Surface gene mutants of hepatitis B virus in infants who develop acute or chronic infections despite immunoprophylaxis
Surface gene mutants of hepatitis B virus in infants who develop acute or chronic infections despite immunoprophylaxis
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尽管进行免疫预防但仍发生急性或慢性感染的婴儿的乙型肝炎病毒表面基因突变
DOI：
10.1002/hep.510260336
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发表时间：
1997
期刊：
影响因子：
13.5
通讯作者：
Ding‐Shinn Chen
中科院分区：
文献类型：
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作者：
H. Hsu;Mei‐Hwei Chang;Y. Ni;Hopi Lin;Sheng;Ding‐Shinn Chen
采用聚合酶链反应对4例暴发性乙型肝炎患儿、3例急性自限性乙型肝炎患儿和15例慢性乙型肝炎患儿的血清乙型肝炎病毒（HBV） DNA进行扩增，并对HBV基因组编码乙型肝炎表面抗原（HBsAg）主要抗原表位区域进行直接测序。所有婴儿都是由携带病毒的母亲所生，并从出生起就给予免疫预防。研究了13名未接受免疫预防且感染时间相当的母亲所生的携带者儿童的血清HBV DNA作为对照。一个S突变体（残基126，从Thr到Ala）最初在一个患有暴发性肝炎的婴儿中发现，4天后被另一个S突变体（残基145，从Gly到Arg）所取代。在一名患有慢性乙型肝炎的女孩中，分别在17月龄和25月龄时发现Ala - 126变异和Arg - 145变异。Arg - 145变异在一名无症状男性携带者中持续了8年，在一名慢性乙型肝炎婴儿中持续了1年。Ala - 126变异在一名早期乙型肝炎e抗原丢失的儿童中持续了11年。在大多数婴儿的母亲中，通过直接测序未在血清中检测到相应的HBsAg突变。对3名携带婴儿的10个DNA克隆进行克隆和测序后，在其母亲的血清中未发现S突变体。13例对照患者均未检测到S突变体。这些结果表明，S变异体是在宿主产生的免疫压力下出现或被选择的，或者是在乙肝免疫球蛋白和乙肝疫苗接种的作用下产生的。在一对母子中发现的S突变（残基129，Gln到Arg）提示直接母婴传播，导致免疫预防失败。感染Arg - 145变异体的儿童的家庭成员均未发生相同的变异体感染，这意味着该变异体的低传播性。
Serum hepatitis B virus (HBV) DNA from 4 infants with fulminant hepatitis B, 3 infants with acute self‐limited hepatitis B, and 15 infants with chronic HBV infection were amplified by polymerase chain reaction followed by direct sequencing of the region of HBV genome encoding the major antigenic epitopes of hepatitis B surface antigen (HBsAg). All infants were born to carrier mothers and administered immunoprophylaxis from birth. Serum HBV DNA from 13 carrier children born to carrier mothers who did not receive immunoprophylaxis and had comparable length of infection were studied as controls. An S mutant (residue 126, Thr to Ala) initially found in an infant with fulminant hepatitis was replaced by another S mutant (residue 145, Gly to Arg) 4 days later. In a girl with chronic hepatitis B, Ala‐126 variant and Arg‐145 variant were found at 17 and 25 months of age, respectively. The Arg‐145 variant persisted for 8 years in an asymptomatic male carrier and for 1 year in an infant with chronic hepatitis B. The Ala‐126 variant persisted for 11 years in one child who had an early loss of hepatitis B e antigen. In the majority of the infants' mothers, corresponding mutations in HBsAg were not detected in serum by direct sequencing. The S mutants detected in three carrier infants were not found in their mothers' serum after cloning and sequencing of 10 DNA clones from each maternal sample. None of the 13 control patients had detectable S mutants. These results suggest that S variants emerge or are selected under the immune pressure generated by the host or by administration of hepatitis B immune globulin and hepatitis B vaccination. An S mutant (residue 129, Gln to Arg) found in one mother‐infant pair suggested a direct maternal‐infant transmission, resulting in immunoprophylaxis failure. None of the family members of children infected with Arg‐145 variant had the same variant infection, implying this variant's low transmissability.