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Hepatitis C virus envelope protein dynamics and the link to hypervariable region 1

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Conformational dynamics of viral envelope proteins seem to be involved in mediating evasion from neutralizing antibodies (NAbs) by mechanisms that limit exposure of conserved protein motifs. For hepatitis C virus (HCV), molecular studies have only recently begun to unveil how such dynamics of the envelope protein heterodimer, E1/E2, are linked to viral entry and NAb evasion. Here, we review data suggesting that E1/E2 exists in an equilibrium between theoretical ‘open’ (NAb-sensitive) and ‘closed’ (NAb-resistant) conformational states. We describe how this equilibrium is influenced by viral sequence polymorphisms and that it is critically dependent on the N-terminal region of E2, termed hypervariable region 1 (HVR1). Finally, we discuss how it appears that the virus binding site for the HCV entry co-receptor CD81 is less available in ‘closed’ E1/E2 states and that NAb-resistant viruses require a more intricate entry pathway involving also the entry co-receptor, SR-BI.

OriginalsprogEngelsk
TidsskriftCurrent Opinion in Virology
Vol/bind50
Sider (fra-til)69-75
Antal sider7
ISSN1879-6257
DOI
StatusUdgivet - 2021

Bibliografisk note

Funding Information:
This work was supported by a Novo Nordisk Foundation Distinguished lnvestigator - Bioscience and Basic Biomedicine grant (Grant number: NNF19OC0054518 ; JB), a Lundbeck Foundation Experiment grant (Grant number: R324-2019-1375 ; JP) and a Lundbeck Foundation Fellowship grant (Grant number: R335-2019-2052 ; JP).

Publisher Copyright:
© 2021 The Author(s)

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