SUMMARYThe entire nucleotide sequence of genomic DNA was determined for hepatitis B virus (HBV) of subtype ayr, which had been derived from the blood of a Japanese asymptomatic carrier. The genome was 3215 nucleotides long, and differed in DNA sequence by 10 ~ from that of subtypes adw or ayw, but by only 2 9/0 from that of subtype adr. Amino acid sequences coded for by the S, C, P and X genes, as well as by the pre-S region, closely resembled those of subtype adr, indicating that the evolution of HBV/ayr from HBV/adr was more recent than the differentiation of the other three subtypes. In the product of the S gene, the mutually exclusive subtypic determinants of the surface antigen, d and y, were associated with variation of amino acid residues at only the 68th and 122nd positions from the N terminus, in contrast to the variation at as many as seven positions for the other set of subtypic determinants, w and r. Sequences representing high local hydrophilicity in the product of the S gene were involved in subtypic variation, although such sequences in the pre-S region were shared by HBV genomes of the various subtypes. In particular, a hydrophilic sequence of 19 amino acid residues, coded for by the pre-S(2) region and implicated in the presumed hepatotropism of HBV, was possessed in common by HBV/adr, HBV/ayr and HBV/ayw, and differed in HBV/adw by only one residue at the 9th position. This amino acid sequence appears to be a promising candidate for a synthetic peptide vaccine.

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GOR, an epitope borne by the amino acid sequence, GRRGQKAKSNPNRPL, is recognized by anti-GOR antibodies specifically found in patients with non-A, non-B hepatitis (NANBH). The epitope is not coded for by the hepatitis C virus (HCV), the presumed causative agent for NANBH, but by a single copy gene of the host. Anti-GOR antibodies, distinct from anti-HCV (c100-3) antibodies, were revealed to have dual specificities; they target both the presumed core gene product of HCV and a host component. This cross recognition is probably derived from homologous regions between the GOR epitope and a viral epitope on the core protein in HCV. It is therefore suggested that anti-GOR is an autoantibody induced by HCV infection. This may explain the autoimmune disease like aspect of NANBH pathogenesis.

ABSTRACT. Protective effects of recombinant R7 (rR7) vaccine against Leucocytozoon caulleryi in chickens were studied. After injection of oil-adjuvanted rR7 vaccine into chickens, antibody titers against second-generation schizonts (2GS) antigen of L. caulleryi (anti-2GS antibody) rapidly rose in all the immunized chickens, reached to a peak value 2 weeks after injection, and the titers persisted through 4 or 5 months after injection. Chickens having high levels of the anti-2GS antibody titers (≥ 102,400 ) at pre-challenge completely protected against sporozoites challenge of L. caulleryi. After the challenge inoculation, relatively high parasitemia of L. caulleryi was observed in all the inadequately immunized chickens having low levels of the antibody titers (≤ 3,200 ) at pre-challenge, although some of them seemed to be clinically normal. Correlation of protective effects in the immunized chickens was observed between both prevention of appearance of clinical signs and parasitemia after parasites challenge and anti-2GS antibody titers of the chickens at pre-challenge. The present study shows that chicken leucocytozoonosis can be prevented by vaccination, and humoral immunity may play an important role in the control of chicken leucocytozoonosis. KEY WORDS: humoral immunity, Leucocytozoon caulleryi, recombinant vaccine, second-generation schizont.

SUMMARYTissues of human primary hepatocellular carcinoma (PHC) from six patients infected with hepatitis B virus (HBV) were propagated in nude mice, as well as a strain of hepatitis B surface antigen-positive PHC (PLC/PRF/5). Integration of viral DNA into chromosomal DNA of tumour cells was evaluated by the capacity to hybridize with radiolabelled DNA probes, each representing fundamental parts of the HBV genome, that is S and C genes and regions pre-S and X. All PHC cells possessed region X integrated in their chromosomes. However, integration of the S gene, C gene and region pre-S was found in only six of the seven PHCs. Based on these findings, the integration of region X seems to be most closely associated with carcinogenesis in HBV infection.Epidemiological surveys (Szmuness, 1978;Beasley et al., 1981) indicate a close correlation between infection with hepatitis B virus (HBV) and the incidence of primary hepatocellular carcinoma (PHC). Moreover, DNA sequences of HBV (HBV-DNA) are integrated into genomic DNA of most patients with PHC seropositive for hepatitis B surface antigen (HBsAg), and also in an HBsAg-positive hepatoma cell line (Brechot et al