Effects of HA and NA glycosylation pattern changes on the transmission of avian influenza A(H7N9) virus in guinea pigs.
Avian influenza H7N9 virus has posed a concern of potential human-to-human transmission by resulting in seasonal virus-like human infection cases. To address the issue of sustained human infection with the H7N9 virus, here we investigated the effects of hemagglutinin (HA) and neuraminidase (NA) N-linked glycosylation (NLG) patterns on influenza virus transmission in a guinea pig model. Based on the NLG signatures identified in the HA and NA genetic sequences of H7N9 viruses, we generated NLG mutant viruses using either HA or NA gene of a H7N9 virus, A/Anhui/01/2013, by reverse genetics on the 2009 pandemic H1N1 virus backbone. For the H7 HA NLG mutant viruses, NLG pattern changes appeared to reduce viral transmissibility in guinea pigs. Intriguingly, however, the NLG changes in the N9 NA protein, such as a removal from residue 42 or 66 or an addition at residue 266, increased transmissibility of the mutant viruses by more than 33%, 50%, and 16%, respectively, compared with a parental N9 virus. Given the effects of HA-NA NLG changes with regard to viral transmission, we then generated the HA-NA NLG mutant viruses harboring the H7 HA of double NLG addition and the N9 NA of various NLG patterns. As seen in the HA NLG mutants above, the double NLG-added H7 HA decreased viral transmissibility. However, when the NA NLG changes occurred by a removal of residue 66 and an addition at 266 were additionally accompanied, the HA-NA NLG mutant virus recovered the transmissibility of its parental virus. These demonstrate the effects of specific HA-NA NLG changes on the H7N9 virus transmission by highlighting the importance of a HA-NA functional balance.
Department of Microbiology, The Institute for Viral Diseases, Korea University College of Medicine, Seoul 02841, Republic of Korea.
Sehee
S
Park
Department of Microbiology, The Institute for Viral Diseases, Korea University College of Medicine, Seoul 02841, Republic of Korea.
Ilseob
I
Lee
Department of Microbiology, The Institute for Viral Diseases, Korea University College of Medicine, Seoul 02841, Republic of Korea.
Jin Il
JI
Kim
Department of Microbiology, The Institute for Viral Diseases, Korea University College of Medicine, Seoul 02841, Republic of Korea.
Joon-Yong
JY
Bae
Department of Microbiology, The Institute for Viral Diseases, Korea University College of Medicine, Seoul 02841, Republic of Korea.
Kirim
K
Yoo
Department of Microbiology, The Institute for Viral Diseases, Korea University College of Medicine, Seoul 02841, Republic of Korea.
Juwon
J
Kim
Department of Microbiology, The Institute for Viral Diseases, Korea University College of Medicine, Seoul 02841, Republic of Korea.
Misun
M
Nam
Department of Microbiology, The Institute for Viral Diseases, Korea University College of Medicine, Seoul 02841, Republic of Korea.
Miso
M
Park
Department of Microbiology, The Institute for Viral Diseases, Korea University College of Medicine, Seoul 02841, Republic of Korea.
Soo-Hyeon
SH
Yun
Department of Microbiology, The Institute for Viral Diseases, Korea University College of Medicine, Seoul 02841, Republic of Korea.
Woo In
WI
Cho
Department of Microbiology, The Institute for Viral Diseases, Korea University College of Medicine, Seoul 02841, Republic of Korea.
Yeong-Su
YS
Kim
Department of Microbiology, The Institute for Viral Diseases, Korea University College of Medicine, Seoul 02841, Republic of Korea.
Yun Young
YY
Ko
Department of Microbiology, The Institute for Viral Diseases, Korea University College of Medicine, Seoul 02841, Republic of Korea. Electronic address: manseong.park@gmail.com.
Man-Seong
MS
Park
D000818:Animals; D001717:Birds; D005260:Female; D006031:Glycosylation; D006168:Guinea Pigs; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D005585:Influenza in Birds / Q000635:transmission* / Q000821:virology; D007251:Influenza, Human / Q000635:transmission / Q000821:virology; D009154:Mutation; D009439:Neuraminidase / Q000235:genetics / Q000378:metabolism*; D009976:Orthomyxoviridae Infections / Q000635:transmission* / Q000821:virology; D013997:Time Factors
D019267:Hemagglutinin Glycoproteins, Influenza Virus; C109963:hemagglutinin, avian influenza A virus; D009439:Neuraminidase
Hemagglutinin; Influenza A(H7N9) virus; N-linked glycosylation; Neuraminidase; Transmission