Nagasaka A, Hige S, Kurosawa M, Yoshida J, Karino Y, Toyota J, Matsushima T, Asaka M
Third Department of Internal Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
J Med Virol. 1996 Jun;49(2):91-4. doi: 10.1002/(SICI)1096-9071(199606)49:2<91::AID-JMV4>3.0.CO;2-E.
Second-generation assays for detection of hepatitis C virus (HCV) infection that include reactivity of antibodies to core, NS3, NS4 are used because of their high sensitivity. Among these antibodies, anti-core antibody seems to be the most sensitive. However, there are some patients without anti-core antibodies, although HCV RNA is detectable by reverse transcription-polymerase chain reaction and branched DNA assay. The mechanism for the absence of anti-core antibody on its own is unclear. We therefore determined the nucleotide and deduced amino acid sequences of the core region obtained from two anti-core antibody-negative patients with HCV RNA (genotype 1b) and compared them with those of four anti-core antibody-positive patients and a previously reported sequence. Amino acids spanning 1-47, which seemed to exist in major B cell epitopes, were found to be completely conserved among these patients. Furthermore, the predictive binding motif to HLA DR4 (a.a 81-90) was completely conserved in both of the anti-core antibody-negative patients. There were various mutations in the residual amino acids spanning 49-108, but specific mutations could not be found in anti-core antibody-negative patients. These data indicate that the absence of anti-core antibody in two patients is not due to the presence of some formerly unknown viral variants, but due to a possible defect in the host's immune system.
用于检测丙型肝炎病毒（HCV）感染的第二代检测方法因其高灵敏度而被采用，这些方法包括检测针对核心蛋白、NS3、NS4的抗体反应性。在这些抗体中，抗核心抗体似乎最为敏感。然而，有一些患者虽然通过逆转录-聚合酶链反应和分支DNA检测法可检测到HCV RNA，但却没有抗核心抗体。单独出现抗核心抗体缺失的机制尚不清楚。因此，我们测定了两名HCV RNA（1b基因型）抗核心抗体阴性患者的核心区域核苷酸序列及推导的氨基酸序列，并将其与四名抗核心抗体阳性患者的序列以及先前报道的序列进行比较。发现在这些患者中，位于主要B细胞表位的第1至47位氨基酸完全保守。此外，在两名抗核心抗体阴性患者中，与HLA DR4的预测结合基序（第81至90位氨基酸）也完全保守。在第49至108位剩余氨基酸中存在各种突变，但在抗核心抗体阴性患者中未发现特定突变。这些数据表明，两名患者抗核心抗体的缺失并非由于存在某些以前未知的病毒变异体，而是可能由于宿主免疫系统存在缺陷。
