Novel Functional Motifs of the Cell Entry Glycoprotein D for Oncolytic Herpes Simplex Viruses  

作　　者：Boxu Ren Xiaoqin Liu Yingying Wang Yanning Lyu Hongyi Xin Xiaochun Peng Ying Xiang Xianwang Wang Hongwu Xin Boxu Ren;Xiaoqin Liu;Yingying Wang;Yanning Lyu;Hongyi Xin;Xiaochun Peng;Ying Xiang;Xianwang Wang;Hongwu Xin(The Second School of Clinical Medicine, Health Science Center, Yangtze University, Jingzhou, China;Department of Nursing and Medical Imaging Technology, Yangtze University, Jingzhou, China;Laboratory of Oncology, Center for Molecular Medicine, School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, China;Department of Biochemistry and Molecular Biology, School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, China;Institute for Infectious Diseases and Endemic Diseases Prevention and Control, Beijing Center for Diseases Prevention and Control, Beijing, China;Animal Health Biotechnology, Temasek Life Sciences Laboratory, National University of Singapore, Singapore;Department of Pathophysiology, School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, China)

机构地区：[1]The Second School of Clinical Medicine, Health Science Center, Yangtze University, Jingzhou, China [2]Department of Nursing and Medical Imaging Technology, Yangtze University, Jingzhou, China [3]Laboratory of Oncology, Center for Molecular Medicine, School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, China [4]Department of Biochemistry and Molecular Biology, School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, China [5]Institute for Infectious Diseases and Endemic Diseases Prevention and Control, Beijing Center for Diseases Prevention and Control, Beijing, China [6]Animal Health Biotechnology, Temasek Life Sciences Laboratory, National University of Singapore, Singapore [7]Department of Pathophysiology, School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, China

出　　处：《Yangtze Medicine》2021年第4期266-286,共21页长江医药（英文）

摘　　要：<strong>Background:</strong> Oncolytic herpes simplex virus (oHSV) have been proved effective and safe to treat tumors. Glycoprotein D (gD) has been engineered for targeting cancer cells and de-targeting normal cells successfully, however, the effectiveness and safety of oHSVs still need to be improved. <strong>Method:</strong> Here we sequenced the DNA encoding gD of our recently isolated new strain HSV-1-LXMW and compared the gD amino acid sequence with the gDs of other 7 HSV-1 and 3 HSV-2 strains. <strong>Results:</strong> Phylogenetic analysis revealed that HSV-1-LXMW is evolutionarily close to HSV-1-Patton and -KOS strains. The gD amino acid sequence alignment identified 19 conserved and 8 variable regions. We further predicted 10 new motifs in HSV gD for the first time and identified motif differences in HSV-1 and HSV-2. We summarized the gD-engineered oHSVs and found that some of the newly identified gD motifs are actually functional. <strong>Conclusion:</strong> Our results shed light on HSV gD biology and provided new directions for future gD functional studies and engineering in order to make better oHSVs.<strong>Background:</strong> Oncolytic herpes simplex virus (oHSV) have been proved effective and safe to treat tumors. Glycoprotein D (gD) has been engineered for targeting cancer cells and de-targeting normal cells successfully, however, the effectiveness and safety of oHSVs still need to be improved. <strong>Method:</strong> Here we sequenced the DNA encoding gD of our recently isolated new strain HSV-1-LXMW and compared the gD amino acid sequence with the gDs of other 7 HSV-1 and 3 HSV-2 strains. <strong>Results:</strong> Phylogenetic analysis revealed that HSV-1-LXMW is evolutionarily close to HSV-1-Patton and -KOS strains. The gD amino acid sequence alignment identified 19 conserved and 8 variable regions. We further predicted 10 new motifs in HSV gD for the first time and identified motif differences in HSV-1 and HSV-2. We summarized the gD-engineered oHSVs and found that some of the newly identified gD motifs are actually functional. <strong>Conclusion:</strong> Our results shed light on HSV gD biology and provided new directions for future gD functional studies and engineering in order to make better oHSVs.

关 键 词：Oncolytic Herpes Simplex Virus (oHSV) Amino Acids (AA) Glycoprotein D (gD) Cancer Treatment Reengineering Virus 

分 类 号：R73[医药卫生—肿瘤]