago , but it is still unclear how, where, and when it became a human pandemic, and where the virus was circulating the year before the pandemic was declared. The most accepted conjecture is the “hidden pig herd hypothesis,” which suggests that incomplete surveillance missed strains circulating in unsampled swine herds . Since March 2009, when the first pandemic cases were reported, until May 1, 2009, hundreds of H1N1pdm isolates were collected and sequenced, all of which came from human hosts except for one isolate from a pig in Mexico (A/swine/4/Mexico/2009 (H1N1)). After May 1, 2009, more than one hundred H1N1pdm virus sequences isolated in swine have been deposited in the National Center for Biotechnology Information Influenza Virus Resource, all of which could be traced back to human H1N1pdm viruses, hinting at a possible human to swine transmission, with no evidence of swine to human transmission. Although, GenBank also contains more than a hundred swine influenza genomes, isolated from three continents prior the start of the pandemic (between 2008 and the spring of 2009), none seem directly related to the H1N1pdm pandemic virus. It is indeed surprising that only one H1N1pdm swine isolate is publically known before the pandemic virus was widely spread in the human