Analysis of a point mutation in H5N1 avian influenza virus hemagglutinin in relation to virus entry into live mammalian cells.
Binding to and infection of human cells is essential for avian influenza virus transmission. Since virus binding is not always predictive for efficient infection of the cells, here we wished to investigate how hemagglutinin (HA) mutations of avian influenza virus H5N1 influence virus post-binding events in a single cycle of replication. One mutation observed in H5 HA of avian and natural human isolates from mainland China, Hong Kong, Vietnam and Thailand was identified and analyzed. The effects of the mutation on receptor binding, fusion and virus entry into cultured cells were investigated using hemadsorption, polykaryon formation and pseudotyped virus that express luciferase in the cytoplasm of transduced cell. Our results revealed that replacing aspartic acid at residue 94 with asparagine enhanced virus fusion activity and increased the binding of HA to sialic acid alpha2,6 galactose, while it decreased pseudotyped virus entry into cells expressing the avian type receptor, sialic acid alpha2,3 galactose. Our result may have implications for the understanding of the role of HA mutations in virus entry into live cells that exclusively display one type of receptor.
Su
Yan
Y
Center for Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100080, People's Republic of China.
Yang
Huai-Yi
HY
Zhang
Bao-Jiang
BJ
Jia
Hong-Ling
HL
Tien
Po
P
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D006367:HeLa Cells; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics* / Q000502:physiology; D007251:Influenza, Human / Q000821:virology*; D008969:Molecular Sequence Data; D017354:Point Mutation / Q000235:genetics*; D053586:Virus Internalization
D019267:Hemagglutinin Glycoproteins, Influenza Virus