Genetic Requirement for Hemagglutinin Glycosylation and Its Implications for Influenza A H1N1 Virus Evolution
| Autor: | Jin Il Kim, Ilseob Lee, Sehee Park, Min-Woong Hwang, Joon-Yong Bae, Sangmoo Lee, Jun Heo, Mee Sook Park, Adolfo García-Sastre, Man-Seong Park |
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| Rok vydání: | 2013 |
| Předmět: |
Models
Molecular Glycan Glycosylation Protein Conformation viruses Blotting Western Guinea Pigs Molecular Sequence Data Immunology Mutant Virulence Hemagglutinin (influenza) Hemagglutinin Glycoproteins Influenza Virus medicine.disease_cause Microbiology H5N1 genetic structure Madin Darby Canine Kidney Cells Evolution Molecular Mice chemistry.chemical_compound Dogs Influenza A Virus H1N1 Subtype Orthomyxoviridae Infections Neutralization Tests Virology Republic of Korea Pandemic Influenza A virus medicine Animals Humans Amino Acid Sequence Genetics Binding Sites Polymorphism Genetic Base Sequence biology Body Weight virus diseases Sequence Analysis DNA Mice Inbred C57BL HEK293 Cells Genetic Diversity and Evolution chemistry Insect Science biology.protein |
| Zdroj: | Journal of Virology. 87:7539-7549 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.00373-13 |
| Popis: | Influenza A virus has evolved and thrived in human populations. Since the 1918 influenza A pandemic, human H1N1 viruses had acquired additional N-linked glycosylation (NLG) sites within the globular head region of hemagglutinin (HA) until the NLG-free HA head pattern of the 1918 H1N1 virus was renewed with the swine-derived 2009 pandemic H1N1 virus. Moreover, the HA of the 2009 H1N1 virus appeared to be antigenically related to that of the 1918 H1N1 virus. Hence, it is possible that descendants of the 2009 H1N1 virus might recapitulate the acquisition of HA head glycosylation sites through their evolutionary drift as a means to evade preexisting immunity. We evaluate here the evolution signature of glycosylations found in the globular head region of H1 HA in order to determine their impact in the virulence and transmission of H1N1 viruses. We identified a polymorphism at HA residue 147 associated with the acquisition of glycosylation at residues 144 and 172. By in vitro and in vivo analyses using mutant viruses, we also found that the polymorphism at HA residue 147 compensated for the loss of replication, virulence, and transmissibility associated with the presence of the N-linked glycans. Our findings suggest that the polymorphism in H1 HA at position 147 modulates viral fitness by buffering the constraints caused by N-linked glycans and provide insights into the evolution dynamics of influenza viruses with implications in vaccine immunogenicity. |
| Databáze: | OpenAIRE |
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