Association of IL28B variation with viral diversity and disease outcomes: relevance to hepatitis C and allergy

Hiba Alblooshi

Research output: ThesisMaster's Thesis

166 Downloads (Pure)

Abstract

[Truncated abstract] Hepatitis C is one of the most common infections worldwide affecting around 170 million individuals1. Approximately 30% of individuals that are infected with the Hepatitis C virus (HCV) will naturally resolve the infection but most develop chronic infection that often leads to liver cirrhosis and hepatocellular carcinoma1 2. Current standard of care for HCV infection involves the use of interferon alpha (pegIFN-α), an immunomodulatory molecule, and ribavirin (RBV). However, this treatment regime is only effective in about 50% of individuals. Treatment outcome is associated with HCV genotype, viral load decline during the initial phase of treatment and host genetic factors such as IL28B3-6. IL28B encodes for interferon lambda 3 and is involved in the host’s innate anti-viral response to viruses. To date, there is limited information regarding how IL28B affects viral evolution and in-turn clinical outcomes7. IFN is likely to have a role in other diseases in which the host’s innate immune response is important. In this study we examine the association between IL28B variation and HCV diversity and how this interaction may affect treatment outcome as well as the role of IL28B in allergic disease. IL28B typing and HCV sequencing was performed on three well-characterised HCV cohorts. Sixty eight samples were obtained from a cohort of chronic HCV-infected subjects in Western Australia and the Swiss HIV cohort study. These subjects were all treatment naïve at the time of sampling and had existing HCV sequence in the HCV NS5 region. DNA samples from the two cohorts were typed for the tagging SNP rs12979860 three kilobases upstream of IL28B. Ninety five samples were from a cohort of chronic genotype 1-infected subjects from Duke University, US...
Original languageEnglish
QualificationMasters
Publication statusUnpublished - 2011

Fingerprint

Virus Diseases
Hepatitis C
Hepacivirus
Hypersensitivity
Infection
Genotype
Western Australia
Ribavirin
Chronic Hepatitis C
Standard of Care
Viral Load
Innate Immunity
Interferon-alpha
Liver Cirrhosis
Interferons
Single Nucleotide Polymorphism
Cohort Studies
HIV
Viruses
DNA

Cite this

@phdthesis{3adf12ca3173448988c2812af4278794,
title = "Association of IL28B variation with viral diversity and disease outcomes: relevance to hepatitis C and allergy",
abstract = "[Truncated abstract] Hepatitis C is one of the most common infections worldwide affecting around 170 million individuals1. Approximately 30{\%} of individuals that are infected with the Hepatitis C virus (HCV) will naturally resolve the infection but most develop chronic infection that often leads to liver cirrhosis and hepatocellular carcinoma1 2. Current standard of care for HCV infection involves the use of interferon alpha (pegIFN-α), an immunomodulatory molecule, and ribavirin (RBV). However, this treatment regime is only effective in about 50{\%} of individuals. Treatment outcome is associated with HCV genotype, viral load decline during the initial phase of treatment and host genetic factors such as IL28B3-6. IL28B encodes for interferon lambda 3 and is involved in the host’s innate anti-viral response to viruses. To date, there is limited information regarding how IL28B affects viral evolution and in-turn clinical outcomes7. IFN is likely to have a role in other diseases in which the host’s innate immune response is important. In this study we examine the association between IL28B variation and HCV diversity and how this interaction may affect treatment outcome as well as the role of IL28B in allergic disease. IL28B typing and HCV sequencing was performed on three well-characterised HCV cohorts. Sixty eight samples were obtained from a cohort of chronic HCV-infected subjects in Western Australia and the Swiss HIV cohort study. These subjects were all treatment na{\"i}ve at the time of sampling and had existing HCV sequence in the HCV NS5 region. DNA samples from the two cohorts were typed for the tagging SNP rs12979860 three kilobases upstream of IL28B. Ninety five samples were from a cohort of chronic genotype 1-infected subjects from Duke University, US...",
keywords = "Hepatitis C, IL28B, Viral diversity, Allergy",
author = "Hiba Alblooshi",
year = "2011",
language = "English",

}

TY - THES

T1 - Association of IL28B variation with viral diversity and disease outcomes: relevance to hepatitis C and allergy

AU - Alblooshi, Hiba

PY - 2011

Y1 - 2011

N2 - [Truncated abstract] Hepatitis C is one of the most common infections worldwide affecting around 170 million individuals1. Approximately 30% of individuals that are infected with the Hepatitis C virus (HCV) will naturally resolve the infection but most develop chronic infection that often leads to liver cirrhosis and hepatocellular carcinoma1 2. Current standard of care for HCV infection involves the use of interferon alpha (pegIFN-α), an immunomodulatory molecule, and ribavirin (RBV). However, this treatment regime is only effective in about 50% of individuals. Treatment outcome is associated with HCV genotype, viral load decline during the initial phase of treatment and host genetic factors such as IL28B3-6. IL28B encodes for interferon lambda 3 and is involved in the host’s innate anti-viral response to viruses. To date, there is limited information regarding how IL28B affects viral evolution and in-turn clinical outcomes7. IFN is likely to have a role in other diseases in which the host’s innate immune response is important. In this study we examine the association between IL28B variation and HCV diversity and how this interaction may affect treatment outcome as well as the role of IL28B in allergic disease. IL28B typing and HCV sequencing was performed on three well-characterised HCV cohorts. Sixty eight samples were obtained from a cohort of chronic HCV-infected subjects in Western Australia and the Swiss HIV cohort study. These subjects were all treatment naïve at the time of sampling and had existing HCV sequence in the HCV NS5 region. DNA samples from the two cohorts were typed for the tagging SNP rs12979860 three kilobases upstream of IL28B. Ninety five samples were from a cohort of chronic genotype 1-infected subjects from Duke University, US...

AB - [Truncated abstract] Hepatitis C is one of the most common infections worldwide affecting around 170 million individuals1. Approximately 30% of individuals that are infected with the Hepatitis C virus (HCV) will naturally resolve the infection but most develop chronic infection that often leads to liver cirrhosis and hepatocellular carcinoma1 2. Current standard of care for HCV infection involves the use of interferon alpha (pegIFN-α), an immunomodulatory molecule, and ribavirin (RBV). However, this treatment regime is only effective in about 50% of individuals. Treatment outcome is associated with HCV genotype, viral load decline during the initial phase of treatment and host genetic factors such as IL28B3-6. IL28B encodes for interferon lambda 3 and is involved in the host’s innate anti-viral response to viruses. To date, there is limited information regarding how IL28B affects viral evolution and in-turn clinical outcomes7. IFN is likely to have a role in other diseases in which the host’s innate immune response is important. In this study we examine the association between IL28B variation and HCV diversity and how this interaction may affect treatment outcome as well as the role of IL28B in allergic disease. IL28B typing and HCV sequencing was performed on three well-characterised HCV cohorts. Sixty eight samples were obtained from a cohort of chronic HCV-infected subjects in Western Australia and the Swiss HIV cohort study. These subjects were all treatment naïve at the time of sampling and had existing HCV sequence in the HCV NS5 region. DNA samples from the two cohorts were typed for the tagging SNP rs12979860 three kilobases upstream of IL28B. Ninety five samples were from a cohort of chronic genotype 1-infected subjects from Duke University, US...

KW - Hepatitis C

KW - IL28B

KW - Viral diversity

KW - Allergy

M3 - Master's Thesis

ER -