1. Occult Hepatitis C Virus Infection: Are We Digging Too Deep?
George Koutsoudakis, Sofía Pérez-del-Pulgar, Xavier Forns 
Gastroenterology 
Volume 152, Issue 3, Pages (February 2017)
DOI: /j.gastro
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2. Figure 1
Model of chronic versus occult HCV infection. During chronic infection (left), HCV virions circulate in the blood stream in association with lipoproteins (LVPs). After entry (step 1) and uncoating, HCV RNA is translated in the rough endoplasmic reticulum to give rise to the viral polyprotein, which is then cleaved into mature proteins (step 2). Viral proteins in collaboration with host factors promote the formation of intracellular membrane alterations which constitute the membranous web (step 3). DMVs are the main constituents of the membranous web in which HCV RNA replication takes place. The (+) RNA serves as a template for the generation of a negative-sense copy of the genome [(-) RNA] and likely these molecules form a dsRNA. DMVs may protect dsRNA from recognition by dsRNA sensors (TLR3, MDA5, and RIG-I). dsRNA then serves as a template for the production of progeny positive- and negative-sense copies of the genome (step 4). Excess of positive-strand genomes guaranties exit of these molecules to the encapsidation sites (lipid droplets) where assembly of new virions likely takes place (step 5). Finally, the newly synthesized virions are associated with lipoproteins and are released by the constitutive secretory pathway (step 6), and are capable of infecting other hepatocytes and potentially PBMCs. During occult infection (right), ineffective IFN-mediated responses could explain, in part, low-level HCV RNA persistence. Alternatively, HCV RNA may remain protected inside the DMVs of hepatocytes or in a yet unknown cell compartment, or inside PMBCs; the deficiency in particle production may be explained by an altered ratio of (+) versus (-) strand HCV RNA. (-) RNA, negative-strand RNA; (+) RNA, positive-strand RNA; CLDN1, claudin 1; DMVs, double membrane vesicles; dsRNA, double-stranded RNA; HCV, hepatitis C virus; LD, lipid droplets; LVPs, lipoviral particles; MDA5, melanoma differentiation-associated gene 5; OCLN, occludin; PBMCs, peripheral blood mononuclear cells; RIG-I, retinoic acid-inducible gene-I; SR-B1, scavenger receptor class B type 1; TLR3, Toll-like receptor 3.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2017 AGA Institute Terms and Conditions