Title:Steps and Routes of HCV Infection: The Great Promise of New Anti-Viral Targets
Volume: 16
Issue: 7
Author(s): Annalisa Crema, Antonio Ponzetto, Massimo Clementi and Guido Carloni
Affiliation:
关键词:
HCV感染,免疫机制,生命周期和靶点,传播和繁殖,阶段和通路。
摘要: A major breakthrough in understanding the steps and signalling that drives the HCV to
reach a full life-cycle has been achieved by in vitro models that have facilitated elevated virus production,
resulting in the discovery of pathways and factors involved in virus entry, translation and replication.
The HCV enters host cells through binding of its envelope glycoproteins to cell receptors, followed
by clathrin-mediated endocytosis and fusion with cell membranes, leading to virus uncoating
and cell entry. This chain of events is mediated by sequential involvement of different co-receptors, for
example, SR-B1, CD81 and the tight-junction proteins- claudin and occludin. HCV RNA replication and translation are
coupled processes, requiring cooperation of replicase, helicase and other viral proteins with cell-regulatory factors. Virion
packaging and release are highly targetable steps, although they require greater in-depth investigation. The HCV-immune
response appears to be fairly ineffective, and neutralizing antibodies that inhibit E2-CD81 binding are unable to resolve
infection. HCV-transmission through cell-to-cell contact has been implicated in the evolution of chronic infection. In particular,
CD81-dependency and the role of other co-factors involved in entry in cell-to-cell infection, as well as virus escape
from host-neutralization still require confirmation. To highlight viral and cell mechanisms implicated in HCVinfection,
we review here some of the major discoveries that have been made, from virus entry to its release from infected
cells, in understanding the HCV host-cell interplay, which may help in defining new molecular targets to provide therapeutic
antiviral strategies.