Prostate Tumor Cells Infected with a Recombinant Influenza Virus Expressing a Truncated NS1 Protein Activate Cytolytic CD8 + Cells To Recognize Noninfected Tumor Cells
| العنوان: | Prostate Tumor Cells Infected with a Recombinant Influenza Virus Expressing a Truncated NS1 Protein Activate Cytolytic CD8 + Cells To Recognize Noninfected Tumor Cells |
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| المؤلفون: | Kouichiro Kawano, Naotake Tsuda, Constantin G. Ioannides, Clay L. Efferson, Estanislao Nistal-Villán, Dihua Yu, Adolfo García-Sastre, James L. Murray, Shankhar Sellappan |
| المصدر: | Journal of Virology. 80:383-394 |
| بيانات النشر: | American Society for Microbiology, 2006. |
| سنة النشر: | 2006 |
| مصطلحات موضوعية: | Gene Expression Regulation, Viral, viruses, Immunology, Orthomyxoviridae, CD8-Positive T-Lymphocytes, Viral Nonstructural Proteins, Biology, Lymphocyte Activation, urologic and male genital diseases, medicine.disease_cause, Microbiology, Transformation and Oncogenesis, Virus, Interferon, Virology, LNCaP, Tumor Cells, Cultured, Influenza A virus, medicine, Humans, Cytotoxic T cell, virus diseases, biology.organism_classification, Oncolytic virus, Insect Science, Cancer research, Interleukin 12, T-Lymphocytes, Cytotoxic, medicine.drug |
| الوصف: | Many viral oncolytic approaches against cancer are based on the ability of specific viruses to replicate in tumors expressing components of the constitutively activated Ras/mitogen-activated protein kinase (MAPK) pathways and/or inhibited or dysregulated alpha/beta interferon (IFN-α/β) response pathways. A major issue when considering these approaches is their applicability to tumors that lack activated Ras. To identify the effector mechanisms activated by oncolytic viruses, we investigated inhibition of proliferation of the prostate cancer line LNCap by the recombinant TR-NS1 influenza A virus, a genetically attenuated influenza A/PR8/34 virus expressing a truncated nonstructural protein (NS1) of 126 amino acids. LNCap cells lack constitutively activated MAPK, extracellular signal-regulated kinase (ERK), and p38 and are resistant to death by IFN-α. Truncation of the NS1 protein of influenza viruses is known to result in viral attenuation due to a reduced ability of the NS1 to inhibit the IFN-α/β response. Infection with TR-NS1 virus rapidly activated ERK-1 more than ERK-2 in LNCap cells. Importantly, TR-NS1 virus infection transiently inhibited cell proliferation and induced apoptosis in LNCap cells. Addition of peripheral blood mononuclear cells (PBMC) and interleukin 12 (IL-12) to TR-NS1 virus-infected LNCap cells (TR-NS1-LNCap) resulted in faster elimination of TR-NS1-LNCap cells compared with LNCap cells. Moreover, TR-NS1-LNCap cells induced IFN-γ in PBMC. The levels of IFN-γ were amplified by IL-12. TR-NS1-LNCap cells also induced tumor-lytic cytotoxic T lymphocytes (CTL). These CTL lysed noninfected LNCap cells in a CD8-dependent manner. Activation of cellular immunity to tumor cells by viruses is an intriguing effector pathway, which should be especially significant for elimination of human tumors that lack activated Ras. |
| تدمد: | 1098-5514 0022-538X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bdca3a61f54f6e68eeb450aff855b827 https://doi.org/10.1128/jvi.80.1.383-394.2006 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....bdca3a61f54f6e68eeb450aff855b827 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10985514 0022538X |
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