Abstract
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.
Highlights
Cancer is a major threat to human health
herpes simplex virus (HSV)-1-LXMW Is Evolutionarily Close to HSV-1 Strains F, H129, and SC16 Based on UL27 DNA Sequence Analysis
A phylogenetic analysis was performed to analyze the evolutionary relationship among the 11 HSV-1 strains
Summary
Cancer is a major threat to human health. Cancer stem cells play an important role in cancer initiation, progression, and drug resistance [1,2,3,4,5]. Oncolytic viruses (OVs) are spontaneously occurring or genetically modified viruses that preferentially infect and kill cancer cells, including cancer stem cells [6,7,8]. An oncolytic adenovirus with an E1B deletion, H101, or Oncorine R , was approved to treat cancer in China in 2005, which is the first clinical OV in the world [9]. OVs, including the measles virus (MV), Newcastle disease virus (NDV), herpes simplex virus (HSV), reovirus, adenoviruses, and vesicular stomatitis virus (VSV), provide promising approaches in cancer treatment [10]. In 2015, the U.S Food and Drug Administration (FDA) approved T-vec, an oncolytic HSV that was engineered with deletions of genes γ34.5 and US12 (encoding ICP47) and subsequent insertion of the gene encoding human granulocyte macrophage colonystimulating factor (GM-CSF), to treat melanoma [12]. Oncolytic HSVs (oHSVs) have been made by engineering envelope glycoproteins [13]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
