Yamamoto K, Horikita M, Tsuda F, Itoh K, Akahane Y, Yotsumoto S, Okamoto H, Miyakawa Y, Mayumi M
Immunology Division, Jichi Medical School, Tochigi-ken, Japan.
J Virol. 1994 Apr;68(4):2671-6. doi: 10.1128/JVI.68.4.2671-2676.1994.
Hepatitis B virus (HBV) DNA was extracted from sera of six carriers with hepatitis B e antigen as well as antibody to hepatitis B surface antigen and sequenced within the pre-S regions and the S gene. HBV DNA clones from five of these carriers had point mutations in the S gene, resulting in conversion from Ile-126 or Thr-126 of the wild-type virus to Ser-126 or Asn-126 in three carriers and conversion from Gly-145 to Arg-145 in three of them; clones with Asn-126 or Arg-145 were found in one carrier. All 12 clones from the other carrier had an insertion of 24 bp encoding an additional eight amino acids between Thr-123 and Cys-124. In addition, all or at least some of the HBV DNA clones from these carriers had in-phase deletions in the 5' terminus of the pre-S2 region. These results indicate that HBV escape mutants with mutations in the S gene affecting the expression of group-specific determinants would survive in some carriers after they seroconvert to antibody against surface antigen. Carriers with HBV escape mutants may transmit HBV either by donation of blood units without detectable surface antigen or through community-acquired infection, which would hardly be prevented by current hepatitis B immuneglobulin or vaccines.
从6名携带乙肝e抗原以及乙肝表面抗原抗体的携带者血清中提取乙肝病毒（HBV）DNA，并对前S区和S基因进行测序。其中5名携带者的HBV DNA克隆在S基因中存在点突变，导致3名携带者中野生型病毒的异亮氨酸-126或苏氨酸-126转换为丝氨酸-126或天冬酰胺-126，3名携带者中甘氨酸-145转换为精氨酸-145；在1名携带者中发现了天冬酰胺-126或精氨酸-145的克隆。另一名携带者的所有12个克隆在苏氨酸-123和半胱氨酸-124之间有一个24 bp的插入，编码另外8个氨基酸。此外，这些携带者的所有或至少一些HBV DNA克隆在前S2区的5'末端存在同相位缺失。这些结果表明，S基因发生突变影响群特异性决定簇表达的HBV逃逸突变体在血清转换为表面抗原抗体后会在一些携带者中存活。携带HBV逃逸突变体的携带者可能通过捐献无检测到表面抗原的血液单位或通过社区获得性感染传播HBV，而目前的乙肝免疫球蛋白或疫苗几乎无法预防这种传播。
