Hypervariable Region 1 Deletion and Required Adaptive Envelope Mutations Confer Decreased Dependency on Scavenger Receptor Class B Type I and Low-Density Lipoprotein Receptor for Hepatitis C Virus

• DOI: 10.1128/jvi.02017-13
• Publication Date: 2013-11-21T03:15:58Z
• Authors: Jannick Prentoe; Stéphanie B. N. S...; Santseharay Ramirez; Alfredo Nicosia; Judith M. Gottwein; Jens Bukh
• Keywords: Hypervariable region; Scavenger Receptor

Hypervariable region 1 (HVR1) of envelope protein 2 (E2) hepatitis C virus (HCV) serves important yet undefined roles in the viral life cycle. We previously showed that viability HVR1-deleted JFH1-based recombinants with Core-NS2 H77 (H77(ΔHVR1), genotype 1a) and S52 (S52(ΔHVR1), 3a) Huh7.5 cells was rescued by E2 substitutions N476D/S733F an E1 substitution, A369V, respectively; J6 (J6(ΔHVR1), 2a) fully viable. In single-cycle production assays, where HCV RNA transfected into entry-deficient Huh7-derived S29 low CD81 expression, we found no effect HVR1 deletion on replication or particle release for S52. pseudoparticle assays decreased entry 20- to 100-fold H77, J6, S52; restored H77(ΔHVR1), while A369V further impaired S52(ΔHVR1) entry. investigated receptor usage antibody blocking silencing cells, followed inoculation parental recombinants. Compared viruses, scavenger class B type I (SR-BI) dependency H77(ΔHVR1/N476D/S733F), H77(N476D/S733F), S52(ΔHVR1/A369V), S52(A369V), but not J6(ΔHVR1). Low-density lipoprotein (LDLr) H77(N476D/S733F) S52(A369V). Soluble LDLr neutralization revealed strong inhibition limited against viruses. Apolipoprotein E (ApoE)-specific similar viruses without HVR1. conclusion, HVR1-related adaptive mutations appeared be involved SR-BI dependency, respectively. Also, served ApoE-independent HVR1-dependent functions