Kronenberger B, Sarrazin C, Hofmann W P, von Wagner M, Herrmann E, Welsch C, Elez R, Rüster B, Piiper A, Zeuzem S
Klinik für Innere Medizin II, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany.
J Viral Hepat. 2004 Jul;11(4):310-8. doi: 10.1111/j.1365-2893.2004.00508.x.
The hepatitis C virus (HCV) envelope (E)2 protein interacts with the cellular receptor CD81 leading to modulation of B and T cell function. Recently, a higher binding affinity of subtype 1a in comparison with 1b derived E2 proteins for CD81 in vitro was described. The importance of mutations within the putative CD81 binding regions of different HCV geno-/subtypes in correlation with CD81 expression is unknown. In the present study, CD81 expression on blood lymphocytes of patients with chronic hepatitis C infected with different HCV geno-/subtypes were analysed by fluorescence activated cell sorter analyses. In addition, the putative CD81 binding regions on the E2 gene comprising the hypervariable region (HVR)2 were analysed by direct sequencing. CD81 expression on CD8(+) T-lymphocytes from patients infected with subtype 1a (n = 6) was significantly higher in comparison with subtype 1b (n = 12) and 3 (n = 5) infected patients before and during antiviral therapy (P = 0.006; P = 0.021, respectively). Sequencing of the putative CD81 binding regions in the E2 protein comprising the HVR2 (codon 474-495 and 522-552 according to the HCV-1a prototype HCV-H) showed a highly conserved motif within HVR2 for subtype 1a isolates and an overall low number of mutations within the putative CD81 binding regions, whereas numerous mutations were detected for subtype 1b isolates (12.0 vs 23.6%). HCV-3 isolates showed an intermediate number of mutations within the putative binding sites (19.2%; P = 0.022). In conclusion, the highly conserved sequence within HVR2 and putative CD81 binding sites of subtype 1a isolates previously associated with a high CD81 binding affinity in vitro is correlated with high CD81 expression on CD8(+) T-lymphocytes in vivo.
丙型肝炎病毒（HCV）包膜（E）2蛋白与细胞受体CD81相互作用，从而调节B细胞和T细胞功能。最近，有人报道，与1b亚型来源的E2蛋白相比，1a亚型在体外对CD81具有更高的结合亲和力。不同HCV基因/亚型的假定CD81结合区域内的突变与CD81表达的相关性尚不清楚。在本研究中，通过荧光激活细胞分选分析，对感染不同HCV基因/亚型的慢性丙型肝炎患者血液淋巴细胞上的CD81表达进行了分析。此外，通过直接测序分析了E2基因上包含高变区（HVR）2的假定CD81结合区域。在抗病毒治疗前和治疗期间，感染1a亚型（n = 6）的患者的CD8（+）T淋巴细胞上的CD81表达，与感染1b亚型（n = 12）和3型（n = 5）的患者相比，显著更高（分别为P = 0.006；P = 0.021）。对包含HVR2的E2蛋白假定CD81结合区域进行测序（根据HCV-1a原型HCV-H的密码子474-495和522-552），结果显示，1a亚型分离株的HVR2内有一个高度保守的基序，并且假定CD81结合区域内的突变总数较少，而1b亚型分离株则检测到大量突变（12.0%对23.6%）。HCV-3分离株在假定结合位点内的突变数处于中间水平（19.2%；P = 0.022）。总之，1a亚型分离株的HVR2内高度保守的序列以及假定的CD81结合位点，此前在体外与高CD81结合亲和力相关联，在体内与CD8（+）T淋巴细胞上的高CD81表达相关。
