Human Infection with a Novel Avian-Origin Influenza A (H7N9) Virus.

BACKGROUND Infection of poultry with influenza A subtype H7 viruses occurs worldwide, but the introduction of this subtype to humans in Asia has not been observed previously. In March 2013, three urban residents of Shanghai or Anhui, China, presented with rapidly progressing lower respiratory tract infections and were found to be infected with a novel reassortant avian-origin influenza A (H7N9) virus. METHODS We obtained and analyzed clinical, epidemiologic, and virologic data from these patients. Respiratory specimens were tested for influenza and other respiratory viruses by means of real-time reverse-transcriptase-polymerase-chain-reaction assays, viral culturing, and sequence analyses. RESULTS A novel reassortant avian-origin influenza A (H7N9) virus was isolated from respiratory specimens obtained from all three patients and was identified as H7N9. Sequencing analyses revealed that all the genes from these three viruses were of avian origin, with six internal genes from avian influenza A (H9N2) viruses. Substitution Q226L (H3 numbering) at the 210-loop in the hemagglutinin (HA) gene was found in the A/Anhui/1/2013 and A/Shanghai/2/2013 virus but not in the A/Shanghai/1/2013 virus. A T160A mutation was identified at the 150-loop in the HA gene of all three viruses. A deletion of five amino acids in the neuraminidase (NA) stalk region was found in all three viruses. All three patients presented with fever, cough, and dyspnea. Two of the patients had a history of recent exposure to poultry. Chest radiography revealed diffuse opacities and consolidation. Complications included acute respiratory distress syndrome and multiorgan failure. All three patients died. CONCLUSIONS Novel reassortant H7N9 viruses were associated with severe and fatal respiratory disease in three patients. (Funded by the National Basic Research Program of China and others.).

[1]  Bill Bynum,et al.  Lancet , 2015, The Lancet.

[2]  L. Nagarajan,et al.  Neurologic Complications of Influenza , 2014, Journal of child neurology.

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

[4]  I. Barr,et al.  Influenza Virus A (H10N7) in Chickens and Poultry Abattoir Workers, Australia , 2012, Emerging infectious diseases.

[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]  Y. Lyoo,et al.  Genetic characterization of H7N2 influenza virus isolated from pigs. , 2011, Veterinary microbiology.

[7]  T. Carpenter,et al.  Emergence and Genetic Variation of Neuraminidase Stalk Deletions in Avian Influenza Viruses , 2011, PloS one.

[8]  D. Pérez,et al.  A 27-Amino-Acid Deletion in the Neuraminidase Stalk Supports Replication of an Avian H2N2 Influenza A Virus in the Respiratory Tract of Chickens , 2010, Journal of Virology.

[9]  J. Buttery,et al.  Melting muscles: novel H1N1 influenza A associated rhabdomyolysis. , 2009, The Pediatric infectious disease journal.

[10]  K. Labadie,et al.  Host-range determinants on the PB2 protein of influenza A viruses control the interaction between the viral polymerase and nucleoprotein in human cells. , 2007, Virology.

[11]  Yi Guan,et al.  Avian Influenza Virus (H5N1): a Threat to Human Health , 2007, Clinical Microbiology Reviews.

[12]  Collective Editorial team Avian influenza A/(H7N2) outbreak in the United Kingdom. , 2007, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[13]  J. Nguyen-Van-Tam,et al.  Outbreak of low pathogenicity H7N3 avian influenza in UK, including associated case of human conjunctivitis. , 2006, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[14]  Yoshihiro Kawaoka,et al.  Influenza: lessons from past pandemics, warnings from current incidents , 2005, Nature Reviews Microbiology.

[15]  Yasuo Suzuki,et al.  Sialobiology of influenza: molecular mechanism of host range variation of influenza viruses. , 2005, Biological & pharmaceutical bulletin.

[16]  M. Peiris,et al.  Clinical features and rapid viral diagnosis of human disease associated with avian influenza A H 5 N 1 virus , 2005 .

[17]  M. Marra,et al.  Novel Avian Influenza H7N3 Strain Outbreak, British Columbia , 2004, Emerging infectious diseases.

[18]  Martin Hirst,et al.  Human Illness from Avian Influenza H7N3, British Columbia , 2004, Emerging infectious diseases.

[19]  A. Osterhaus,et al.  For Personal Use. Only Reproduce with Permission from the Lancet , 2022 .

[20]  Marion Koopmans,et al.  Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[21]  T. Kuiken,et al.  Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[22]  Y. Guan,et al.  Emergence of multiple genotypes of H5N1 avian influenza viruses in Hong Kong SAR , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[23]  S. Baigent,et al.  Glycosylation of haemagglutinin and stalk-length of neuraminidase combine to regulate the growth of avian influenza viruses in tissue culture. , 2001, Virus research.

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

[25]  Y. Kawaoka,et al.  Host-range barrier of influenza A viruses. , 2000, Veterinary microbiology.

[26]  J. Skehel,et al.  Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. , 2000, Annual review of biochemistry.

[27]  M. Peiris,et al.  Clinical features and rapid viral diagnosis of human disease associated with avian influenza A H5N1 virus , 1998, The Lancet.