Selectively oncolytic mutant of HSV-1 lyses HeLa cells mediated by Ras/RTN3

Yue Su, Huabin Zhu, Wei Xiao, Qin Xu, Lei Zhu, Xianrong Zhang, Qingwen Wan, Shumin Zhou, Enqi Du, Hua Xu, Lunguang Yao, Songya Lv, Baoli Hu, Yingle Liu, Yipeng Qi

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Abstract

The selectively oncolytic mtHSV, a HSV icp34.5 mutant with lacz gene insertion, was proved that it was targeted for treating tumors but not other organs, however, its oncolytic mechanism is under confirmation. The results showed that HeLa cells could be lysed efficiently by mtHSV in vitro. In the flow cytometry and Western blot experiment, Ras protein was obviously downregulated on plasma membrane (PM) while the whole Ras protein didn't change along with upregulation of reticulon 3(RTN3) protein at 48 h post infection of mtHSV in HeLa cells. Expression of Ras protein on PM and whole Ras protein in HeLa cells was downregulated by siFTa (inhibitor of α subunits of human farnesyltransferase with siRNA) and siRTN3(inhibitor of RTN3 with siRNA) respectively, and HeLa cells could be killed effectively by siFTa and siRTN3 at 48 h post transfection. So siFTa and siRTN3 effectively suppressed mtHSV infection of HeLa cells. Further, experiments were made to study the relationship between Ras and RTN3 using confocal colocalization and coimmunoprecipitation. The results exhibited that Ras could interact with RTN3 at endoplasmic reticulum. The data put forward that Ras/RTN3 is an important access to HeLa cells for mtHSV. The molecular interaction between Ras and RTN3 may further improve the understanding of the function of Ras and RTN3 in mtHSV infection. The results provide further theoretical evidence that mtHSV may be used as an oncolytic agent for cancer therapy.

Original languageEnglish (US)
Pages (from-to)202-208
Number of pages7
JournalCancer Biology and Therapy
Volume6
Issue number2
DOIs
StatePublished - Jan 1 2007

Fingerprint

Human Herpesvirus 1
HeLa Cells
ras Proteins
Small Interfering RNA
Down-Regulation
Infection
Cell Membrane
Farnesyltranstransferase
Lac Operon
Insertional Mutagenesis
Endoplasmic Reticulum
Transfection
Neoplasms
Flow Cytometry
Up-Regulation
Western Blotting
Proteins

Keywords

  • Herpes simplex virus type 1
  • Interaction
  • Oncolytic mechanism
  • Ras
  • Reticulon 3(RTN3)
  • mtHSV
  • siRNA

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

Cite this

Su, Y., Zhu, H., Xiao, W., Xu, Q., Zhu, L., Zhang, X., ... Qi, Y. (2007). Selectively oncolytic mutant of HSV-1 lyses HeLa cells mediated by Ras/RTN3. Cancer Biology and Therapy, 6(2), 202-208. https://doi.org/10.4161/cbt.6.2.3628

Selectively oncolytic mutant of HSV-1 lyses HeLa cells mediated by Ras/RTN3. / Su, Yue; Zhu, Huabin; Xiao, Wei; Xu, Qin; Zhu, Lei; Zhang, Xianrong; Wan, Qingwen; Zhou, Shumin; Du, Enqi; Xu, Hua; Yao, Lunguang; Lv, Songya; Hu, Baoli; Liu, Yingle; Qi, Yipeng.

In: Cancer Biology and Therapy, Vol. 6, No. 2, 01.01.2007, p. 202-208.

