Immunological response to peptide nucleic acid and its peptide conjugate targeted to transactivation response (TAR) region of HIV-1 RNA genome.
Immunological response to peptide nucleic acid and its peptide conjugate targeted to transactivation response (TAR) region of HIV-1 RNA genome.
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针对 HIV-1 RNA 基因组反式激活反应 (TAR) 区域的肽核酸及其肽缀合物的免疫反应。
DOI：
10.1089/oli.2008.0152
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发表时间：
2008
期刊：
影响因子：
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通讯作者：
Pandey,VirendraN
中科院分区：
文献类型：
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作者：
Upadhyay,Alok;Ponzio,NicholasM;Pandey,VirendraN
抗人类免疫缺陷病毒 1 (HIV-1) 聚酰胺（肽）核酸 (PNA) 与靶向病毒基因组的细胞穿透肽 (CPP) 结合，是有效的杀病毒和抗病毒剂。早些时候，我们已经证明，抗 HIV-1 PNATAR-渗透蛋白缀合物可迅速被细胞吸收，并且当重复剂量高达 100 毫克/千克体重时，对小鼠无毒。在本研究中，我们证明裸露的 PNATAR 具有免疫惰性，这是通过用免疫抗原攻击的 PNATAR 免疫小鼠的脾细胞和淋巴结细胞的增殖反应来判断的。相比之下，PNATAR-渗透素缀合物具有中等免疫原性，主要是由于其渗透素肽成分。缀合物免疫小鼠的淋巴结细胞的细胞因子分泌谱显示促炎细胞因子水平略有升高，已知促炎细胞因子可促进 T 淋巴细胞增殖。由于候选化合物 PNATAR-petratin 缀合物对 HIV-1 显示出有效的杀病毒和抗病毒活性，因此良好的免疫反应和可忽略的毒性表明此类化合物具有强大的治疗潜力。
Anti-human immunodeficiency virus-1 (HIV-1) polyamide (peptide) nucleic acids (PNAs) conjugated with cell-penetrating peptides (CPPs) targeted to the viral genome are potent virucidal and antiviral agents. Earlier, we have shown that the anti-HIV-1 PNATAR-penetratin conjugate is rapidly taken up by cells and is nontoxic to mice when administered at repeat doses of as high as 100 mg/kg body weight. In the present studies we demonstrate that naked PNATARis immunologically inert as judged by the proliferation responses of splenocytes and lymph node cells from PNATAR-immunized mice challenged with the immunizing antigen. In contrast, PNATAR-penetratin conjugate is moderately immunogenic mainly due to its penetratin peptide component. Cytokine secretion profiles of the lymph node cells from the conjugate-immunized mice showed marginally elevated levels of proinflammatory cytokines, which are known to promote proliferation of T lymphocytes. Since the candidate compound, PNATAR-penetratin conjugate displays potent virucidal and antiviral activities against HIV-1, the favorable immunological response together with negligible toxicity suggest a strong therapeutic potential for this class of compounds.