| Cancer has always been a serious threat to human health,and it has brought enormous economic and social burdens to humanity.Traditional cancer treatment methods include surgery,radiotherapy and chemotherapy.These treatments have obvious side effects and limitations,which cause great harm to the human body and affect the prognosis and the quality of life of cancer patients.Therefore,in the process of killing cancer cells,it is the key to minimize the damage to normal cells of the body.Tumor biotherapy has become a new treatment after traditional treatment.Oncolytic virotherapy can specifically target tumor cells and stimulate the natural immune response in the body,thereby increase the therapeutic effect of the tumor without causing damage to the normal tissues of the body,and the progeny particles released after killing the tumor cells can continue to infect surrounding tumor cells.Oncolytic herpes simplex virus(oHSV)have been proved effective and safe to treat tumors.In particular,T-VEC,which has been approved for marketing,has opened a new door for biotherapy of tumors.Specific targeting of tumor cells by modification of HSV glycoproteins proved to be safer and more effective than ?34.5 deletion of herpes simplex virus(HSV).The glycoprotein D(gD)on the surface of HSV virions is an important glycoprotein that determines the tropism of HSV,so gD can be designed to specifically target cancer cells.However,gD can stimulate the body to produce strong neutralization antibodies in vivo,these neutralizing antibodies limit the use of oHSV.Objective: To observe the evolutionary relationship between the gD amino acids of newly isolated HSV virus and the amino acid sequences of HSV viruses isolated abroad,evaluate the structural nature of these amino acid sequences,and explore the potential engineering strategy of amino acid sites of gD,thereby construct more suitable oHSV can be used in cancer treatment and imaging for Chinese.Methods: A virus was isolated from the oral cavity of an acute herpes patient in Beijing,named LXMW,and cultured.The DNA of the virus was extracted for second-generation sequencing.The gD DNA sequence was selected from the sequencing results,and translated into an amino acid sequence,and the amino acids sequence of HSV-1 strains 17,H129,RH2,SC16,Patton isolate,F,KOS and HSV-2 strains of SD90 e,HG52,G were found from the NCBI database.We obtained the amino acid sequences of these strains and predicted the functional domain and secondary structures of LXMW,HSV-1 strain 17,and HSV-2 strain HG52 gD.The phylogenetic tree of the amino acid sequence of gD of these 11 strains was constructed using MEGA7 software.The motif structure of these 11 strains was predicted using an online software(http://meme-suite.org/).Results: The gD amino acid sequence of the LXMW strain isolated in Beijing,China was similar to the HSV-1 strain Patton isolate isolated from New York,USA and the HSV-1 KOS strain isolated from Princeton,USA.The amino acid sequences of LXMW and HSV-1 Patton and KOS are identical.They have two amino acid(AA)365 and AA 369 sequences different from other HSV-1 gD sequences.AA 25 and AA 367 in HSV-1 17 are different from other HSV-1gD.AA 25 is located at the signal peptide,the other three are located in the cytoplasmic region.All HSV-1 gDs contain 394 amino acids,while HSV-2 SD90 e and HG52 has 393 amino acids and HSV-2 G has 347 amino acids.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 correlated the gD engineering sites with the newly identified motifs in gD.Conclusion:(1)gD amino acids sequence of HSV-1-LXMW is close to HSV-1-Patton and KOS isolated in American;(2)For the first time predict the motifs of gD in HSV-1 and HSV-2,the motifs have not yet been studied we predicted providing the new engineering direction for oHSV used in tumor treatment and imaging. |
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