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Application of shRNA-containing herpes simplex virus type 1 (HSV-1)-based gene therapy for HSV-2-induced genital herpes |
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| Authors: | Zhihong Liu Yang Xiang Zhun Wei Bo Yu Yong Shao Jie Zhang Hong Yang Manmei Li Ming Guan Jun Wan Wei Zhang |
| Affiliation: | 1. Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, No. 1120, Lianhua Road, Futian District, Shenzhen, Guangdong 518036, China;2. Biomedical Research Institute, Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, China;3. Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China;4. Shenzhen Key Laboratory for Translational Medicine of Dermatology, Shenzhen-PKU-HKUST Medical Center, No. 1120, Lianhua Road, Futian District, Shenzhen, Guangdong 518036, China;5. Shenzhen Key Discipline of Dermatology, Peking University Shenzhen Hospital, No. 1120, Lianhua Road, Futian District, Shenzhen, Guangdong 518036, China;6. Department of Dermatology, Peking University Shenzhen Hospital, No. 1120, Lianhua Road, Futian District, Shenzhen, Guangdong 518036, China;g Department of Clinical Laboratory, Peking University Shenzhen Hospital, No. 1120, Lianhua Road, Futian District, Shenzhen, Guangdong 518036, China;h JNU-HKUST Joint Laboratory, College of Pharmacy, Ji-Nan University, Guangdong, China;i Department of Laboratory Medicine, Central Laboratory, Huashan Hospital, Fudan University, Shanghai 200040, China;j Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China |
| Abstract: | HSV-1-based vectors have been widely used to achieve targeted delivery of genes into the nervous system. In the current study, we aim to use shRNA-containing HSV-1-based gene delivery system for the therapy of HSV-2 infection. Guinea pigs were infected intravaginally with HSV-2 and scored daily for 100 days for the severity of vaginal disease. HSV-2 shRNA-containing HSV-1 was applied intravaginally daily between 8 and 14 days after HSV-2 challenge. Delivery of HSV-2 shRNA-containing HSV-1 had no effect on the onset of disease and acute virus shedding in animals, but resulted in a significant reduction in both the cumulative recurrent lesion days and the number of days with recurrent disease. Around half of the animals in the HSV-2 shRNA group did not develop recurrent disease 100 days post HSV-2 infection. In conclusion, HSV-2 shRNA-containing HSV-1 particles are effective in reducing the recurrence of genital herpes caused by HSV-2. |
| Keywords: | Herpes simplex virus type 1 (HSV-1) vector Herpes simplex virus type 2 (HSV-2) Genital herpes |
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