Limited airborne transmission of H7N9 influenza A virus between ferrets

• Published in: Nature (London) Vol. 501; no. 7468; pp. 560 - 563
• Main Authors: Richard, Mathilde, Schrauwen, Eefje J. A., de Graaf, Miranda, Bestebroer, Theo M., Spronken, Monique I. J., van Boheemen, Sander, de Meulder, Dennis, Lexmond, Pascal, Linster, Martin, Herfst, Sander, Smith, Derek J., van den Brand, Judith M., Burke, David F., Kuiken, Thijs, Rimmelzwaan, Guus F., Osterhaus, Albert D. M. E., Fouchier, Ron A. M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.09.2013; Nature Publishing Group
• Subjects: 631/326/596/1578; Air Microbiology; Animals; Avian flu; Avian influenza; Avian influenza viruses; Birds - virology; Cercopithecus aethiops; Cloning; Development and progression; Disease transmission; Distribution; Dogs; Epidemics; Ferrets; Ferrets - virology; Genetic variance; Genome, Viral - genetics; Harbors; Health aspects; Hemagglutinin Glycoproteins, Influenza Virus - chemistry; Humanities and Social Sciences; Humans; Immunization; Influenza A virus - chemistry; Influenza A virus - classification; Influenza A virus - genetics; Influenza A virus - pathogenicity; Influenza in Birds - transmission; Influenza in Birds - virology; Influenza, Human - transmission; Influenza, Human - virology; letter; Madin Darby Canine Kidney Cells; Models, Molecular; multidisciplinary; Observations; Orthomyxoviridae Infections - transmission; Orthomyxoviridae Infections - virology; Pandemics; Public health; Respiratory diseases; Respiratory distress syndrome; Risk factors; Science; United States; Vero Cells; Viruses; Waterfowl; Netherlands; United States
• ISSN: 0028-0836; 1476-4687; 1476-4687
• DOI: 10.1038/nature12476

An investigation into the transmissibility of the H7N9 influenza A virus in ferrets finds that although the virus has some determinants associated with human adaptation and transmissibility between mammals, the airborne transmission between ferrets is limited. Transmission of emerging H7N9 virus By 20 July 2013, there had been 134 laboratory-confirmed human cases of infection with avian influenza A H7N9 virus infection, including 43 deaths. Yoshihiro Kawaoka and colleagues characterize the biology of two recent isolates of the virus. They provide a wealth of data from infections in mice, pigs, macaques and ferrets. H7N9 virus is shown to be less sensitive to neuraminidase inhibitors than pandemic H1N1 virus, but equally susceptible to an experimental polymerase inhibitor. Terrence Tumpey and colleagues determine the capacity of two clinical H7N9 isolates to cause disease and transmit between mammals. They show that the virus can replicate in human airway cells and in the respiratory tract of ferrets to a higher level than can seasonal H3N2 virus, and show higher lethality in mice than genetically related H7N9 and H9N2 viruses. In transmission studies, the H7N9 virus showed limited transmission in ferrets by respiratory droplets. Ron Fouchier and colleagues investigate the transmissibility of H7N9 virus between ferrets. They show that airborne transmission can occur, but inefficiently. They also show that on passage in ferrets, virus variants that have higher avian receptor binding, higher pH of fusion and lower thermostability are selected, and they suggest that these characteristics may result in reduced transmissibility. Wild waterfowl form the main reservoir of influenza A viruses, from which transmission occurs directly or indirectly to various secondary hosts, including humans 1 . Direct avian-to-human transmission has been observed for viruses of subtypes A(H5N1), A(H7N2), A(H7N3), A(H7N7), A(H9N2) and A(H10N7) upon human exposure to poultry 2 , 3 , 4 , 5 , 6 , 7 , but a lack of sustained human-to-human transmission has prevented these viruses from causing new pandemics. Recently, avian A(H7N9) viruses were transmitted to humans, causing severe respiratory disease and deaths in China 8 . Because transmission via respiratory droplets and aerosols (hereafter referred to as airborne transmission) is the main route for efficient transmission between humans, it is important to gain an insight into airborne transmission of the A(H7N9) virus. Here we show that although the A/Anhui/1/2013 A(H7N9) virus harbours determinants associated with human adaptation and transmissibility between mammals, its airborne transmissibility in ferrets is limited, and it is intermediate between that of typical human and avian influenza viruses. Multiple A(H7N9) virus genetic variants were transmitted. Upon ferret passage, variants with higher avian receptor binding, higher pH of fusion, and lower thermostability were selected, potentially resulting in reduced transmissibility. This A(H7N9) virus outbreak highlights the need for increased understanding of the determinants of efficient airborne transmission of avian influenza viruses between mammals.