磺胺脂——抗逆转录病毒治疗HIV-1感染的新候选药物。

Q4 Biochemistry, Genetics and Molecular Biology
Journal of Stem Cells Pub Date : 2012-01-01
I Birgitta Sundell, Ruth V Cortado, Prasad S Koka
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引用次数: 0

摘要

HIV-1感染患者现在可以使用新的联合药物治疗,尽管他们患有无法治愈的HIV-1感染,但可以延长他们的寿命,提高生活质量。在之前的一项研究中,我们发现硫脂能有效降低移植了人胎儿肝/胸腺组织(SCID-hu)的SCID小鼠的HIV-1病毒载量。目前的抗病毒治疗在长期使用后会增加心血管疾病和糖尿病等其他并发症的风险。需要新的有效的安全药剂。内源性硫脂是-异构体的混合物,即具有不同长链碱基和脂肪酸链长度和饱和度的硫脂分子。硫脂异构体可能具有不同的物理化学性质,即它们对不同的靶细胞具有不同的效力。其他研究人员已经证明,将硫脂掺入质膜的培养细胞孵育可以抑制HIV-1进入细胞,从而抑制细胞内HIV-1的复制。我们已经证明,硫脂对CD1d的依赖性刺激可以激活表达pDC抗原的细胞,产生I型干扰素。已知I型干扰素可以减少HIV-1的复制。这可能提供第二种可能的解释(在抑制病毒进入之后),与AZT治疗的小鼠相比,硫脂能更有效地降低HIV-1病毒载量。这篇综述的目的是显示与传统HAART治疗相比,硫脂在降低HIV-1病毒载量方面的效率。我们还讨论了HAART治疗的风险,并提出了一种替代磺胺类药物治疗HIV-1感染的临床选择。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Sulfatide--a new candidate for ART treatment in HIV-1 infection.

New combination drug treatment(s) now available to patients with HIV-1 infection allows them to live longer lives with good quality of life although they suffer from the incurable HIV-1 infection. In a previous study we found that sulfatide was efficient in lowering HIV-1 viral loads in SCID mice engrafted with human fetal liver/thymus tissues (SCID-hu). Current antiviral treatments carry an increased risk of other complications like cardiovascular disease and diabetes after long-term use. There is a need for new potent safe pharmaceutical agents. Endogenous sulfatide is a mixture of -isoforms, i.e. sulfatide molecules with different long-chain bases and fatty acid chain lengths and saturation. Sulfatide isoforms may have different physicochemical properties i.e, they are of different potency at different target cells. Other investigators have shown that incubation of cultured cells with sulfatide incorporated into the plasma membrane inhibited HIV-1 entry into the cells thereby inhibiting intracellular HIV-1 replication. We have shown that CD1d dependent stimulation by sulfatide may activate pDC antigen expressing cells that produce type I inteferons. Type I inteferons are known to reduce HIV-1 replication. This could provide a second likely explanation (after the inhibition of virus entry) for the more efficient lowering of HIV-1 viral loads in sulfatide versus AZT treated mice. This review aims to show the efficiency of sulfatide in reducing HIV-1 viral loads as compared to conventional HAART treatment. We also discuss the risks of HAART treatment and propose a clinical alternative of sulfatide in HIV-1 infection.

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来源期刊
Journal of Stem Cells
Journal of Stem Cells Medicine-Transplantation
CiteScore
0.10
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