Hepatitis C virus envelope protein dynamics and the link to hypervariable region 1
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Hepatitis C virus envelope protein dynamics and the link to hypervariable region 1. / Augestad, Elias H.; Bukh, Jens; Prentoe, Jannick.
In: Current Opinion in Virology, Vol. 50, 2021, p. 69-75.Research output: Contribution to journal › Review › Research › peer-review
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TY - JOUR
T1 - Hepatitis C virus envelope protein dynamics and the link to hypervariable region 1
AU - Augestad, Elias H.
AU - Bukh, Jens
AU - Prentoe, Jannick
N1 - Publisher Copyright: © 2021 The Author(s)
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
U2 - 10.1016/j.coviro.2021.07.006
DO - 10.1016/j.coviro.2021.07.006
M3 - Review
C2 - 34403905
AN - SCOPUS:85112419329
VL - 50
SP - 69
EP - 75
JO - Current Opinion in Virology
JF - Current Opinion in Virology
SN - 1879-6257
ER -
ID: 276651880