Airborne Transmission of Influenza A/H5N1 Virus Between Ferrets

TLDR

Highly pathogenic avian influenza A/H5N1 can cause severe disease in humans but has not yet been shown to transmit via aerosol or respiratory droplets between humans. The study aimed to determine whether A/H5N1 could acquire airborne transmissibility under natural conditions. The authors genetically modified A/H5N1 by site‑directed mutagenesis and serially passaged it in ferrets to test this possibility. The modified virus acquired mutations, became airborne transmissible in ferrets, caused no deaths, consistently carried four HA and one PB2 substitutions, remained oseltamivir‑sensitive, and reacted with antisera, proving that A/H5N1 can gain airborne transmission between mammals without intermediate host recombination and thus poses a pandemic risk.

Abstract

Highly pathogenic avian influenza A/H5N1 virus can cause morbidity and mortality in humans but thus far has not acquired the ability to be transmitted by aerosol or respiratory droplet ("airborne transmission") between humans. To address the concern that the virus could acquire this ability under natural conditions, we genetically modified A/H5N1 virus by site-directed mutagenesis and subsequent serial passage in ferrets. The genetically modified A/H5N1 virus acquired mutations during passage in ferrets, ultimately becoming airborne transmissible in ferrets. None of the recipient ferrets died after airborne infection with the mutant A/H5N1 viruses. Four amino acid substitutions in the host receptor-binding protein hemagglutinin, and one in the polymerase complex protein basic polymerase 2, were consistently present in airborne-transmitted viruses. The transmissible viruses were sensitive to the antiviral drug oseltamivir and reacted well with antisera raised against H5 influenza vaccine strains. Thus, avian A/H5N1 influenza viruses can acquire the capacity for airborne transmission between mammals without recombination in an intermediate host and therefore constitute a risk for human pandemic influenza.