Frequent coinfection of surface antigen-negative hepatitis B virus (silent HBV) in hepatitis C virus (HCV)-associated chronic liver disease (CLD) has been reported. The clinical and virological significance of silent HBV infection was investigated in 65 patients with HCV-associated CLD who subsequently received interferon (IFN) therapy. HBV DNA was detected in 34 (52.3%) patients by a nested polymerase chain reaction (PCR). Virologically, all of the 34 patients were found to have HBV with an eight-nucleotide deletion in the core promoter. Coinfection of silent HBV was more frequent with HCV genotype 1b than in 2a (64.3% vs. 28.6%, P<.01). With HCV genotype 1b, the serum RNA level was significantly higher (> or =10(6) copies per milliliter vs. < or =10(5) copies per milliliter) in patients with silent HBV than those without coinfection (P<.01). Clinically, silent HBV was associated with a higher level of serum alanine aminotransferase (158.5+/-104.8 vs. 121.8+/-78.6 IU/I; mean +/- SD) and a greater histological activity of hepatitis as evaluated by histological activity index score (9.4+/-3.8 vs. 8.6+/-4.5; mean +/- SD), although it was not statistically significant. Silent HBV was also associated with poor efficacy of IFN therapy (P<.01). The results suggest that silent HBV has some promoting effect for HCV replication, at least for HCV genotype 1b, and may affect the histological activity of hepatitis and IFN response in HCV-associated CLD.

Background-Several lines of evidence indicate that T-cell responses influence the progression of atherosclerotic disease.Interferon-␥ (IFN-␥)-producing T cells specific for lesional antigens, including oxidized LDLs and heat shock protein 60 (HSP60), may promote lesion development as well as plaque instability. B7-1 and B7-2 are closely related molecules expressed on antigen-presenting cells that provide costimulatory signals for T-cell activation. This study tested the hypothesis that the ability of T cells to influence atherosclerosis depends on B7-1/B7-2 costimulation. Methods and Results-B7-1/B7-2/LDL receptor (LDLR)-deficient mice and LDLR-deficient control mice were fed a 1.25% cholesterol or control diet for 8 and 20 weeks. Total serum cholesterol levels and extent and phenotype of atherosclerosis were analyzed. Splenic and lymph node CD4 ϩ T cells from the animals were cultured with mouse recombinant HSP60 or media and antigen-presenting cells and analyzed for IFN-␥ and interleukin-4 production. The absence of B7-1 and B7-2 significantly reduced early cholesterol diet-induced atherosclerotic lesion development in LDLR-deficient mice compared with B7-1/B7-2-expressing control mice. Furthermore, CD4ϩ T cells from the cholesterol-fed B7-deficient mice secreted a significantly lower amount of IFN-␥ in response to mouse HSP60 in vitro than did T cells from B7-expressing control mice. Conclusions-The data show that B7-1 and B7-2 regulated the development of atherosclerotic lesions and the priming of lesional antigen-specific T cells. This study highlights the B7-CD28 pathway as a potentially important target for immunomodulation of atherosclerosis.

The cDNA encoding rat very long-chain acyl-CoA synthetase (VLACS) was cloned, using degenerative primers synthesized according to the partial amino acid sequences of the peptide fragments of the purified rat liver enzyme. The longest cDNA insert was 2972 base pairs with a 1860-base pair open reading frame encoding 620 amino acids. The calculated molecular mass of 70,692 daltons was consistent with size of the purified enzyme. In Northern blot analysis, a single band was detected at the position of about 3 kilobases, corresponding to the size of the cloned cDNA. cDNA-directed expression in Escherichia coli resulted in accumulation of expressed protein, as an inclusion body. An antibody was raised using this expressed protein to characterize the cDNA and the enzyme. The subcellular localization of VLACS in peroxisomes and microsomes was demonstrated in Western blot analysis. The specific activity and the substrate specificity of the cDNA expressed enzyme in COS-1 cells were consistent with those of the purified rat enzyme. The predicted amino acid sequence of VLACS had a high sequence similarity to fatty acid transport protein (Schaffer, J. E., and Lodish, H. F. (1994) Cell 79, 427-436), and was considered to have domains for adenylation and thioester formation. The entire structure of VLACS was dissimilar to that of longchain acyl-CoA synthetase

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