Combinations of 3-hydroxyphthalic anhydride-modified ovalbumin with antiretroviral drug-based microbicide candidates display synergistic and complementary effects against HIV-1 infection.
Combinations of 3-hydroxyphthalic anhydride-modified ovalbumin with antiretroviral drug-based microbicide candidates display synergistic and complementary effects against HIV-1 infection.
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3-羟基邻苯二甲酸酐修饰的卵清蛋白与抗逆转录病毒药物候选杀菌剂的组合对 HIV-1 感染表现出协同和互补作用。
DOI：
10.1097/qai.0b013e31820a4a8d
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发表时间：
2011-04-15
期刊：
影响因子：
--
通讯作者：
Jiang S
中科院分区：
文献类型：
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作者：
Li L;Tan S;Lu H;Lu L;Yang J;Jin H;Liu S;Jiang S
迫切需要开发一种安全、有效且负担得起的组合杀微生物剂来预防艾滋病毒组合的性传播。我们之前的研究表明，3-羟基邻苯二甲酸酐修饰的鸡卵清蛋白 (HP-OVA) 对多种 HIV、猿猴免疫缺陷病毒 (SIV) 和单纯疱疹病毒 (HSV) 表现出有效的抗病毒活性，使其成为组合杀菌剂成分的有前景的候选者。在这里，我们打算评估 HP-OVA 与基于抗逆转录病毒药物 (ARV) 的候选杀菌剂组合的潜在协同抗 HIV-1 效果。 HP-OVA 和 ARV，包括 HIV-1 进入抑制剂（T20、C52L、NB64、NBD556、AMD3100 和 Maraviroc）和逆转录酶抑制剂（替诺福韦、UC781 和 TMC120），单独或联合测试，针对 HIV-1 X4 和 R5 病毒（包括一些耐药菌株）的抗病毒活性在 MT-2 和外周血中测定使用 p24 测定的单核细胞。采用ELISA法检测HP-OVA涂于大鼠阴道后诱导的免疫反应。当这些基于抗逆转录病毒药物的候选杀菌剂与 HP-OVA 组合时，观察到针对 X4 和 R5 菌株感染的协同活性，并且每种情况下的协同程度不同。 HP-OVA 对几种抗逆转录病毒药物 HIV-1 菌株非常有效，这表明将 HP-OVA 与这些基于抗逆转录病毒药物的候选杀菌剂组合可能会协同对抗药物敏感和耐药的 HIV-1 菌株。人体体液和人体蛋白质对 HP-OVA 介导的 HIV-1 感染抑制活性影响很小或没有影响。通用凝胶中配制的 HP-OVA 的抗病毒活性可保持至少 1 个月，并且在大鼠阴道中多次使用后仅诱导微弱的免疫反应。通过将 HP-OVA 与基于 ARV 的候选杀菌剂相结合，观察到针对广谱 HIV-1 菌株感染的协同和互补作用。这些发现为开发安全、有效且负担得起的组合杀菌剂以防止艾滋病毒和其他性传播病毒的性传播提供了良好的科学平台。
The development of a safe, effective, and affordable combination microbicide to prevent the sexual transmission of HIV combination is urgently needed. Our previous studies demonstrated that 3-hydroxyphthalic anhydride-modified chicken ovalbumin (HP-OVA) exhibited potent antiviral activity against a broad spectrum of HIV, simian immunodeficiency virus (SIV) and herpes simplex virus (HSV), making it a promising candidate as a component of combination microbicide. Here we intended to evaluate potential synergistic anti-HIV-1 effect of HP-OVA in combinations with antiretroviral drug (ARV)-based microbicide candidates. The antiviral activity of HP-OVA and the ARVs, including HIV-1 entry inhibitors (T20, C52L, NB64, NBD556, AMD3100 and Maraviroc) and reverse transcriptase inhibitors (Tenofovir, UC781 and TMC120), tested alone or in combination, against HIV-1 X4 and R5 viruses, including some drug-resistant strains, was determined in MT-2 and peripheral blood mononuclear cells using p24 assay. The immune responses induced by HP-OVA that was applied in the vaginas of rats were detected by ELISA. When each of these ARV-based microbicide candidates was combined with HP-OVA, synergistic activity was observed against infection by both X4 and R5 strains, and the degree of synergy differed in each case. HP-OVA was highly effective against several ARV-resistant HIV-1 strains, suggesting that combining HP-OVA with these ARV-based microbicide candidates might work cooperatively against both drug-sensitive and resistant HIV-1 strains. Human body fluids and human proteins had little or no effects on HP-OVA-mediated inhibitory activity against HIV-1 infection. HP-OVA formulated in the universal gel maintained its antiviral activity for at least one month and only induced weak immune responses after its multiple applications in the vaginas of rats. Synergistic and complementary effects against infection by a broad spectrum of HIV-1 strains were observed by combining HP-OVA with the ARV-based microbicide candidates. These findings provide a sound scientific platform for the development of a safe, effective and affordable combination microbicide to prevent the sexual transmission of HIV and other sexually transmissible viruses.