丙型肝炎病毒准种特性的研究进展 2

HCV感染，而不是简单的病毒吸附作用〔15，22〕。这种异质性序列分布差异在用HCV感染黑猩猩时亦有报道，且某些有特别优势包括能逃避宿主免疫和在某些组织内复制的HCV株可持续存在〔25〕。Fujii等〔26〕利用PCR-SSCP法，对11例慢性丙肝患者血清及外周血单个核细胞(PBMC)中的HVR1准种株进行了比较研究后，发现有4例(36%)血清及PBMC中的HVR1准种株序列变异是一致的，2例(18%)HVR1准种株群体和序列变异均不同，另5例(45%)既未出现准种株群体改变亦末现HVR1序列变异。提示HCV感染者血清及PBMC中有不同准种株存在，而血清中HVR1准种株明显多于PBMC可能因为暴露于宿主免疫的PBMC相对不如肝组织，从而产生免疫压力差异所致。Cabot等〔22〕收集了39例HCV1b型感染的不同病情的患者的肝组织，通过对其与血清中HCV E2-NS2段核苷酸和氨基酸复杂性比较，发现95%的患者相应的氨基酸序列是一致的;有26%的患者HCV准种复杂性血清中高于肝组织，28%的患者低于肝组织，41%的患者两者相同，同样认为可能与病毒在肝细胞内复制和血浆中循环的选择性压力不同有关。早些时候Maggi等〔27〕研究比较了10例丙肝患者肝组织、PBMC及血浆中HCV E2/NS1区准种株的分布情况，结果发现所有患者肝组织及PBMC中HCV准种株有明显不同。尽管在血浆中有肯定的HCV突变株存在，但存在于肝组织和/或PBMC中的突变株并未在相应的血浆中检测到;另外，亦末发现明显的特异性嗜组织株。而最近Laskus等〔9〕研究则认为各种组织和PBMC可选择性吸附E2区不同的病毒亚群，从而影响到准种分布。

　　综上所述，尽管HCV准种株现象己经得到肯定，但为了更好地掌握HCV在体内的变异情况，其量化方法应更进一步完善和标准化。由于它决定着HCV某些重要的生物学特性，有必要建立有效的细胞和动物 HCV感染模型，进一步明确优势株与劣势株之间关系及其分布差异的重要意义。我们相信，随着对HCV变异和准种株的深入研究，必然会给临床HCV感染的有效防治带来希望。

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