Identification Of 22 Novel Motifs Of The Fusion Glycoprotein B Of Herpes Simplex Viruses

Cancer is currently the second leading cause of death globally and was believed to be responsible for approximately 9.6 million deaths in 2018.With an unprecedented understanding of the molecular biology,genetics and virology,oncolytic virus therapy has recently been recognized as a promising new therapeutic approach for cancer treatment.Oncolytic viruses are defined as genetically engineered or naturally occurring viruses that selectively replicate in and kill cancer cells without harming the normal tissues.In 2003,China approved the first oncolytic virus in the world.In 2015,the U.S.Food and Drug Administration(FDA)approved T-vec to treat melanoma.Herpes simplex virus(HSV)glycoprotein B(gB)is a viral surface cell entry fusion protein.Only in recent years has the importance of gB been realized in HSV infection and oncolytic HSV(oHSV)engineering.However,the detailed molecular biology of gB is still unclear,which negatively affects the construction of effective oHSVs.Objective:To observe the evolutionary relationship between the gB amino acids of our 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 gB,for constructing more effective oHSVs.Method:Here we performed a systematic comparative sequence analysis of gBs from the 9 HSV-1 and 2 HSV-2 strains,including our recently isolated new strain HSV-1-LXMW.Online software was implemented to predict gB secondary structure,motifs,and function domains.Based on an extensive literature review,a functional analysis of the predicted motifs was performed.Results:Here we reported the DNA and amino acid sequences of our recently isolated HSV-1-LXMW and found that the strain is evolutionarily close to HSV-1 strains F,H129 and SC16.22 novel motifs of HSV gB were identified for the first time.An amino acid sequence alignment of the 11 HSV strains showed that the gB motifs are conserved among HSV strains,suggesting they are functional in vivo.We further found that amino acids within 13 motifs out of the 22 motifs were reported to be functional in vivo.The gB mutants and gB engineered oHSVs were summarized.Conclusion:Our identification of the 22 novel motifs shed light on HSV gB biology and provide new insights for gB engineering to improve the efficiency and safety of oHSVs.