Abstract
BackgroundHerpes simplex virus (HSV) can cause encephalitis. Its infected cell polypeptide 47 (ICP47), encoded by immediate-early gene US12, promotes immune escape. ICP47 was modified in the clinically approved oncolytic HSV (oHSV) T-Vec. However, transcription regulatory sequence (TRS) and transcription regulatory factor (TRF) of HSV US12 are seldom reported.MethodsPreviously, our laboratory isolated a new HSV strain named HSV-1-LXMW from a male patient with oral herpes in Beijing, China. Firstly, the genetic tree was used to analyze its genetic relationship. The US12 TRS and TRF in HSV-1-LXMW were found by using predictive software. Secondly, the further verification by the multi-sequence comparative analysis shown that the upstream DNA sequence of HSV US12 gene contained the conserved region. Finally, the results of literature search shown that the expression of transcription factors was related to the tissue affinity of HSV-1 and HSV-2, so as to increase the new understanding of the transcriptional regulation of HSV biology and oncolytic virus (OVs) therapy.ResultsHere we reported the transcriptional regulation region sequence of our new HSV-1-LXMW, and its close relationship with HSV-1-CR38 and HSV-1-17. Importantly we identified eight different kinds of novel TRSs and TRFs of HSV US12 for the first time, and found they are conserved among HSV-1 (c-Rel, Elk-1, Pax-4), HSV-2 (Oct-1, CF2-II, E74A, StuAp) or both HSVs (HNF-4). The TRFs c-Rel and Oct-1 are biologically functional respectively in immune escape and viral replication during HSV infection.ConclusionsOur findings have important implication to HSV biology, infection, immunity and oHSVs.
Highlights
Herpes simplex virus (HSV) can cause encephalitis
We summarized information about the HSV US12 genomic DNA transcription regulatory regions of our new strain and 11 other strains studied in this article (Table 1)
Phylogenetic analysis of HSV-1-LXMW and other 11 HSV strains Based on the gene US12 transcription regulatory region sequences in Table 1 of HSV-1-LXMW and other 11 HSV strains, including 8 HSV-1 strains (17, CR38, H129, SC16, KOS, Patton, E19 and F) and 3 HSV-2 strains (SD90e, HG52 and H1226), the phylogenetic analysis about the evolutionary relationship among HSV-1LXMW and other 11 HSV strains were performed
Summary
Herpes simplex virus (HSV) can cause encephalitis. Its infected cell polypeptide 47 (ICP47), encoded by immediate-early gene US12, promotes immune escape. ICP47 was modified in the clinically approved oncolytic HSV (oHSV) T-Vec. transcription regulatory sequence (TRS) and transcription regulatory factor (TRF) of HSV US12 are seldom reported. OVs treatment are different from conventional chemotherapy and radiotherapy, and could provide additional treatment strategies [7]. OVs are diverse in structure and biology, which spread among tumors with different kinetics and kill tumor cells through multiple mechanisms [8]. HSV, a member of the alpha-herpesviruses subfamily, which is an encapsulated DNA virus, offers particular benefits for use as a gene transfer vector, contains at least 120 kb of double-stranded DNA genome, encoding more than 70 genes [7, 12]. HSV1 is normally related to oral-facial infections and may cause encephalitis in severe cases, while HSV-2 mostly induces genital infections and could cause mother-to-child transmission [13, 14]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: 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.