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免疫抑制对合并人类免疫缺陷病毒感染的慢性丙型肝炎患者丙型肝炎病毒准种群体组成的影响

Effect of immunosuppression on composition of quasispecies population of hepatitis C virus in patients with chronic hepatitis C coinfected with human immunodeficiency virus.

作者信息

Toyoda H, Fukuda Y, Koyama Y, Takamatsu J, Saito H, Hayakawa T

机构信息

Second Department of Internal Medicine, Nagoya University School of Medicine, Japan.

出版信息

J Hepatol. 1997 May;26(5):975-82. doi: 10.1016/s0168-8278(97)80105-5.

Abstract

BACKGROUND/AIMS: To study the effects of the immunosuppression caused by the reduction of CD4 activity on the composition of hepatitis C virus (HCV) populations, we analyzed the number of HCV quasispecies clones and the nucleotide diversity of the hypervariable region 1 (HVR1) of HCV in 37 patients with hemophilia with persistent HCV infection, with or without human immunodeficiency virus (HIV).

METHODS

The numbers of HCV quasispecies clones were measured by fluorescence single-strand conformation polymorphism analysis. Direct sequencing was used to analyze the degree of diversity of HVR1. We compared these values according to coinfection with HIV, and CD4 counts of patients.

RESULTS

There were no differences in either the number of HCV clones or the diversity between patients with and without HIV coinfection. In HIV coinfected patients the diversity decreased in association with the decrease in CD4 count while the number of HCV clones did not. The diversity of HVR1 was 3.64 +/- 5.03% in patients with a CD4 count < 50/microliters and 14.92 +/- 6.03% in patients with a CD4 count > or = 50/microliters; it was significantly lower in the former (p = 0.0002).

CONCLUSIONS

A severe reduction in the CD4 count, which is considered to cause a decline in the activity of helper T-lymphocytes, induced changes in the composition of HCV populations; one or a few quasispecies clones are predominant in the HCV population in the serum of individual patients.

摘要

背景/目的:为研究CD4活性降低所致免疫抑制对丙型肝炎病毒(HCV)群体组成的影响,我们分析了37例持续感染HCV的血友病患者(无论是否感染人类免疫缺陷病毒(HIV))中HCV准种克隆的数量以及HCV高变区1(HVR1)的核苷酸多样性。

方法

通过荧光单链构象多态性分析测定HCV准种克隆的数量。采用直接测序法分析HVR1的多样性程度。我们根据HIV合并感染情况以及患者的CD4细胞计数比较这些值。

结果

合并感染HIV与未合并感染HIV的患者之间,HCV克隆数量或多样性均无差异。在合并感染HIV的患者中,多样性随CD4细胞计数的减少而降低,而HCV克隆数量则不然。CD4细胞计数<50/微升的患者中HVR1的多样性为3.64±5.03%,CD4细胞计数≥50/微升的患者中为14.92±6.03%;前者显著更低(p = 0.0002)。

结论

CD4细胞计数严重降低(被认为会导致辅助性T淋巴细胞活性下降)会引起HCV群体组成的变化;在个体患者血清的HCV群体中,一个或少数几个准种克隆占主导地位。

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