Kinetic Modeling of West Nile Virus Fusion Indicates an Off-Pathway State.
ACS Infect Dis
; 6(12): 3260-3268, 2020 12 11.
Article
em En
| MEDLINE
| ID: mdl-33201665
West Nile virus (WNV) is a prominent mosquito-borne flavivirus that causes febrile illness in humans. To infect host cells, WNV virions first bind to plasma membrane receptors, then initiate membrane fusion following endocytosis. The viral transmembrane E protein, triggered by endosomal pH, catalyzes fusion while undergoing a dimer-to-trimer transition. Previously, single-particle WNV fusion data was interrogated with a stochastic cellular automaton simulation, which modeled the E proteins during the fusion process. The results supported a linear fusion mechanism, with E protein trimerization being rate-limiting. Here, we present corrections to the previous simulation, and apply them to the WNV fusion data. We observe that a linear mechanism is no longer sufficient to fit the data. Instead, an off-pathway state is necessary; these results are corroborated by per virus chemical kinetics modeling. When compared with a similar Zika virus fusion model, this suggests that off-pathway fusion mechanisms may characterize flaviviruses more broadly.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vírus do Nilo Ocidental
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Flavivirus
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Zika virus
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Infecção por Zika virus
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Culicidae
Limite:
Animals
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Humans
Idioma:
En
Revista:
ACS Infect Dis
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos