Inactivation of human immunodeficiency virus type 1 by nonoxynol-9, C31G, or an alkyl sulfate, sodium dodecyl sulfate
Inactivation of human immunodeficiency virus type 1 by nonoxynol-9, C31G, or an alkyl sulfate, sodium dodecyl sulfate
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DOI：
10.1016/s0166-3542(99)00044-3
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发表时间：
1999-10-01
影响因子：
7.6
通讯作者：
Wigdahl, B
中科院分区：
文献类型：
--
作者：
Krebs, FC;Miller, SR;Wigdahl, B
预防人类免疫缺陷病毒1型(HIV-1)在性交中传播的一个非常理想的方法是开发无毒、局部、广谱的杀菌剂，有效地防止细胞相关病毒和无细胞病毒的传播。为此，评估了表面活性剂C31G和烷基硫酸盐十二烷基硫酸钠(十二烷基硫酸钠)的HIV-I灭活潜力。由于其作为杀菌剂的广泛应用，因此将其作为比较C31G和十二烷基硫酸钠的参照物。病毒灭活使用HIV-I LTR-β-半乳糖苷酶指示细胞(表达CD4或CD4/CCR5)来自人宫颈癌细胞系HeLa细胞。在检测无细胞HIV-I灭活的实验中，C31G通常比N-9更有效。用十二烷基硫酸钠灭活病毒的浓度是使用N-9或C31G灭活类似水平所需浓度的两倍。使用HeLa和HeLa来源的细胞进行细胞毒性研究，结果表明，在连续暴露48小时内，SDS的细胞毒性分别比N-9或C31G低11倍和5倍。与C31G和N-9不同，十二烷基硫酸钠可灭活无包膜病毒，例如人乳头瘤病毒(HPV)[Howett，M.K.，Neely，E.B.，Christensen，N.D.，Wigdahl，B.，Krebs，F.C.，Malamud，D.，Patrick，S.D.，Pickel，M.D.，威尔士，P.A.，Reed，C.A.，Ward，M.G.，Budjo，L.R.，Kreider，J.W.，1999。A.对性传播病毒具有杀灭病毒活性的广谱杀微生物剂。抗微生物药。化学其他探员。43(2)，314-321]。由于在C31G或N-9中添加十二烷基硫酸钠可使生成的杀微生物剂混合物对包膜和非包膜病毒广泛有效，因此对几种表面活性物质组合的灭活HIV-I的能力进行了评估。将十二烷基硫酸钠添加到C31G或N-9中，得到的混合物的效果仅略低于同等浓度的C31G或N-9。为了研究细胞相关感染性的失活，用N-9、C31G或十二烷基硫酸钠处理感染HIV-I IIIB的SupT1细胞。灭活细胞相关的传染性需要比灭活无细胞病毒所需的杀微生物剂浓度更高。然而，N-9、C31G或SDS的相对活性与无细胞病毒灭活试验中看到的相似。这些研究表明，C31G和SDS可能是有吸引力的人体试验候选药物，作为有效对抗HIV-1传播的局部杀菌剂，因为BASH的作用浓度可以提供有效的病毒灭活和低水平的细胞毒性。十二烷基硫酸钠杀微生物剂(单独使用或与其他杀微生物剂一起使用)可提供预防HPV感染的额外优势。(C)1999 Elsevier Science B.V.保留所有权利。
A highly desirable approach to prevention of human immunodeficiency virus type 1 (HIV-1) transmission during sexual intercourse is the development of nontoxic, topical, broad spectrum microbicides effective against transmission of cell-associated and cell-free virus. Toward this end, the HIV-I inactivation potential of surface active agents C31G and an alkyl sulfate, sodium dodecyl sulfate (SDS) was assessed. Because of its extensive use as a microbicidal agent, nonoxynol-9 (N-9) was used as a reference against which C31G and SDS were compared. Viral inactivation was measured using HIV-I LTR-beta-galactosidase indicator cells (expressing CD4 or CD4/CCR5) derived from HeLa cells, a cell line of human cervical adenocarcinoma origin. In experiments which examined inactivation of cell-free HIV-I, C31G was generally more effective than N-9. Viral inactivation by SDS occurred at twice the concentration necessary to achieve similar levels of inactivation using either N-9 or C31G. Using HeLa and HeLa-derived cells in cytotoxicity studies, it was demonstrated that SDS is as much as 11 and five times less cytotoxic than N-9 or C31G, respectively, during 48 h of continuous exposure. SDS (unlike C31G and N-9) can inactivate non-enveloped viruses such as human papillomavirus (HPV) [Howett, M.K., Neely, E.B., Christensen, N.D., Wigdahl, B., Krebs, F.C., Malamud, D., Patrick, S.D., Pickel, M.D., Welsh, P.A., Reed, C.A., Ward, M.G., Budgeon, L.R., Kreider, J.W., 1999. A. broad-spectrum microbicide with virucidal activity against sexually transmitted viruses. Antimicrob. Agents Chemother. 43(2), 314-321]. Since addition of SDS to C31G or N-9 may make the resulting microbicidal mixtures broadly effective against both enveloped and non-enveloped viruses, several surface active agent combinations were evaluated for their abilities to inactivate HIV-I. Addition of SDS to either C31G or N-9 resulted in mixtures that were only slightly less effective than equivalent concentrations of C31G or N-9 alone. To investigate inactivation of cell-associated infectivity, HIV-I IIIB-infected SupT1 cells were treated with N-9, C31G, or SDS. Inactivation of cell-associated infectivity required higher microbicide concentrations than were needed for inactivation of cell-free virus. However, the relative activities of N-9, C31G, or SDS were similar to those seen in assays of inactivation using cell-free virus. These studies suggest that C31G and SDS may be attractive candidates for human trials as topical microbicides effective against HIV-1 transmission since bath function at concentrations that provide effective viral inactivation with low levels of cytotoxicity. SDS microbicides (used alone or with other microbicides) may provide the added advantage of protection from HPV infection. (C) 1999 Elsevier Science B.V. All rights reserved.