Identification of 22 Novel Motifs of the Cell Entry Fusion Glycoprotein B of Oncolytic Herpes Simplex Viruses: Sequence Analysis and Literature Review

Objective: Herpes simplex viruses (HSVs) are widely spread throughout the world, causing infections from oral, and genital mucous membrane ulcerations to severe viral encephalitis. Glycoprotein B (gB) was the first HSV envelope glycoprotein identified to induce cell fusion. This glycoprotein initiates viral entry and thereby determines the infectivity of HSV, as well as oncolytic HSV (oHSV). Clarifying its molecular characterization and enlarging its motif reservoir will help to engineer oHSV and in cancer treatment applications. Only in recent years has the importance of gB been acknowledged in HSV infection and oHSV engineering. Although gB-modified oHSVs have been developed, the detailed molecular biology of gB needs to be illustrated more clearly in order to construct 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 HSV-1-LXMW, which was isolated by our lab. Online software was implemented to predict gB secondary structure and motifs. Based on extensive literature reviews, a functional analysis of the predicted motifs was performed. Results: Here, we reported the DNA and predicted amino acid sequences of our recently isolated HSV-1-LXMW and found that the strain was evolutionarily close to HSV-1 strains F, H129, and SC16 based on gB analysis. The 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 that they are functional in vivo. Additionally, we found that certain amino acids within the 13 motifs out of the 22 were reported to be functional in vivo. Furthermore, the gB mutants and gB-engineered oHSVs were also summarized. Conclusion: Our identification of the 22 novel motifs shed light on HSV gB biology and provide new options for gB engineering to improve the efficiency and safety of oHSVs.