Clementi Nicola, Criscuolo Elena, Cappelletti Francesca, Quaranta Paola, Pistello Mauro, Diotti Roberta A, Sautto Giuseppe A, Tarr Alexander W, Mailland Federico, Concas Daniela, Burioni Roberto, Clementi Massimo, Mancini Nicasio
Microbiology and Virology Unit, 'Vita-Salute San Raffaele' University, Milan, Italy.
Microbiology and Virology Unit, 'Vita-Salute San Raffaele' University, Milan, Italy.
Antiviral Res. 2017 Jul;143:48-61. doi: 10.1016/j.antiviral.2017.03.028. Epub 2017 Apr 8.
The present study focused on inhibition of HSV-1 and -2 replication and pathogenesis in vitro and in vivo, through the selective targeting of the envelope glycoprotein D. Firstly, a human monoclonal antibody (Hu-mAb#33) was identified that could neutralise both HSV-1 and -2 at nM concentrations, including clinical isolates from patients affected by different clinical manifestations and featuring different susceptibility to acyclovir in vitro. Secondly, the potency of inhibition of both infection by cell-free viruses and cell-to-cell virus transmission was also assessed. Finally, mice receiving a single systemic injection of Hu-mAb#33 were protected from death and severe clinical manifestations following both ocular and vaginal HSV-1 and -2 lethal challenge. These results pave the way for further studies reassessing the importance of HSV entry as a novel target for therapeutic intervention and inhibition of cell-to-cell virus transmission.
本研究聚焦于通过选择性靶向包膜糖蛋白D，在体外和体内抑制单纯疱疹病毒1型（HSV-1）和2型（HSV-2）的复制及致病机制。首先，鉴定出一种人单克隆抗体（Hu-mAb#33），它能够在纳摩尔浓度下中和HSV-1和HSV-2，包括来自患有不同临床表现且对阿昔洛韦体外敏感性不同的患者的临床分离株。其次，还评估了其对无细胞病毒感染和细胞间病毒传播的抑制效力。最后，接受单次全身注射Hu-mAb#33的小鼠在眼部和阴道受到HSV-1和HSV-2致死性攻击后，可免于死亡和严重的临床表现。这些结果为进一步研究重新评估HSV进入作为治疗干预和抑制细胞间病毒传播新靶点的重要性铺平了道路。
