Open AccessHepatitis C virus and proprotein convertase subtilisin/kexin type 9: a detrimental interaction to increase viral infectivity and disrupt lipid metabolism
Author(s) -
Pirro Matteo,
Bianconi Vanessa,
Francisci Daniela,
Schiaroli Elisabetta,
Bagaglia Francesco,
Sahebkar Amirhossein,
Baldelli Franco
Publication year - 2017
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13273
Subject(s) - proprotein convertase , kexin , infectivity , biology , hepatitis c virus , virology , virus , lipoprotein , ldl receptor , endocrinology , cholesterol
From viral binding to the hepatocyte surface to extracellular virion release, the replication cycle of the hepatitis C virus ( HCV ) intersects at various levels with lipid metabolism; this leads to a derangement of the lipid profile and to increased viral infectivity. Accumulating evidence supports the crucial regulatory role of proprotein convertase subtilisin/kexin type 9 ( PCSK 9) in lipoprotein metabolism. Notably, a complex interaction between HCV and PCSK 9 has been documented. Indeed, either increased or reduced circulating PCSK 9 levels have been observed in HCV patients; this discrepancy might be related to several confounders, including HCV genotype, human immunodeficiency virus ( HIV ) coinfection and the ambiguous HCV ‐mediated influence on PCSK 9 transcription factors. On the other hand, PCSK 9 may itself influence HCV infectivity, inasmuch as the expression of different hepatocyte surface entry proteins and receptors is regulated by PCSK 9. The aim of this review is to summarize the current evidence about the complex interaction between HCV and liver lipoprotein metabolism, with a specific focus on PCSK 9. The underlying assumption of this review is that the interconnections between HCV and PCSK 9 may be central to explain viral infectivity.