Genotype dependence of peptide-based Immunoassays for the detection of HCV core antibodies
Genotype dependence of peptide-based Immunoassays for the detection of HCV core antibodies
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DOI：
10.1002/jmv.21082
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发表时间：
2008-03-01
影响因子：
12.7
通讯作者：
Desai, Suresh M.
中科院分区：
文献类型：
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作者：
Muerhoff, A. Scott;Gutierrez, Robin;Desai, Suresh M.
丙型肝炎病毒(丙型肝炎病毒)抗体的检测部分受感染株的基因影响。使用1a基因衍生的重组子或多肽的免疫分析会导致感染了异源基因的个体的反应性降低。我们用基因-1a衍生的核心肽免疫分析法检测了254例感染1-4或6型丙型肝炎病毒的抗核心抗体阳性个体，以检验这种影响的大小。对应于氨基酸1-18、10-24和11-28的多肽分别与所有样本的60%、89%和85%发生反应。多肽1-18检测到78%的人感染了基因-1或2，但只有43%的人感染了基因3、4或6。还观察到肽10-24和11-28具有与基因有关的反应性。在免疫优势区域内使用34肽(包括氨基酸10-43)可在100%的样本中检测到抗体，从而消除了用较短的肽观察到的依赖于基因型的抗体检测。感染分离物的多肽和核心之间的序列差异并不能完全解释与基因型有关的反应性，因为一些人对含有相对于感染分离物的序列最多7个氨基酸差异的多肽表现出反应性，而其他具有相同核心序列的人几乎没有反应性。因此，当使用非类型特异性多肽时，丙型肝炎病毒核心序列差异只占观察到的差异核心抗体可检测性的一部分。感染相同菌株的个体之间免疫反应的差异在使用短肽检测核心抗体方面也发挥着重要作用。
Detection of hepatitis C virus (HCV) antibodies is partially influenced by the genotype of the infecting isolate. Immunoassays using genotype-1a-derived recombinants or peptides results in diminished reactivity among individuals infected with heterologous genotypes. We examined the magnitude of this effect on detection of core antibodies by using genotype-1a-derived core peptide immunoassays to test 254 HCV anti-core-positive individuals infected with genotypes 1-4 or 6. Peptides corresponding to amino acids 1-18, 10-24, and 11-28 reacted with 60%, 89%, and 85% of all samples, respectively. Peptide 1-18 detected 78% of individuals infected with genotype-1 or 2 but only 43% of those infected with genotypes 3, 4, or 6. Genotype-dependent reactivity was also observed for peptides 10-24 and 11-28. The use of a 34-mer peptide (encompassing amino acids 10-43) within the immunodominant region detected antibodies in 100% of specimens, thereby eliminating the genotype-dependent antibody detection observed with shorter peptides. Sequence differences between peptides and core of the infecting isolate did not entirely account for the genotype-dependent reactivity since some individuals displayed reactivity to peptides containing up to seven amino acid differences relative to the sequence of the infecting isolate, while others with identical core sequences had little or no reactivity. Thus, HCV core sequence divergence accounts for only a portion of the differential core antibody detectability observed when non-type-specific peptides are used. Differences in immune response between individuals infected with identical isolates also plays a significant role in core antibody detection using short peptides.