title: Tanapoxvirus lacking a neuregulin-like gene regresses human melanoma tumors in nude mice.
abstract: 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.
authors.affiliation: Laboratory of Virology, Department of Biological Sciences, Western Michigan University, Kalamazoo, MI, 49008, USA.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Laboratory of Virology, Department of Biological Sciences, Western Michigan University, Kalamazoo, MI, 49008, USA.
authors.forename: Yogesh R
authors.initials: YR
authors.lastname: Suryawanshi
authors.affiliation: Laboratory of Virology, Department of Biological Sciences, Western Michigan University, Kalamazoo, MI, 49008, USA.
authors.forename: Dennis H
authors.initials: DH
authors.lastname: Kordish
authors.affiliation: Laboratory of Virology, Department of Biological Sciences, Western Michigan University, Kalamazoo, MI, 49008, USA.
authors.forename: Helene M
authors.initials: HM
authors.lastname: Woyczesczyk
authors.affiliation: Laboratory of Virology, Department of Biological Sciences, Western Michigan University, Kalamazoo, MI, 49008, USA.
authors.forename: David
authors.initials: D
authors.lastname: Jeng
authors.affiliation: Laboratory of Virology, Department of Biological Sciences, Western Michigan University, Kalamazoo, MI, 49008, USA. karim.essani@wmich.edu.
authors.forename: Karim
authors.initials: K
authors.lastname: Essani
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D008297:Male; D008545:Melanoma / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D051379:Mice; D008819:Mice, Nude; D020880:Neuregulins / Q000235:genetics*; D050130:Oncolytic Virotherapy / Q000379:methods; D050504:Oncolytic Viruses / Q000235:genetics*; D017384:Sequence Deletion; D047368:Tumor Burden; D014764:Viral Proteins / Q000235:genetics*; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays; D018158:Yatapoxvirus / Q000235:genetics*
chemical_list: D020880:Neuregulins; D014764:Viral Proteins
keywords: Melanoma; Neuregulin; Oncolytic virus; Tanapoxvirus; Thymidine kinase