共 105 条
Second sialic acid-binding site of influenza A virus neuraminidase: binding receptors for efficient release
被引:37
作者:
Du, Wenjuan
[1
]
de Vries, Erik
[1
]
van Kuppeveld, Frank J. M.
[1
]
Matrosovich, Mikhail
[2
]
de Haan, Cornelis A. M.
[1
]
机构:
[1] Univ Utrecht, Div Infect Dis & Immunol, Virol Sect, Dept Biomol Hlth Sci,Fac Vet Med, Yalelaan 1, NL-3584 CL Utrecht, Netherlands
[2] Philipps Univ, Inst Virol, Marburg, Germany
关键词:
hemagglutinin;
host range;
influenza A virus;
neuraminidase;
second sialic acid‐
binding site;
sialic acid;
FUNCTIONAL BALANCE;
HEMADSORPTION ACTIVITY;
SUBSTRATE-SPECIFICITY;
A(H3N2) VIRUSES;
STALK-LENGTH;
IN-VITRO;
HEMAGGLUTININ;
EVOLUTION;
OSELTAMIVIR;
TRANSMISSION;
D O I:
10.1111/febs.15668
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Influenza A viruses (IAVs) are a major cause of human respiratory tract infections and cause significant disease and mortality. Human IAVs originate from animal viruses that breached the host species barrier. IAV particles contain sialoglycan receptor-binding hemagglutinin (HA) and receptor-destroying neuraminidase (NA) in their envelope. When IAV crosses the species barrier, the functional balance between HA and NA needs to be adjusted to the sialoglycan repertoire of the novel host species. Relatively little is known about the role of NA in host adaptation in contrast to the extensively studied HA. NA prevents virion aggregation and facilitates release of (newly assembled) virions from cell surfaces and from decoy receptors abundantly present in mucus and cell glycocalyx. In addition to a highly conserved catalytic site, NA carries a second sialic acid-binding site (2SBS). The 2SBS preferentially binds alpha 2,3-linked sialic acids and enhances activity of the neighboring catalytic site by bringing/keeping multivalent substrates in close contact with this site. In this way, the 2SBS contributes to the HA-NA balance of virus particles and affects virus replication. The 2SBS is highly conserved in all NA subtypes of avian IAVs, with some notable exceptions associated with changes in the receptor-binding specificity of HA and host tropism. Conservation of the 2SBS is invariably lost in human (pandemic) viruses and in several other viruses adapted to mammalian host species. Preservation or loss of the 2SBS is likely to be an important factor of the viral host range.
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页码:5598 / 5612
页数:15
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