The Potential for Respiratory Droplet–Transmissible A/H5N1 Influenza Virus to Evolve in a Mammalian Host

TLDR

Avian A/H5N1 influenza viruses pose a pandemic threat, and as few as five amino acid substitutions—or four with reassortment—could enable mammal‑to‑mammal respiratory droplet transmission. We used a mathematical model of within‑host virus evolution to study factors that could increase or decrease the probability of the remaining substitutions evolving after infection of a mammalian host. Surveillance shows two of the key substitutions are already common, so some A/H5N1 strains may need only three more changes to become transmissible between mammals; combined with other factors, this makes natural evolution a serious threat, underscoring the need for more data to assess and potentially avert it.

Abstract

Avian A/H5N1 influenza viruses pose a pandemic threat. As few as five amino acid substitutions, or four with reassortment, might be sufficient for mammal-to-mammal transmission through respiratory droplets. From surveillance data, we found that two of these substitutions are common in A/H5N1 viruses, and thus, some viruses might require only three additional substitutions to become transmissible via respiratory droplets between mammals. We used a mathematical model of within-host virus evolution to study factors that could increase and decrease the probability of the remaining substitutions evolving after the virus has infected a mammalian host. These factors, combined with the presence of some of these substitutions in circulating strains, make a virus evolving in nature a potentially serious threat. These results highlight critical areas in which more data are needed for assessing, and potentially averting, this threat.