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Replication-Defective HSV-1 Effectively Targets Trigeminal Ganglion and Inhibits Viral Pathopoiesis by Mediating Interferon Gamma Expression in SH-SY5Y Cells

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Abstract

It has been widely believed that recurrence of herpes simplex keratitis (HSK) is due to the reactivation of herpes simplex virus type 1 (HSV-1) from latent sites in trigeminal ganglion (TG). However, there are also not effective vectors which could target TG for therapy. Replication-defective HSV-1 vector (rdHSV-IFNγ) was established by calcium phosphate co-transfection of complementing cells. We firstly infected rdHSV-IFNγ to SH-SY5Y, and detected IFNγ expression by western blot, evaluated 50 % cellular cytotoxicity (CC50) by ELISA. Antiviral activity of rdHSV-IFNγ was examined by immunofluorescence and antiviral concentration of 50 % effectiveness (EC50) assay. The rdHSV-IFNγ vector was immunized to Wistar rats to observe targeting function to TG. Kaplan–Meier survival analysis was utilized to assess security of rdHSV-IFNγ. RT-PCR and immunohistochemistry assay were employed to detect rdHSV-IFNγ localization in TG. Western blot was employed to detect IFNγ expression. rdHSV-IFNγ was successfully established, and performed an effective antiviral activity and higher security in SH-SY5Y. There were no significant differences of survival and corneal infection rate of rdHSV-IFNγ immunized rats among groups (P > 0.05). RT-PCR and immunohistochemistry indicated that expression of glycoprotein D (gD) in TG could target TG and decreased following with times post immunization. Furthermore, IFNγ was expressed effectively in TG tissues. Our findings indicated that established rdHSV-IFNγ vector effectively transported therapeutic gene into TG tissues. The administration of replication-defective vector carrying therapeutic genes may become a promising tool in inhibition or reoccurrence of HSK in clinical.

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Acknowledgements

This research was supported by Science and Technology Research and Development Program of Shaanxi Province of China (Grant No. 2011 K12-55).

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We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Ophthalmology, No. 1 Hospital of Xi’an, Xi’an, 710002, China

    Kun Xu, Xian-Ning Liu, Hong-Bing Zhang, Na An, Yao Wang & Ya-Ni Wang

  2. Shaanxi Provincial Key Laboratory of Ophthalmology, Ophthalmological Institute of Shaanxi Province, Fen Road 30, South Street, Xi’an, 710002, Shaanxi Province, China

    Kun Xu, Xian-Ning Liu, Na An, Yao Wang & Ya-Ni Wang

  3. Institute of Neurobiology, Medical School of Xi’an Jiaotong University, Xi’an, 710061, China

    Zhi-Chao Zhang

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  1. Kun Xu
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  2. Xian-Ning Liu
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  3. Hong-Bing Zhang
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  4. Na An
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  5. Yao Wang
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  7. Ya-Ni Wang
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Correspondence to Kun Xu.

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Xu, K., Liu, XN., Zhang, HB. et al. Replication-Defective HSV-1 Effectively Targets Trigeminal Ganglion and Inhibits Viral Pathopoiesis by Mediating Interferon Gamma Expression in SH-SY5Y Cells. J Mol Neurosci 53, 78–86 (2014). https://doi.org/10.1007/s12031-013-0199-x

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  • DOI: https://doi.org/10.1007/s12031-013-0199-x

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