Positive charge of Arg-201 on hemagglutinin is required for the binding of H6N1 avian influenza virus to its target through a two-step process.
Virus Res
; 265: 132-137, 2019 05.
Article
em En
| MEDLINE
| ID: mdl-30926385
ABSTRACT
In our previous study, we produced a monoclonal antibody EB2 that recognized an epitope in the HA1 domain on the hemagglutinin (HA) of H6N1 influenza virus (A/chicken/Taiwan/2838 V/00). The residue Arg-201 (R201) on this epitope was protected by the glycan at Asn-167 (N167) from tryptic digestion; therefore, the infectivity of the virus was retained. R201 was extremely conserved in various subtypes of the influenza virus. To explore the role of R201 and the protecting glycan, we developed a bi-cistronic baculovirus expression system for the production of H6HA1 and H6HA0 (nearly full-length HA), which were glycosylated in insect cells. The expressed H6HA1 was mostly found in the trimeric form, and the H6HA0 protein was only found in the monomeric form. The trimeric H6HA1 was resistant to tryptic digestion; however, it could not bind to fetuin, a glycoprotein containing sialylated N-linked and O-linked glycans. By contrast, the monomeric H6HA0 could bind to fetuin but was sensitive to tryptic digestion. We found that the positive charge on R201 was critical for binding HA to the negatively charged surface of host cells because the mutant R201A of H6HA0 lost its binding capacity substantially. Moreover, this binding capacity was dependent on the pH value and inhibited by free electrically charged amino acids. We propose a two-step model for binding the influenza virus with a host cell. The first step involved the specific recognition of the receptor binding site on HA to the sialylated glycan on the host cell. After the virus is engulfed by the acidic endosome, R201 could bind to the cell surface with stronger interactions and trigger the fusion process.
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MEDLINE
Assunto principal:
Vírus da Influenza A
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Arginina
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Glicoproteínas de Hemaglutininação de Vírus da Influenza
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Internalização do Vírus
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Interações entre Hospedeiro e Microrganismos
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article