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20名血友病患者中凝血因子Ⅷ和Ⅸ基因缺陷的频率与韩国红参及高效抗逆转录病毒疗法的关联:凝血因子Ⅷ和Ⅸ基因致死性突变对HIV-1进化的影响

The frequency of defective genes in and genes in 20 hemophiliacs is associated with Korean Red Ginseng and highly active antiretroviral therapy: the impact of lethal mutations in and genes on HIV-1 evolution.

作者信息

Cho Young Keol, Kim Jung-Eun

机构信息

Departments of Microbiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

出版信息

J Ginseng Res. 2021 Jan;45(1):149-155. doi: 10.1016/j.jgr.2020.03.003. Epub 2020 Apr 8.

Abstract

BACKGROUND

We have reported that internal deletions in the , , and genes in HIV-1-infected patients are induced in those treated with Korean Red Ginseng (KRG). KRG delays the development of resistance mutations to antiretroviral drugs.

METHODS

The - genes over 26 years in 20 hemophiliacs infected with HIV-1 from a single source were sequenced to investigate whether - genes were affected by KRG and KRG plus highly active antiretroviral therapy (ART) (hereafter called GCT) and compared the results with our previous data.

RESULTS

A significantly higher number of in-frame small deletions were found in the - genes of KRG-treated patients than at the baseline, in control patients, and in ART-alone patients ( < 0.001). These were significantly reduced in GCT patients ( < 0.05). In contrast, sequences harboring a premature stop codon (SC) were more significant in GCT patients (10.1%) than in KRG-alone patients, control ( < 0.01), and ART-alone patients ( = 0.078 for peripheral blood mononuclear cells). The proportion of SC in Vpr was similar to that in Vif, whereas the proportion of sequences revealing SC in the genes was significantly lower than that in the genes ( < 0.01). The genetic distance was 1.8 times higher in the sequences harboring SC than in the sequences without SC ( < 0.001). Q135P in the gene is significantly associated with rapid progression to AIDS ( < 0.01).

CONCLUSION

Our data show that KRG might induce sΔ in the v- genes and that v- genes are similarly affected by lethal mutations.

摘要

背景

我们曾报道,感染HIV-1的患者在接受高丽参(KRG)治疗后,其HIV-1的vif、vpr和vpu基因会出现内部缺失。KRG可延缓对抗逆转录病毒药物耐药性突变的产生。

方法

对来自单一来源的20名感染HIV-1的血友病患者超过26年的v-基因进行测序,以研究v-基因是否受到KRG以及KRG加高效抗逆转录病毒疗法(ART)(以下简称GCT)的影响,并将结果与我们之前的数据进行比较。

结果

在接受KRG治疗的患者的v-基因中,发现的框内小缺失数量显著高于基线水平、对照患者和单纯接受ART治疗的患者(P<0.001)。在接受GCT治疗的患者中,这些缺失显著减少(P<0.05)。相比之下,携带提前终止密码子(SC)的序列在接受GCT治疗的患者中(10.1%)比单纯接受KRG治疗的患者、对照患者(P<0.01)和单纯接受ART治疗的患者(外周血单个核细胞P=0.078)更为显著。Vpr中SC的比例与Vif中的相似,而在vpu基因中显示SC的序列比例显著低于vif基因中的比例(P<0.01)。携带SC的序列中的遗传距离比不携带SC的序列高1.8倍(P<0.001)。vpu基因中的Q135P与快速进展至艾滋病显著相关(P<0.01)。

结论

我们的数据表明,KRG可能会在v-基因中诱导sΔ,并且v-基因同样受到致死性突变的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce2c/7790868/8e7efcbc2346/gr1.jpg

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