Chen M, Sällberg M, Sönnerborg A, Weiland O, Mattsson L, Jin L, Birkett A, Peterson D, Milich D R
Department of Molecular Biology, Scripps Research Institute, La Jolla, California 92037, USA.
Gastroenterology. 1999 Jan;116(1):135-43. doi: 10.1016/s0016-5085(99)70237-4.
BACKGROUND & AIMS: The extremely high rate of chronicity to hepatitis C virus (HVC) infection suggests an inefficient immune response. The humoral immune response to HCV was evaluated in 60 patients with chronic HCV infection and in 12 patients acutely infected with HCV.
A number of recombinant HCV antigens including the core, envelope 2 (E2), nonstructural (NS) 3, NS4, and NS5 proteins, and NS4a and E2-HVR-1 peptides were used in enzyme-linked immunoassays.
Immunoglobulin (Ig) G antibody responses to these viral antigens, except for the HCV core, were highly restricted to the IgG1 isotype. The prevalence of antibodies of the IgG1 isotype specific for the HCV core, E2, E2-HVR1, NS3 (helicase domain), NS4, and NS5 antigens was 97%, 98%, 28%, 88%, 33%, and 68%, respectively. Antibodies of the IgG3 isotype specific for E2, E2-HVR-1, NS3, NS4, and NS5 were detected in a minority of serum samples. The IgG2 and IgG4 isotypes were rarely if ever detected. Furthermore, antibody responses to HCV viral antigens were of relatively low titer and, with the exception of anti-HCV core, were delayed in appearance until the chronic phase of infection.
The IgG1 restriction, low titer, and delayed appearance of antibody responses elicited during HCV infection suggest that the immunogenicity of HCV proteins is limited in the context of natural infection. Inasmuch as recombinant HCV viral antigens perform as relatively normal immunogens in small animals, we suggest that the defective humoral immune responses during HCV infection may be attributable to an "immune avoidance" strategy.
丙型肝炎病毒（HCV）感染的极高慢性化率提示免疫反应效率低下。对60例慢性HCV感染患者和12例急性HCV感染患者的体液免疫反应进行了评估。
在酶联免疫分析中使用了多种重组HCV抗原，包括核心蛋白、包膜2（E2）蛋白、非结构（NS）3蛋白、NS4蛋白和NS5蛋白，以及NS4a和E2-HVR-1肽。
除HCV核心蛋白外，针对这些病毒抗原的免疫球蛋白（Ig）G抗体反应高度局限于IgG1亚型。针对HCV核心蛋白、E2、E2-HVR1、NS3（解旋酶结构域）、NS4和NS5抗原的IgG1亚型抗体的阳性率分别为97%、98%、28%、88%、33%和68%。在少数血清样本中检测到针对E2、E2-HVR-1、NS3、NS4和NS5的IgG3亚型抗体。很少检测到IgG2和IgG4亚型。此外，对HCV病毒抗原的抗体反应滴度相对较低，除抗HCV核心蛋白外，抗体反应出现延迟，直到感染的慢性期。
HCV感染期间引发的抗体反应的IgG1限制、低滴度和延迟出现表明，在自然感染情况下，HCV蛋白的免疫原性有限。鉴于重组HCV病毒抗原在小动物中表现为相对正常的免疫原，我们认为HCV感染期间体液免疫反应缺陷可能归因于一种“免疫逃逸”策略。
