目前团队已开始与美国同行合作，以便找到破坏这一机制的候选药物，未来或许能形成一个成熟的治疗方案。 作者: bigben446 时间: 2017-8-3 08:34
Nat Microbiol. 2017 Jun 19;2:17098. doi: 10.1038/nmicrobiol.2017.98.
HBV RNA pre-genome encodes specific motifs that mediate interactions with the viral core protein that promote nucleocapsid assembly.
Patel N#1, White SJ#1, Thompson RF1, Bingham R2, Weiß EU2, Maskell DP1, Zlotnick A3, Dykeman E2, Tuma R1, Twarock R2, Ranson NA1, Stockley PG1.
Author information
Abstract
Formation of the hepatitis B virus nucleocapsid is an essential step in the viral lifecycle, but its assembly is not fully understood. We report the discovery of sequence-specific interactions between the viral pre-genome and the hepatitis B core protein that play roles in defining the nucleocapsid assembly pathway. Using RNA SELEX and bioinformatics, we identified multiple regions in the pre-genomic RNA with high affinity for core protein dimers. These RNAs form stem-loops with a conserved loop motif that trigger sequence-specific assembly of virus-like particles (VLPs) at much higher fidelity and yield than in the absence of RNA. The RNA oligos do not interact with preformed RNA-free VLPs, so their effects must occur during particle assembly. Asymmetric cryo-electron microscopy reconstruction of the T = 4 VLPs assembled in the presence of one of the RNAs reveals a unique internal feature connected to the main core protein shell via lobes of density. Biophysical assays suggest that this is a complex involving several RNA oligos interacting with the C-terminal arginine-rich domains of core protein. These core protein-RNA contacts may play one or more roles in regulating the organization of the pre-genome during nucleocapsid assembly, facilitating subsequent reverse transcription and acting as a nucleation complex for nucleocapsid assembly.