Hepatitis C virus (HCV) is a major causative agent of posttransfusion non-A, non-B hepatitis, which often develops into malignant chronic diseases, including liver cirrhosis and hepatocellular carcinoma. We have cloned from human carriers overlapping cDNAs (9,416 bp) covering the entire coding region of the HCV genome. The latter encodes a 3,010-amino-acid polyprotein. In addition, there are 332 and 54 bases of 5' and 3' noncoding sequences, respectively. Our HCV strain has a 77% nucleic acid identity to the HCV strain cloned by workers at Chiron Corporation. The hydrophobicity profile of the putative polyprotein is similar to those of flaviviruses, but it has limited amino acid homology to polyproteins of flaviviruses and other viruses, indicating that HCV is at most distantly related to flaviviruses.
The localization of hepatitis C virus-infected hepatocytes in the human liver remains unclear despite the development of a serological assay for the antibody to hepatitis C virus. We studied their localization immunohistochemically with monoclonal antibodies to core, envelope and NS3 antigens of hepatitis C virus. We examined 48 liver biopsy samples from C100-3 antibody-positive patients with chronic liver disease (chronic persistent hepatitis, 5 cases; chronic active hepatitis, 41 cases; cirrhosis, 2 cases) and 12 liver biopsy samples from C100-3 antibody-negative patients with chronic liver disease (type B chronic hepatitis, 8 cases; alcoholic liver disease, 4 cases). In the C100-3 antibody-positive group, positive immunostaining for core antigen, envelope antigen and NS3 antigen was found in 23% (11 of 48), 24% (11 of 45) and 24% (11 of 46), respectively. Negative results were obtained in the C100-3 antibody-negative group. Hepatocytes with positive staining were scattered in the lobules, and they were found in the same regions irrespective of whether the antibody to core antigen, to envelope antigen or to NS3 antigen was used. Each positive cell was strongly stained in the cytoplasm; these decorations disappeared after absorption of the primary antibody with purified antigen. mean ALT levels in the patients with positive immunostaining for core, envelope or NS3 antigen (174.8 +/- 105.7 U/L) tended to be higher than in those with negative immunostaining (142.0 +/- 93.8 U/L). On histological evaluation of liver specimens with a scoring system of the histological activity index, intralobular inflammation and fibrosis had higher scores for samples with positive rather than negative immunostaining (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Borna disease virus (BDV) is a neurotropic, as yet unclassified, non-segmented, negative-sense, single-strand RNA virus. Natural infection with this virus has been reported to occur in horses and sheep. In addition, antibodies to BDV in plasma or BDV RNA in peripheral blood mononuclear cells (PBMCs) were also found in patients with neuropsychiatric diseases. We describe here the possible link between the patients with chronic fatigue syndrome (CFS) and infection with BDV.
Complementary DNAs to the 5' proximal region of the dengue virus type 3 RNA were cloned into bacterial plasmids and the nucleotide sequence of 3,000 bases from the 5' terminus of the genome were determined by DNA and RNA sequencing methods using dideoxy chain-termination reactions. Comparison of the nucleotide sequence thus obtained with those of other flavivirus genomes revealed significant homology existing in nucleotide sequence of the flavivirus genomes. When we compared amino acid sequence deduced from the nucleotide sequence with those of other flaviviruses, this genome region was found to include sequences encoding three viral structural proteins C, M, and E and a part of the viral nonstructural protein NS1 in this order in addition to the 5'-noncoding sequence. The characteristics and functions of these proteins were discussed based on the deduced amino acid sequences and their hydrophobic profiles. The genetic relationship of flaviviruses was also discussed based on the genetic variation observed in their genomes.
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