IDENTIFICATION OF NOVEL NATURALLY OCCURRING GENETIC INTERACTIONS USING INTER-PERSON VARIATION AND VIRUS DYNAMICS IN HEPATITIS C VIRUS AND HUMAN IMMUNODEFICIENCY VIRUS INFECTIONS.
Embargo until
2021-05-01
Date
2015-08-14
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Johns Hopkins University
Abstract
Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) are two chronic viral infections of humans for which no vaccine exists. considerable research effort has focused on in vitro, ex vivo, and animal models due to inherent limitations in human research. The advent of highly quantitative and high-throughput measurement modalities from increasingly small amounts of human tissue have made it possible to generate unprecedented amounts of information from the material contained within a few drops of blood. This thesis presents three novel methods in which blood sampling of humans with HCV or HIV has generated large data sets that were then analyzed using the latest technologies and computational methods to describe previously unappreciated biological features of those infections.
This thesis explores two important aspects of HCV infection for which no surrogate for natural infection can be as informative: i) plasma microRNA signatures before, during, and after acute HCV infection using microRNA quantitative PCR array and ii) naturally occurring resistance polymorphisms in the HCV envelope to broadly neutralizing antibodies using a large panel of HCV pseudoparticles. This thesis also identifies novel restriction factors for HIV using RNA sequencing (RNAseq) technology to investigate naturally occurring inter-person variation in gene-induction in activated CD4+ T-cells of patients receiving an injection of pegylated interferon-alpha.
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Keywords
HCV, microRNA, broadly neutralizing antibody, interferon, HIV, restriction factor