title: Suboptimal Humoral Immune Response against Influenza A(H7N9) Virus Is Related to Its Internal Genes.
abstract: Influenza A(H7N9) virus pneumonia is associated with a high case fatality rate in humans. Multiple viral factors have been postulated to account for the high virulence of the virus. It has been reported that patients with influenza A(H7N9) virus infection have relatively low titers of neutralizing antibodies compared to those with seasonal influenza virus infections. In this study, we compared serum hemagglutination inhibition (HI) and microneutralization (MN) antibody titers of mice challenged with wild-type A(H7N9) viruses [H7N9(Anhui) and H7N9(Zhejiang)], an A(H1N1)pdm09 virus [pH1N1(2009)], and a recombinant A(H7N9) virus with PR8/H1N1 internal genes (rg-PR8-H7-N9). All mice infected by H7N9(Anhui) and H7N9(Zhejiang) developed serum HI antibodies at 14 days postinfection (dpi) but no detectable MN antibodies, even at 28 dpi. A low level of neutralizing activity was detected in H7N9(Anhui)- and H7N9(Zhejiang)-infected mice using fluorescent focus MN assay, but convalescent-phase serum samples obtained from H7N9(Anhui)-infected mice did not reduce the mortality of naive mice after homologous virus challenge. Reinfection with homologous A(H7N9) virus induced higher HI and MN titers than first infection. In contrast, pH1N1(2009) virus infection induced robust HI and MN antibody responses, even during the first infection. Moreover, rg-PR8-H7-N9 induced significantly higher HI and MN antibody titers than H7N9(Zhejiang). In conclusion, the internal genes of A(H7N9) virus can affect the humoral immune response against homologous viral surface proteins, which may also contribute to the virulence of A(H7N9) virus.
authors.affiliation: Department of Microbiology, The University of Hong Kong, Hong Kong, China.
authors.forename: Andrew C Y
authors.initials: AC
authors.lastname: Lee
authors.affiliation: Department of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Houshun
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Microbiology, The University of Hong Kong, Hong Kong, China State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China.
authors.forename: Anna J X
authors.initials: AJ
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, The University of Hong Kong, Hong Kong, China.
authors.forename: Can
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Microbiology, The University of Hong Kong, Hong Kong, China.
authors.forename: Pui
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Microbiology, The University of Hong Kong, Hong Kong, China.
authors.forename: Chuangen
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Microbiology, The University of Hong Kong, Hong Kong, China State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China.
authors.forename: Honglin
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Ivan F N
authors.initials: IF
authors.lastname: Hung
authors.affiliation: Department of Microbiology, The University of Hong Kong, Hong Kong, China State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China.
authors.forename: Kelvin K W
authors.initials: KK
authors.lastname: To
authors.affiliation: Department of Microbiology, The University of Hong Kong, Hong Kong, China State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China kyyuen@hku.hk.
authors.forename: Kwok-Yung
authors.initials: KY
authors.lastname: Yuen
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D056738:Cross Protection; D005814:Genes, Viral; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D056724:Immunity, Humoral; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology; D064766:Influenza A Virus, H7N9 Subtype / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D007251:Influenza, Human / Q000276:immunology / Q000821:virology; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D014763:Viral Matrix Proteins