Dataset Information

Impact of host and virus genome variability on HCV replication and response to interferon.

ABSTRACT: Since the discovery of hepatitis C virus (HCV), treatment has proven difficult and the regimen of pegylated interferon-? and ribavirin is only effective for half of patients. Evidence suggests that host and viral genome variations play a role in either viral clearance or persistence. Powerful genomic technologies have made it possible to study genome-wide associations with treatment response, which yielded critical genetic polymorphisms that predict treatment response. This has important implications for treatment of HCV infection and opened the door to the possibility of genetic marker-guided treatment (personalized medicine). This review will focus on the recent advances in understanding host and viral genetic variations with regards to treatment and the importance for future therapeutic intervention.

SUBMITTER: Schweitzer CJ

PROVIDER: S-EPMC3797205 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Impact of host and virus genome variability on HCV replication and response to interferon.

Schweitzer Cameron J CJ Liang T Jake TJ

Current opinion in virology 20130706 5

Since the discovery of hepatitis C virus (HCV), treatment has proven difficult and the regimen of pegylated interferon-α and ribavirin is only effective for half of patients. Evidence suggests that host and viral genome variations play a role in either viral clearance or persistence. Powerful genomic technologies have made it possible to study genome-wide associations with treatment response, which yielded critical genetic polymorphisms that predict treatment response. This has important implica ...[more]

PMID: 23835049

Similar Datasets

Project description:Coronaviruses (CoVs) encode multiple interferon (IFN) antagonists that modulate the host response to virus replication. Here, we evaluated the host transcriptional response to infection with murine coronaviruses encoding independent mutations in one of two different viral antagonists, the deubiquitinase (DUB) within nonstructural protein 3 or the endoribonuclease (EndoU) within nonstructural protein 15. We used transcriptomics approaches to compare the scope and kinetics of the host response to the wild-type (WT), DUBmut, and EndoUmut viruses in infected macrophages. We found that the EndoUmut virus activates a focused response that predominantly involves type I interferons and interferon-related genes, whereas the WT and DUBmut viruses more broadly stimulate upregulation of over 2,800 genes, including networks associated with activating the unfolded protein response (UPR) and the proinflammatory response associated with viral pathogenesis. This study highlights the role of viral interferon antagonists in shaping the kinetics and magnitude of the host response during virus infection and demonstrates that inactivating a dominant viral antagonist, the coronavirus endoribonuclease, dramatically alters the host response in macrophages.IMPORTANCE Macrophages are an important cell type during coronavirus infections because they "notice" the infection and respond by inducing type I interferons, which limits virus replication. In turn, coronaviruses encode proteins that mitigate the cell's ability to signal an interferon response. Here, we evaluated the host macrophage response to two independent mutant coronaviruses, one with reduced deubiquitinating activity (DUBmut) and the other containing an inactivated endoribonuclease (EndoUmut). We observed a rapid, robust, and focused response to the EndoUmut virus, which was characterized by enhanced expression of interferon and interferon-related genes. In contrast, wild-type virus and the DUBmut virus elicited a more limited interferon response and ultimately activated over 2,800 genes, including players in the unfolded protein response and proinflammatory pathways associated with progression of significant disease. This study reveals that EndoU activity substantially contributes to the ability of coronaviruses to evade the host innate response and to replicate in macrophages.

Dataset Information

Impact of host and virus genome variability on HCV replication and response to interferon.

Publications

Impact of host and virus genome variability on HCV replication and response to interferon.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets