Molecular and bioinformatic evidence of hepatitis C virus evolution in brain
| Autor: | Francis J. Eng, Andrea D. Branch, Sarah L. Fishman, Susan Morgello, Jose L. Walewski, Jacinta Murray |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Untranslated region
Male Genotype Sequence analysis Hepatitis C virus Population DNA Mutational Analysis Molecular Sequence Data Viral quasispecies Hepacivirus Biology medicine.disease_cause Virus Replication Polymorphism Single Nucleotide Virus Article Cohort Studies Evolution Molecular medicine Immunology and Allergy Humans Amino Acid Sequence education Gene Phylogeny education.field_of_study virus diseases Brain Hepatitis C Chronic Virology digestive system diseases Infectious Diseases Viral replication Liver RNA Ribosomal Mutation RNA Viral Female Autopsy |
| Zdroj: | The Journal of infectious diseases. 197(4) |
| ISSN: | 0022-1899 |
| Popis: | Hepatitis C virus (HCV) causes chronic infection in ~3% of the world's population. A search for HCV in brain was prompted by complaints of fatigue and cognitive dysfunction made by patients with HCV infection [1-7]. Specific cognitive deficits and nuclear magnetic resonance abnormalities have been reported in HCV-infected patients [1, 4, 8-10]. These observations, along with increasing evidence of HCV infection and replication in peripheral blood mononuclear cells (PBMCs) [11-16], suggest that the brain may also be a compartment for extrahepatic HCV replication. To date,HCVRNAhas been amplified and sequenced from brain tissue of a limited number of subjects [17-21]. Detection of antigenomic HCV RNA has been reported in various brain regions [19]. The population of brain HCV contains sequence variants that are absent in serum. Both the presence of antigenomic HCV RNA and the presence of brain-specific variants suggest that HCV infection and replication may occur in the brain. Despite the importance of sequence analysis for investigations of brain HCV, no study has examined the suitability of postmortem (PM) material for sequence analysis, although, of necessity, such studies are almost universally performed on PM material. We developed a bioinformatic method to assess the quality of RNA templates from PM tissue. This method demonstrated that brain HCV RNA is a suitable template for sequence analysis. Sequence analysis was then conducted on portions of the 5' untranslated region (UTR) and the E1 (envelope 1) gene. Results of both direct sequencing and quasispecies analysis support the hypothesis that HCV replicates and evolves within the brain. |
| Databáze: | OpenAIRE |
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