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Blood transcriptional profiling is a powerful tool for understanding global changes after infection, and may be useful for prognosis and prediction of drug treatment responses. This study characterizes the effects of chronic hepatitis C virus (HCV) infection on gene expression by analyzing blood samples from 10 treatment-naïve HCV patients and 6 healthy(More)
The type III interferons (IFN-lambda1, 2, and 3) induce an antiviral response similar to IFN-alpha/beta, but mediate their activity through a unique receptor. We found that like IFN-alpha/beta, IFN-lambda prevents the assembly of HBV capsids, demonstrating convergence of the two signaling pathways through a single antiviral mechanism. In contrast to(More)
West Nile virus (WNV) infection is usually asymptomatic but can cause severe neurological disease and death, particularly in older patients, and how individual variations in immunity contribute to disease severity is not yet defined. Animal studies identified a role for several immunity-related genes that determine the severity of infection. We have(More)
Hepatitis C virus (HCV) is the most common chronic blood-borne infection in the United States, with the majority of patients becoming chronically infected and a subset (20%) progressing to cirrhosis and hepatocellular carcinoma. Individual variations in immune responses may help define successful resistance to infection with HCV. We have compared the immune(More)
Enrichment analysis of gene sets is a popular approach that provides a functional interpretation of genome-wide expression data. Existing tests are affected by inter-gene correlations, resulting in a high Type I error. The most widely used test, Gene Set Enrichment Analysis, relies on computationally intensive permutations of sample labels to generate a(More)
Despite activating similar signaling cascades, the type I and type III interferons (IFNs) differ in their ability to antagonize virus replication. However, it is not clear whether these cytokines induce unique antiviral states, particularly in the liver, where the clinically important hepatitis B and C viruses cause persistent infection. Here, clustering(More)
BACKGROUND Genome-wide transcriptional profiling of patient blood samples offers a powerful tool to investigate underlying disease mechanisms and personalized treatment decisions. Most studies are based on analysis of total peripheral blood mononuclear cells (PBMCs), a mixed population. In this case, accuracy is inherently limited since cell subset-specific(More)
The adaptive immune system's capability to protect the body requires a highly diverse lymphocyte antigen receptor repertoire. However, the influence of individual genetic and epigenetic differences on these repertoires is not typically measured. By leveraging the unique characteristics of B, CD4(+) T and CD8(+) T-lymphocyte subsets from monozygotic twins,(More)
Low-grade, chronic inflammation has been associated with many diseases of aging, but the mechanisms responsible for producing this inflammation remain unclear. Inflammasomes can drive chronic inflammation in the context of an infectious disease or cellular stress, and they trigger the maturation of interleukin-1β (IL-1β). Here we find that the expression of(More)
Myasthenia gravis (MG) is a prototypical B cell-mediated autoimmune disease affecting 20-50 people per 100,000. The majority of patients fall into two clinically distinguishable types based on whether they produce autoantibodies targeting the acetylcholine receptor (AChR-MG) or muscle specific kinase (MuSK-MG). The autoantibodies are pathogenic, but whether(More)