Recombinant HBV PreS2 (a.a. 120-174) [His]

Recombinant strains of Saccharomyces cerevisiae, expressing the PreS2 + S envelope protein of the hepatitis B virus (HBV), were constructed using either the constitutive glyceraldehyde-3-phosphate dehydrogenase (GAP) promoter or the regulated galactose-1-phosphate uridyltransferase (GAL10) promoter. These strains were compared by determining not only the yield of PreS2 + S antigen but also the retention of the plasmid during growth and expression. When the GAP system was examined, the expression of PreS2 + S was high, but plasmid levels decreased significantly during growth. For the GAL10 system, the expression of the PreS2 + S was significantly lower, but the plasmid copy number remained high. Much higher expression levels (comparable to those obtained for GAP promoter) were achieved with the GAL10 promoter when PreS2 + S was expressed in a host strain containing a chromosomally integrated expression cassette comprised of the GAL10 promoter fused to the GAL4 positive regulatory gene, and the plasmid level remained high.

Among the 97 adult patients with acute hepatitis B who were admitted to the Toranomon Hospital in Metropolitan Tokyo during 28 years from 1976 to 2003, 31 (32%) were infected with hepatitis B virus (HBV) genotype A, nine (9%) with genotype B, 44 (45%) with genotype C, one (1%) each with genotypes E and F. HBV in the remaining 11 (11%) patients were untypeable. All the 31 patients with acute hepatitis B caused by HBV genotype A infection were male with a median age of 31 years, and 16 (52%) contracted infection through extramarital sexual contacts. The baseline HBV DNA level was higher in the seven (23%) patients in whom infection with HBV genotype A persisted than the remaining 24 (77%) with spontaneous resolution (median: > 8.7 vs. 6.0 log genome equivalents/ml, P = 0.004). Persistent infection was more frequent in patients with maximum alanine aminotransferase < 500 IU/Lthan >= 500 IU/ L (83% [5/6] vs. 4% [1/25], P = 0.0001). Of the six patients with persistent HBV genotype A infection who received interferon and/or lamivuidine for treatment of chronic active hepatitis, three (50%) responded with the loss of hepatitis B e antigen (HBeAg); hepatitis B surface antigen (HBsAg) was cleared from serum in one patient who received interferon and lamivudine in sequence. HBV genotype A persisted along with HBeAg in the remaining three patients given antiviral therapy as well as another who was not treated. In conclusion, infection with HBV genotype A prevails in patients with acute hepatitis B in Japan where genotypes B and C are common, is often contracted sexually (16/31 [52%]) and tends to persist (7/31 [23%]). Infection was cleared in only one of the six (17%) patients who received antiviral therapy. (c) 2005 Wiley-Liss, Inc.