Search for hepatitis C virus negative-strand RNA sequences and analysis of viral sequences in the central nervous system: evidence of replication.
Patients with chronic hepatitis C are more likely to have significant changes in their physical and mental well-being than patients with liver disease of other etiology, and hepatitis C virus (HCV) has been occasionally implicated in diseases of the central nervous system. We analyzed the presence of the HCV negative-strand RNA sequence, which is the viral replicative intermediary, in autopsy brain tissue samples from six HCV-infected patients. Negative-strand HCV RNA was searched for by a strand-specific Tth-based reverse transcriptase PCR, and viral sequences amplified from brain tissue and serum were compared by single-strand conformational polymorphism analysis and direct sequencing. HCV RNA negative strands were detected in brain tissue in three patients. In two of these patients, serum- and brain-derived viral sequences were different and classified as belonging to different genotypes. In one of the latter patients, HCV RNA negative strands were detected in lymph node and, while being different from serum-derived sequences, were identical to those present in the brain. The results of the present study suggest that HCV can replicate in the central nervous system, probably in cells of the macrophage/monocyte lineage.
Radkowski
Marek
M
Division of Transplantation Medicine, Mayo Clinic Scottsdale, Scottsdale, Arizona 85259, USA.
Wilkinson
Jeffrey
J
Nowicki
Marek
M
Adair
Debra
D
Vargas
Hugo
H
Ingui
Craig
C
Rakela
Jorge
J
Laskus
Tomasz
T
D020121:5' Untranslated Regions / Q000235:genetics; D000328:Adult; D000368:Aged; D001344:Autopsy; D001483:Base Sequence; D001921:Brain / Q000473:pathology / Q000821:virology*; D005260:Female; D005355:Fibrosis / Q000150:complications / Q000821:virology; D015658:HIV Infections / Q000150:complications; D016174:Hepacivirus / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology*; D006526:Hepatitis C / Q000150:complications / Q000821:virology*; D006801:Humans; D008198:Lymph Nodes / Q000821:virology; D008264:Macrophages / Q000821:virology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational; D012367:RNA, Viral / Q000032:analysis* / Q000097:blood / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017361:Viral Nonstructural Proteins / Q000235:genetics; D014779:Virus Replication; D012324:RNA-Dependent RNA Polymerase
D020121:5' Untranslated Regions; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase