Gene Expression
Characterizing Host-Specific Responses to HCV for Targeted Clinical Discovery
A review of Host-specific response to HCV infection in the chimeric SCID-beige/Alb-uPA mouse model: Role of the innate antiviral immune response.
Note: This is a review of the published article listed below. All information, quotes, figures, methods, and findings mentioned in this review are from that article, and are the property of its authors and/or the publication in which the article originally appeared.
Kathie-Anne Walters and colleagues (2006) investigated the host-specific response to HCV infection in the chimeric SCID-beige/Alb-uPA mouse model, elucidating the role of the innate antiviral immune response. The researchers compare two mRNA samples with four replicate Agilent human 1A (V2) 22K oligonucleotide expression arrays using the dye label reverse technique. This research is is unique in that it examines the host response to a single HCV inoculum in multiple donor hepatocytes and demonstrates for the first time that host factors play a key role in this response. The findings of this study offer new insights into the mechanisms of HCV infection and potential targets for drug therapy based upon the role of host factors in the development of liver disease.
Figure 1. Expression of IFN-Inducible Genes in Human Liver Tissue from
HCV-Infected Mice
(A) Two-dimensional hierarchical clustering was done using Resolver System software with an agglomerative algorithm, complete link heuristic criteria, and Euclidean correlation metric. Each column represents gene expression data from an individual experiment (either individual HCV-infected mouse or individual liver sample). Genes were selected as at least 2-fold regulated (p < 0.05) in at least one of seven experiments. In the left panel, genes shown in red are up-regulated and genes shown in green are down-regulated in HCV-infected tissue relative to donor-matched uninfected tissue, while black indicates no change in gene expression. In the right panel, genes whose regulation showed p > 0.05 are shown in gray.
(B) RT-PCR validation of the expression array data performed for six IFN-inducible genes in a subset of HCV-infected mice. Data are shown as log10 ratio and reflect the difference in expression between donor-matched HCV-infected and naïve liver tissue.
(C) Expression of IFN-regulated genes in human and mouse liver tissue. Comparison of gene expression levels of IFN-regulated genes by RT-PCR analysis used either human- or mouse-specific probes. Data are shown as log10 ratio and reflect the difference in expression between donor-matched HCV-infected and naïve liver tissue.
Figure 2. Expression of Markers Associated with Immune Cells in HCV-Infected
Mice and Patients
Expression of genes that were at least 2-fold regulated with p = 0.05 in at least three of 13 experiments comparing uninfected mouse (blue text) and HCV-infected liver tissue (mouse samples indicated by black text, patient samples indicated with red text) to a normal liver reference.
Title: Host-Specific Response to HCV Infection in the Chimeric SCID-beige/Alb-uPA Mouse Model: Role of the Innate Antiviral Immune Response.
Journal: PLoS Pathog. 2006 Jun; 2(6): e59.
Authors: Walters KA, Joyce MA, Thompson JC, Smith MW, Yeh MM, Proll S, Zhu LF, Gao TJ, Kneteman NM, Tyrrell DL, Katze MG.
More