Immunology Section, Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Spanish HIV HGM BioBank, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.
Immunology Section, Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Spanish HIV HGM BioBank, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.
Eur J Pharmacol. 2017 Sep 15;811:155-163. doi: 10.1016/j.ejphar.2017.05.060. Epub 2017 May 31.
Amyloid fibrils, which are present in semen, were considered to be a cause of topical vaginal gel ineffectiveness in vivo after microbicides failed as HIV-1 prophylaxis. Therefore, it was necessary to determine whether a dendrimer was suitable for further evaluation in an in vitro model of semen-enhanced viral infection (SEVI). We demonstrated that SEVI in TZM.bl cell cultures increased the infectivity of R5-HIV-1, pTHRO.c and pCH058.c isolates, causing higher IC values for two polyanionic carbosilane dendrimers, G2-STE16 and G3-S16. However, both dendrimers maintained protection rates of 90% at non-toxic concentrations. When dendrimers were combined with Tenofovir/Maraviroc (TDF/MVC), the anti-HIV-1 effect remained at a minimum IC increase between 1- and 7-fold in the presence of amyloid fibrils. In peripheral blood mononuclear cells (PBMC), IC values were slightly influenced by the presence of semen. In brief, dendrimers combined with antiretrovirals showed a synergistic effect. This result plays a crucial role in new microbicide formulations, as it overcomes the negative effects of amyloid fibrils.
淀粉样纤维存在于精液中，曾被认为是杀微生物剂预防 HIV-1 失败后局部阴道凝胶无效的原因。因此，有必要确定树枝状大分子是否适合在精液增强病毒感染（SEVI）的体外模型中进一步评估。我们证明，在 TZM.bl 细胞培养物中的 SEVI 增加了 R5-HIV-1、pTHRO.c 和 pCH058.c 分离株的感染性，导致两种聚阴离子碳硅烷树枝状大分子 G2-STE16 和 G3-S16 的 IC 值更高。然而，两种树枝状大分子在非毒性浓度下均保持 90%的保护率。当树枝状大分子与替诺福韦/马拉韦罗（TDF/MVC）联合使用时，在存在淀粉样纤维的情况下，抗 HIV-1 作用的 IC 值仅增加 1-7 倍。在外周血单核细胞（PBMC）中，精液的存在对 IC 值的影响很小。总之，与抗逆转录病毒药物联合使用的树枝状大分子显示出协同作用。该结果在新的杀微生物剂配方中起着至关重要的作用，因为它克服了淀粉样纤维的负面影响。
