Tanapoxvirus lacking a neuregulin-like gene regresses human melanoma tumors in nude mice

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• 作者：Tiantian Zhang ; Yogesh R. Suryawanshi ; Dennis H. Kordish…
• 关键词：Tanapoxvirus ; Oncolytic virus ; Neuregulin ; Thymidine kinase ; Melanoma
• 刊名：Virus Genes
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：53
• 期：1
• 页码：52-62
• 全文大小：
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Medical Microbiology; Virology; Plant Sciences;
• 出版者：Springer US
• ISSN：1572-994X
• 卷排序：53

文摘

Neuregulin (NRG), an epidermal growth factor is known to promote the growth of various cell types, including human melanoma cells through ErbB family of tyrosine kinases receptors. Tanapoxvirus (TPV)-encoded protein TPV-15L, a functional mimic of NRG, also acts through ErbB receptors. Here, we show that the TPV-15L protein promotes melanoma proliferation. TPV recombinant generated by deleting the 15L gene (TPVΔ15L) showed replication ability similar to that of wild-type TPV (wtTPV) in owl monkey kidney cells, human lung fibroblast (WI-38) cells, and human melanoma (SK-MEL-3) cells. However, a TPV recombinant with both 15L and the thymidine kinase (TK) gene 66R ablated (TPVΔ15LΔ66R) replicated less efficiently compared to TPVΔ15L and the parental virus. TPVΔ15L exhibited more robust tumor regression in the melanoma-bearing nude mice compared to other TPV recombinants. Our results indicate that deletion of TPV-15L gene product which facilitates the growth of human melanoma cells can be an effective strategy to enhance the oncolytic potential of TPV for the treatment of melanoma.