TY - JOUR
T1 - Suboptimal Humoral Immune Response against Influenza A(H7N9) Virus Is Related to Its Internal Genes
AU - Lee, Andrew C.Y.
AU - Zhu, Houshun
AU - Zhang, Anna J.X.
AU - Li, Can
AU - Wang, Pui
AU - Li, Chuangen
AU - Chen, Honglin
AU - Hung, Ivan F.N.
AU - To, Kelvin K.W.
AU - Yuen, Kwok Yung
PY - 2015/12
Y1 - 2015/12
N2 - 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 wildtype 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 detectableMNantibodies, even at 28 dpi. A low level of neutralizing activity was detected in H7N9(Anhui)-And H7N9(Zhejiang)-infected mice using fluorescent focusMNassay, 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 andMNtiters than first infection. In contrast, pH1N1(2009) virus infection induced robust HI andMNantibody responses, even during the first infection. Moreover, rg-PR8-H7-N9 induced significantly higher HI andMNantibody 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.
AB - 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 wildtype 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 detectableMNantibodies, even at 28 dpi. A low level of neutralizing activity was detected in H7N9(Anhui)-And H7N9(Zhejiang)-infected mice using fluorescent focusMNassay, 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 andMNtiters than first infection. In contrast, pH1N1(2009) virus infection induced robust HI andMNantibody responses, even during the first infection. Moreover, rg-PR8-H7-N9 induced significantly higher HI andMNantibody 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.
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U2 - 10.1128/CVI.00443-15
DO - 10.1128/CVI.00443-15
M3 - Article
C2 - 26446420
AN - SCOPUS:84948161300
SN - 1556-6811
VL - 22
SP - 1235
EP - 1243
JO - Clinical and Vaccine Immunology
JF - Clinical and Vaccine Immunology
IS - 12
ER -