H7N9 Influenza Viruses Are Transmissible in Ferrets by Respiratory Droplet

H7N9 Adaptation Puzzling and alarming reports of an outbreak in early 2013 of human infections by a low-pathogenicity avian influenza virus has rocked the poultry industry in central eastern China and brought fears of initiating a human pandemic. Over 130 human cases have been reported with 37 deaths until closure of poultry markets accompanied a near-cessation of human case reports. From surveillance sampling of >10,000 isolates obtained during April 2013, Zhang et al. (p. 410, published online 18 July) took 37 isolates of avian origin H7N9 and compared them to human H7N9 isolates. The majority of H7N9 isolates came from live poultry markets, although some originated in pigeons. Sequence analysis indicated that the chicken isolates had retained the avian characteristics at sites on the influenza genes for PB2 and the surface hemagglutinin HA, where adaptive mutations have been observed before. Sequence analysis also showed a higher variability in the internal genes than in HA and neuraminidase NA. By using glycan arrays, it was shown that avian and human isolates bound to human, but also to some extent to avian, receptors. As expected, the virus replicated well in chickens without causing disease, whereas in mice only the human isolates were highly pathogenic. The human virus, but not the avian, transmitted between ferrets through the air. A large survey of H7N9 influenza viruses in China reveals a spectrum of mutation and virulence. A newly emerged H7N9 virus has caused 132 human infections with 37 deaths in China since 18 February 2013. Control measures in H7N9 virus–positive live poultry markets have reduced the number of infections; however, the character of the virus, including its pandemic potential, remains largely unknown. We systematically analyzed H7N9 viruses isolated from birds and humans. The viruses were genetically closely related and bound to human airway receptors; some also maintained the ability to bind to avian airway receptors. The viruses isolated from birds were nonpathogenic in chickens, ducks, and mice; however, the viruses isolated from humans caused up to 30% body weight loss in mice. Most importantly, one virus isolated from humans was highly transmissible in ferrets by respiratory droplet. Our findings indicate nothing to reduce the concern that these viruses can transmit between humans.

[1]  Tian Bai,et al.  Preliminary Report: Epidemiology of the Avian Influenza A (H7N9) Outbreak in China , 2013 .

[2]  Wenjun Song,et al.  Human infections with the emerging avian influenza A H7N9 virus from wet market poultry: clinical analysis and characterisation of viral genome , 2013, The Lancet.

[3]  J. Paulson,et al.  Receptor determinants of human and animal influenza virus isolates: differences in receptor specificity of the H3 hemagglutinin based on species of origin. , 1983, Virology.

[4]  Weizhong Yang,et al.  Epidemiology of human infections with avian influenza A(H7N9) virus in China. , 2014, The New England journal of medicine.

[5]  Gabriele Neumann,et al.  Experimental adaptation of an influenza H5 haemagglutinin (HA) confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets , 2012, Nature.

[6]  Guohua Deng,et al.  H5N1 Hybrid Viruses Bearing 2009/H1N1 Virus Genes Transmit in Guinea Pigs by Respiratory Droplet , 2013, Science.

[7]  R. Webster,et al.  Molecular Basis of Replication of Duck H5N1 Influenza Viruses in a Mammalian Mouse Model , 2005, Journal of Virology.

[8]  G. Neumann,et al.  Genetic analysis of novel avian A(H7N9) influenza viruses isolated from patients in China, February to April 2013. , 2013, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[9]  Louise Taylor,et al.  OIE Manual of Diagnostic Tests and Vaccines for Terrestrial Animals , 2014 .

[10]  Zejun Li,et al.  Identification of Amino Acids in HA and PB2 Critical for the Transmission of H5N1 Avian Influenza Viruses in a Mammalian Host , 2009, PLoS pathogens.

[11]  K. Lindblade,et al.  A distinct lineage of influenza A virus from bats , 2012, Proceedings of the National Academy of Sciences.

[12]  Ian A. Wilson,et al.  A Single Amino Acid Substitution in 1918 Influenza Virus Hemagglutinin Changes Receptor Binding Specificity , 2005, Journal of Virology.

[13]  David E. Swayne,et al.  A Two-Amino Acid Change in the Hemagglutinin of the 1918 Influenza Virus Abolishes Transmission , 2007, Science.

[14]  Hualan Chen,et al.  Isolation and characterization of H7N9 viruses from live poultry markets — Implication of the source of current H7N9 infection in humans , 2013 .

[15]  Adolfo García-Sastre,et al.  The guinea pig as a transmission model for human influenza viruses. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[16]  Y. Kawaoka,et al.  The Role of Influenza A Virus Hemagglutinin Residues 226 and 228 in Receptor Specificity and Host Range Restriction , 1998, Journal of Virology.

[17]  Hualan Chen,et al.  Continued Evolution of H5N1 Influenza Viruses in Wild Birds, Domestic Poultry, and Humans in China from 2004 to 2009 , 2010, Journal of Virology.

[18]  Y. Kawaoka,et al.  Key Molecular Factors in Hemagglutinin and PB2 Contribute to Efficient Transmission of the 2009 H1N1 Pandemic Influenza Virus , 2012, Journal of Virology.

[19]  G. Kochs,et al.  Oseltamivir-Resistant Variants of the 2009 Pandemic H1N1 Influenza A Virus Are Not Attenuated in the Guinea Pig and Ferret Transmission Models , 2010, Journal of Virology.

[20]  Jie Dong,et al.  Human Infection with a Novel Avian-Origin Influenza A (H7N9) Virus. , 2018 .

[21]  Yoshihiro Kawaoka,et al.  Molecular Basis for High Virulence of Hong Kong H5N1 Influenza A Viruses , 2001, Science.

[22]  Yoshihiro Kawaoka,et al.  Early Alterations of the Receptor-Binding Properties of H1, H2, and H3 Avian Influenza Virus Hemagglutinins after Their Introduction into Mammals , 2000, Journal of Virology.

[23]  N. Cox,et al.  A Mouse Model for the Evaluation of Pathogenesis and Immunity to Influenza A (H5N1) Viruses Isolated from Humans , 1999, Journal of Virology.

[24]  B. Murphy,et al.  A single amino acid in the PB2 gene of influenza A virus is a determinant of host range , 1993, Journal of virology.

[25]  Theo M Bestebroer,et al.  Airborne Transmission of Influenza A/H5N1 Virus Between Ferrets , 2012, Science.