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Journal of Virology, January 2002, p. 600-608, Vol. 76, No. 2
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.2.600-608.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Search for Hepatitis C Virus Negative-Strand RNA Sequences and Analysis of Viral Sequences in the Central Nervous System: Evidence of Replication

Marek Radkowski,1,2 Jeffrey Wilkinson,1 Marek Nowicki,3 Debra Adair,1 Hugo Vargas,1 Craig Ingui,1 Jorge Rakela,1 and Tomasz Laskus1*

Division of Transplantation Medicine, Mayo Clinic Scottsdale, Scottsdale, Arizona 85259,1 Institute of Infectious Diseases, Medical Academy, Warsaw, Poland,2 Maternal-Child Virology Research Laboratory, University of Southern California, Los Angeles, California 900333

Received 8 August 2001/ Accepted 4 October 2001

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.

* Corresponding author. Mailing address: Division of Transplantation Medicine, SC Johnson Bldg Sj3, Mayo Clinic Scottsdale, Scottsdale, AZ 85259. Phone: (480) 301-6370. Fax: (480) 301-3384. E-mail: laskus.tomasz{at}mayo.edu.

Journal of Virology, January 2002, p. 600-608, Vol. 76, No. 2
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.2.600-608.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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