Influenza A Virus Hemagglutinin Is Produced in Different Disulfide-Bonded States.
Antioxid Redox Signal
; 35(13): 1081-1092, 2021 11 01.
Article
in English
| MEDLINE | ID: covidwho-1306508
ABSTRACT
Aims:
Influenza A virus hemagglutinin (HA) binding to sialic acid on lung epithelial cells triggers membrane fusion and infection. Host thiol isomerases have been shown to play a role in influenza A virus infection, and we hypothesized that this role involved manipulation of disulfide bonds in HA.Results:
Analysis of HA crystal structures revealed that three of the six HA disulfides occur in high-energy conformations and four of the six bonds can exist in unformed states, suggesting that the disulfide landscape of HA is generally strained and the bonds may be labile. We measured the redox state of influenza A virus HA disulfide bonds and their susceptibility to cleavage by vascular thiol isomerases. Using differential cysteine alkylation and mass spectrometry, we show that all six HA disulfide bonds exist in unformed states in â¼1 in 10 recombinant and viral surface HA molecules. Four of the six H1 and H3 HA bonds are cleaved by the vascular thiol isomerases, thioredoxin and protein disulphide isomerase, in recombinant proteins, which correlated with surface exposure of the disulfides in crystal structures. In contrast, viral surface HA disulfide bonds are impervious to five different vascular thiol isomerases. Innovation It has been assumed that the disulfide bonds in mature HA protein are intact and inert. We show that all six HA disulfide bonds can exist in unformed states.Conclusion:
These findings indicate that influenza A virus HA disulfides are naturally labile but not substrates for thiol isomerases when expressed on the viral surface.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Influenza A virus
/
Disulfides
/
Hemagglutinins
Language:
English
Journal:
Antioxid Redox Signal
Journal subject:
Metabolism
Year:
2021
Document Type:
Article
Affiliation country:
ARS.2021.0033
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