Changes in the hemagglutinin molecule of influenza type A (H3N2) virus associated with increased virulence for mice
Autor: | E M Anders, Patrick C. Reading, Alister C. Ward, Carol A. Hartley |
---|---|
Rok vydání: | 1997 |
Předmět: |
Male
Molecular Sequence Data Orthomyxoviridae Mutant Hemagglutinin (influenza) Virulence Collectin Hemagglutinin Glycoproteins Influenza Virus medicine.disease_cause Virus Microbiology Mice Virology Influenza A virus medicine Animals chemistry.chemical_classification biology Influenza A Virus H3N2 Subtype General Medicine biology.organism_classification Mice Inbred C57BL chemistry Mutation biology.protein Cattle Female Glycoprotein |
Zdroj: | Archives of Virology. 142:75-88 |
ISSN: | 1432-8798 0304-8608 |
DOI: | 10.1007/s007050050060 |
Popis: | The H3N2 influenza virus A/Philippines/82 (Phil82) and its bovine serum-resistant mutant, Phil82/BS, were used to investigate factors that influence virulence of influenza virus for mice. Phil82/BS, which lacks the high-mannose oligosaccharide at residue 165 of the hemagglutinin (HA) molecule, was found to replicate to a much higher titer in mouse lung than the parent Phil82, and had acquired lethality for mice. Further adaptation of Phil82/BS by sequential lung passage in mice yielded a strain of greater virulence, Phil82/BS/ML 10, in which a change at residue 246 of HA resulted in loss of a second potential glycosylation site. Phil82 is highly sensitive to neutralization in vitro by murine serum- and lung-associated mannose-binding lectins (collectins). Characterization of the two mutant viruses indicated that resistance to murine collectins can account for the enhanced virulence of Phil82/BS but not for the further increase in virulence of Phil82/BS/ML10. Evidence is presented that residue 246 is not in fact glycosylated in Phil82/BS HA, nor presumably in the parent Phil82 virus. The HA molecule of Phil82/BS/ML10 displayed functional differences from Phil82/BS, including a change in the optimum pH of fusion and a minor change in receptor-binding specificity, which may allow improved efficiency of replication in the mouse lung. |
Databáze: | OpenAIRE |
Externí odkaz: |