Novel Swine Influenza Virus Has 'Pandemic Potential'

February 27, 2012 — A novel strain of a swine influenza virus that sickened just 12 individuals in 2011 nevertheless merits continued surveillance because tests indicate that the emerging virus has "pandemic potential" among humans, according to an article published online February 21 in the Proceedings of the National Academy of Sciences. In the tests, ferrets were inoculated with isolates of this novel virus, as well as earlier versions. The viruses efficiently replicated and spread among the ferrets, which resemble humans in terms of lung physiology and susceptibility to influenza viruses, lead author Melissa Pearce, PhD, an associate service fellow at the US Centers for Disease Control and Prevention (CDC), and coauthors write. The swine influenza virus from 2011 is designated A(H3N2)v, with the "v" standing for variant. What accounts for the variance in this particular virus is a gene from the pandemic 2009 influenza A(H1N1) virus that codes for matrix proteins in the viral shell. Seasonal human influenza strains now in circulation include an A(H3N2) virus, as well as the pandemic 2009 A(H1N1) virus. The current trivalent influenza vaccine guards against both of these viruses in addition to an influenza B strain. However, Dr. Pearce and colleagues write that the swine influenza variant is antigenetically distinct from the current human A(H3N2) virus, and therefore "would not be well covered by the current trivalent vaccine." With that limitation in mind, the CDC has already embarked on developing a vaccine for the A(H3N2)v virus from 2011 in case it should begin to spread among humans on a sustained basis. Virus Give-and-Take Between Humans and Pigs The article by Dr. Pearce and 12 other authors traces a convoluted history of the novel virus that has rung alarm bells. The human A(H3N2) virus, they write, infected pigs in the late 1990s and spread widely through North American herds. In turn, variations of this now-swine influenza virus, all of which were designated A(H3N2)v, infected a smattering of humans, including 5 individuals in 2010. Four of the 5 people infected either had direct contact with pigs or lived close to pig farms. One of those individuals apparently passed the virus to his child. All 5 recovered, although 2 patients required hospitalization. The CDC identified 12 individuals in 2011 who were infected with a swine-origin A(H3N2)v virus with a twist not seen in the previous cases: The 2011 version contained a matrix gene from the pandemic 2009 influenza A(H1N1) virus, which had made its way into pigs as well. These 12 infected individuals, all but 1 of them children, were scattered across 5 states. Similar to the 5 patients in 2010, they all recovered, although 3 were hospitalized. The symptoms and severity of their influenza resembled that of the seasonal variety, according to the CDC. What worries the CDC is that, as in 2010, some of the 12 individuals in 2011 apparently caught the A(H3N2)v virus from another person, as opposed to from a pig. Human-to-human transmission was limited, but the agency notes that influenza viruses can mutate into more easily spread forms. Ferreting Out the Viral Truth To delve into the question of pandemic potential, Dr. Pearce and coauthors analyzed the virulence, transmissibility, and receptor-binding preferences of 4 A(H3N2)v viruses isolated from human subjects: 1 from 2009, 2 from 2010, and 1 from 2011. After inoculating ferrets with the isolates, they found that: •All 4 viruses replicated efficiently in a ferret's upper respiratory tract. •Inoculated ferrets lost 8% to 10% of their weight and developed a fever. Their lymphocyte count temporarily fell by 13% to 24%. In contrast, infection with a "highly pathogenic" avian influenza virus can reduce lymphocyte counts by more than 20%. •All 4 A(H3N2)v viruses spread efficiently among ferrets in the same cage. •When ferrets were separated by perforated walls, the swine influenza viruses from 2010 and 2011 also spread efficiently by respiratory droplets, in contrast with the less efficient 2009 virus. The researchers also inoculated cultures of human airway epithelial cells with the 4 A(H3N2)v viruses, along with seasonal human A(H3N2) viruses. All 4 of the swine-origin variants replicated to higher levels than their seasonal human virus counterparts. In a glycan array analysis, the viruses from 2009 and 2010 exhibited binding characteristics similar to those of seasonal human influenza A viruses, suggesting that they, too, would replicate handily in the upper respiratory tract of humans. "These findings," the authors write, "underscore the need for continued surveillance and characterization of these viruses because they resemble viruses with pandemic potential." The authors note that it is unclear whether the matrix gene from the pandemic A(H1N1) virus found in the swine-origin A(H3N2)v virus from 2011 improves its ability to spread in pigs and infect humans. Although some have suggested that the matrix segment of the pandemic human virus enhances respiratory-droplet transmission in a guinea pig model, the isolate viruses from 2010 without that matrix segment spread among ferrets just as easily as the 2011 version. The authors have disclosed no relevant financial relationships.