Danova Svetla, Dobreva Lili, Mancheva Kapka, Atanasov Georgi, Simeonova Lora, Vilhelmova-Ilieva Neli
Department of General Microbiology, Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 26, Georgi Bonchev Str., 1113 Sofia, Bulgaria.
Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, 23, Georgi Bonchev Str., 1113 Sofia, Bulgaria.
Int J Mol Sci. 2024 Dec 25;26(1):74. doi: 10.3390/ijms26010074.
Herpes viruses are highly contagious agents affecting all classes of vertebrates, thus causing serious health, social, and economic losses. Within the One Health concept, novel therapeutics are extensively studied for both veterinary and human control and management of the infection, but the optimal strategy has not been invented yet. Lactic acid bacteria are key components of the microbiome that are known to play a protective role against pathogens as one of the proposed mechanisms involves compounds released from their metabolic activity. Previously, we reported the anti-herpes effect of postmetabolites isolated from Lactobacilli, and here, we confirm the inhibitory properties of another nine products against the phylogenetically distant human Herpes simplex virus-1 (HSV-1) and fish Koi Herpes virus (KHV) in cell cultures. Cytotoxicity, cytopathic effect inhibition, virucidal effect, the influence on the adsorption stage of the virus to the cells, as well as the protective effect of the postmetabolites on healthy cells were evaluated. The inhibitory effect was more pronounced against HSV-1 than against KHV at all studied viral cycle stages. Regarding the intracellular replicative steps, samples S7, S8, and S9 (Mix group) isolated from (vaginal strain) demonstrated the most distinct effect with calculated selective indices (SIs) in the range between 69.4 and 77.8 against HSV-1, and from 62.2 to 68.4 against KHV. Bioactive metabolites from various LAB species significantly inhibit extracellular HSV-1 and, to a lesser extent, KHV virions. The blockage of viral adsorption to the host cells was remarkable, as recorded by a decrease in the viral titer with Δlg ≥ 5 in the Mix group for both herpes viruses. The remaining postmetabolites also significantly inhibited viral adsorption to varying degrees with Δlg ≥ 3. Most metabolites also exerted a protective effect on healthy MDBK and CCB cells to subsequent experimental viral infection. Our results reveal new horizons for the application of LAB and their postbiotic products in the prevention and treatment of herpes diseases.
疱疹病毒是极具传染性的病原体，可感染所有脊椎动物类别，从而造成严重的健康、社会和经济损失。在“同一健康”理念下，人们广泛研究新型疗法以用于兽医领域及人类对该感染的控制和管理，但尚未找到最佳策略。乳酸菌是微生物群的关键组成部分，已知其作为一种可能的机制，通过其代谢活动释放的化合物对病原体发挥保护作用。此前，我们报道了从乳酸杆菌中分离出的代谢后产物的抗疱疹作用，在此，我们证实了另外九种产物在细胞培养中对系统发育关系较远的人类单纯疱疹病毒1型（HSV-1）和鱼类锦鲤疱疹病毒（KHV）具有抑制特性。评估了细胞毒性、细胞病变效应抑制、杀病毒作用、对病毒吸附到细胞阶段的影响以及代谢后产物对健康细胞的保护作用。在所有研究的病毒循环阶段，对HSV-1的抑制作用比对KHV更明显。关于细胞内复制步骤，从（阴道菌株）分离出的样品S7、S8和S9（混合组）表现出最显著的效果，计算得出的针对HSV-1的选择性指数（SIs）在69.4至77.8之间，针对KHV的选择性指数在62.2至68.4之间。来自各种乳酸菌物种的生物活性代谢产物显著抑制细胞外HSV-1，对KHV病毒粒子的抑制作用较小。病毒吸附到宿主细胞的过程受到显著阻断，混合组中两种疱疹病毒的病毒滴度下降Δlg≥5就记录了这一点。其余代谢后产物也不同程度地显著抑制病毒吸附，Δlg≥3。大多数代谢产物对健康的MDBK和CCB细胞在后续实验性病毒感染中也发挥了保护作用。我们的结果揭示了乳酸菌及其后生元产品在预防和治疗疱疹疾病方面应用的新前景。
