Gao De-Yong, Zhang Xin-Xin, Hou Gang, Jin Gen-Di, Deng Qiang, Kong Xiao-Fei, Zhang Dong-Hua, Ling Yun, Yu De-Min, Gong Qi-Ming, Zhan Qin, Yao Bi-Lian, Lu Zhi-Meng
Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, 197 Ruijin Er Road, Lu-Wan District, Shanghai 200025, China.
J Clin Microbiol. 2008 Nov;46(11):3746-51. doi: 10.1128/JCM.00612-08. Epub 2008 Oct 1.
The hepatitis C virus (HCV) alternate reading frame protein or F protein of the HCV 1b genotype is a double-frameshift product of the HCV core protein. In order to assess the presence of antibodies specific for F protein and their clinical relevance in sera from HCV patients, we produced recombinant F protein and core protein of the HCV 1b genotype in Escherichia coli. An enzyme-linked immunosorbent assay was developed using purified recombinant HCV core, F protein, and a 99-residue synthetic F peptide (F99). The seroprevalences of anticore, anti-F protein, and anti-F99 synthetic peptide were 95%, 68%, and 36%, respectively, in 168 HCV patients. The prevalence of anti-F antibodies did not correlate with viral load, genotype, or alanine aminotransferase level. Interferon combination therapy induced a decline in the level of anti-F antibodies in 55 responders (P < 0.01). Thirteen responders (24%) lost their anti-F recombinant protein antibodies, and 17 (31%) lost their anti-F synthetic peptide antibodies, whereas no decrease was observed for the 17 nonresponders. These changes were significant between responders and nonresponders (P < 0.05). Meanwhile, no change was found in the anticore antibody titer of the 72 treated patients. The percentage of anti-F-protein-negative patients (15/15 [100%]) who achieved a sustained virological response (SVR) was higher than that of the anti-F-positive patients (70%) (P < 0.05). Based on these findings, HCV F protein elicits a specific antibody response other than the anticore protein response. Our data also suggest that the presence and level of anti-F antibody responses might be influenced by the treatment (interferon plus ribavirin) and associated with an SVR in Chinese hepatitis C patients.
丙型肝炎病毒(HCV)1b基因型的交替阅读框蛋白或F蛋白是HCV核心蛋白的双移码产物。为了评估HCV患者血清中F蛋白特异性抗体的存在情况及其临床相关性,我们在大肠杆菌中制备了HCV 1b基因型的重组F蛋白和核心蛋白。利用纯化的重组HCV核心蛋白、F蛋白和一种99个氨基酸残基的合成F肽(F99)建立了酶联免疫吸附试验。在168例HCV患者中,抗核心抗体、抗F蛋白抗体和抗F99合成肽的血清阳性率分别为95%、68%和36%。抗F抗体的阳性率与病毒载量、基因型或丙氨酸转氨酶水平无关。干扰素联合治疗使55例有反应者的抗F抗体水平下降(P<0.01)。13例有反应者(24%)失去了抗F重组蛋白抗体,17例(31%)失去了抗F合成肽抗体,而17例无反应者未观察到抗体水平下降。有反应者和无反应者之间的这些变化具有显著性差异(P<0.05)。同时,72例接受治疗患者的抗核心抗体滴度未发现变化。实现持续病毒学应答(SVR)的抗F蛋白阴性患者比例(15/15[100%])高于抗F蛋白阳性患者(70%)(P<0.05)。基于这些发现,HCV F蛋白除了引发抗核心蛋白反应外,还引发特异性抗体反应。我们的数据还表明,抗F抗体反应的存在和水平可能受治疗(干扰素加利巴韦林)影响,并且与中国丙型肝炎患者的SVR相关。