Viral genotype correlates with distinct liver gene transcription signatures in chronic hepatitis C virus infection.
Liver Int
; 35(10): 2256-64, 2015 Oct.
Article
em En
| MEDLINE
| ID: mdl-25800823
ABSTRACT
BACKGROUND:
Chronic hepatitis C virus (HCV) infection of the liver with either genotype 1 or genotype 3 gives rise to distinct pathologies, and the two viral genotypes respond differently to antiviral therapy.METHODS:
To understand these clinical differences, we compared gene transcription profiles in liver biopsies from patients infected with either gt1 or gt3, and uninfected controls.RESULTS:
Gt1-infected biopsies displayed elevated levels of transcripts regulated by type I and type III interferons (IFN), including genes that predict response to IFN-α therapy. In contrast, genes controlled by IFN-γ were induced in gt3-infected biopsies. Moreover, IFN-γ levels were higher in gt3-infected biopsies. Analysis of hepatocyte-derived cell lines confirmed that the genes upregulated in gt3 infection were preferentially induced by IFN-γ. The transcriptional profile of gt3 infection was unaffected by IFNL4 polymorphisms, providing a rationale for the reduced predictive power of IFNL genotyping in gt3-infected patients.CONCLUSIONS:
The interactions between HCV genotypes 1 and 3 and hepatocytes are distinct. These unique interactions provide avenues to explore the biological mechanisms that drive viral genotype-specific differences in disease progression and treatment response. A greater understanding of the distinct host-pathogen interactions of the different HCV genotypes is required to facilitate optimal management of HCV infection.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Interleucinas
/
Hepatite C
/
Hepatite C Crônica
/
Fígado
Limite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Liver Int
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Reino Unido