Research output: Contribution to journalArticle

Su, Y, Zhu, H, Xiao, W, Xu, Q, Zhu, L, Zhang, X, Wan, Q, Zhou, S, Du, E, Xu, H, Yao, L, Lv, S, Hu, B, Liu, Y & Qi, Y 2007, 'Selectively oncolytic mutant of HSV-1 lyses HeLa cells mediated by Ras/RTN3', Cancer Biology and Therapy, vol. 6, no. 2, pp. 202-208. https://doi.org/10.4161/cbt.6.2.3628
Su, Yue ; Zhu, Huabin ; Xiao, Wei ; Xu, Qin ; Zhu, Lei ; Zhang, Xianrong ; Wan, Qingwen ; Zhou, Shumin ; Du, Enqi ; Xu, Hua ; Yao, Lunguang ; Lv, Songya ; Hu, Baoli ; Liu, Yingle ; Qi, Yipeng. / Selectively oncolytic mutant of HSV-1 lyses HeLa cells mediated by Ras/RTN3. In: Cancer Biology and Therapy. 2007 ; Vol. 6, No. 2. pp. 202-208.
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abstract = "The selectively oncolytic mtHSV, a HSV icp34.5 mutant with lacz gene insertion, was proved that it was targeted for treating tumors but not other organs, however, its oncolytic mechanism is under confirmation. The results showed that HeLa cells could be lysed efficiently by mtHSV in vitro. In the flow cytometry and Western blot experiment, Ras protein was obviously downregulated on plasma membrane (PM) while the whole Ras protein didn't change along with upregulation of reticulon 3(RTN3) protein at 48 h post infection of mtHSV in HeLa cells. Expression of Ras protein on PM and whole Ras protein in HeLa cells was downregulated by siFTa (inhibitor of α subunits of human farnesyltransferase with siRNA) and siRTN3(inhibitor of RTN3 with siRNA) respectively, and HeLa cells could be killed effectively by siFTa and siRTN3 at 48 h post transfection. So siFTa and siRTN3 effectively suppressed mtHSV infection of HeLa cells. Further, experiments were made to study the relationship between Ras and RTN3 using confocal colocalization and coimmunoprecipitation. The results exhibited that Ras could interact with RTN3 at endoplasmic reticulum. The data put forward that Ras/RTN3 is an important access to HeLa cells for mtHSV. The molecular interaction between Ras and RTN3 may further improve the understanding of the function of Ras and RTN3 in mtHSV infection. The results provide further theoretical evidence that mtHSV may be used as an oncolytic agent for cancer therapy.",
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AU - Xiao, Wei

AU - Xu, Qin

AU - Zhu, Lei

AU - Zhang, Xianrong

AU - Wan, Qingwen

AU - Zhou, Shumin

AU - Du, Enqi

AU - Xu, Hua

AU - Yao, Lunguang

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AU - Hu, Baoli

AU - Liu, Yingle

AU - Qi, Yipeng

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AB - The selectively oncolytic mtHSV, a HSV icp34.5 mutant with lacz gene insertion, was proved that it was targeted for treating tumors but not other organs, however, its oncolytic mechanism is under confirmation. The results showed that HeLa cells could be lysed efficiently by mtHSV in vitro. In the flow cytometry and Western blot experiment, Ras protein was obviously downregulated on plasma membrane (PM) while the whole Ras protein didn't change along with upregulation of reticulon 3(RTN3) protein at 48 h post infection of mtHSV in HeLa cells. Expression of Ras protein on PM and whole Ras protein in HeLa cells was downregulated by siFTa (inhibitor of α subunits of human farnesyltransferase with siRNA) and siRTN3(inhibitor of RTN3 with siRNA) respectively, and HeLa cells could be killed effectively by siFTa and siRTN3 at 48 h post transfection. So siFTa and siRTN3 effectively suppressed mtHSV infection of HeLa cells. Further, experiments were made to study the relationship between Ras and RTN3 using confocal colocalization and coimmunoprecipitation. The results exhibited that Ras could interact with RTN3 at endoplasmic reticulum. The data put forward that Ras/RTN3 is an important access to HeLa cells for mtHSV. The molecular interaction between Ras and RTN3 may further improve the understanding of the function of Ras and RTN3 in mtHSV infection. The results provide further theoretical evidence that mtHSV may be used as an oncolytic agent for cancer therapy.

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