Mammalian adaptation of influenza A (H7N9) virus is limited by a narrow genetic bottleneck

NIAID CEIRS | Research Publication Commentary

Zaraket, H et al. Mammalian adaptation of influenza A (H7N9) virus is limited by a narrow genetic bottleneck. Nat Commun. 2015 Apr 8.

Human infections with avian influenza pose a public health risk because they signify the ability of an avian-adapted virus to cross the species barrier and become a potential pandemic threat. Although human infection with avian influenza can be serious and even deadly, infections typically occur only when humans are in close contact with birds.

In February and March of 2013, avian influenza A (H7N9) virus crossed the species barrier and infected humans exposed in live bird markets. Human infections have continued to be reported in the 2013-2014 and 2014-2015 winter seasons following the initial outbreak. For humans, the H7N9 avian influenza strain is unusually dangerous with a 30% mortality rate. However, H7N9 does not cause severe disease in poultry, and humans in close contact with birds may be exposed without knowing the birds are infected. Although transmission of the virus has been reported among close contacts, human-to-human transmission has not been sustained. In this paper, Dr. Hassan Zaraket and the research team examine the transmission dynamics of H7N9 in chickens and ferrets and offer an explanation for why transmission has not been sustained in the mammalian-adapted virus.

Genetic diversity of a virus is an important component for successful adaptation to a new host. Greater genetic diversity of a virus population results in a higher probability of mutations that favor infection, replication, and transmission in the new species. While H7N9 has shown the ability to infect both ferrets and humans, the authors suggest a bottleneck, or lack of genetic diversity, in the infected animals prevents the virus from readily acquiring additional mutations that promote transmission within the new species. A comparison of the genetic diversity generated during H7N9 replication in chickens and ferrets support this theory. Zaraket and colleagues show that chickens display a high level of genetic diversity of H7N9 virus and can readily transmit the virus, while ferrets show limited diversity and poor transmissibility. The set of mutations that allow infection of the ferret appear to be incompatible with efficient ferret-to-ferret transmission.

While this study suggests that a lack of genetic diversity limits mammalian adaptation of influenza A (H7N9), this bottleneck does not completely eliminate the risk of mammalian adaptation. Given that sustained human-to-human transmission of avian influenza has pandemic potential, the authors emphasize the need for continued research and vigilance.