Parvovirus nonstructural proteins induce an epigenetic modification through histone acetylation in host genes and revert tumor malignancy to benignancy.

in Journal of virology by Hiroyoshi Iseki, Rie Shimizukawa, Fumihiro Sugiyama, Satoshi Kunita, Atsushi Iwama, Masafumi Onodera, Hiromitsu Nakauchi, Ken-ichi Yagami

TLDR

  • Parvovirus infection can make cancer cells die or become less cancerous. The study found that the proteins inside the virus can make the cancer cells die or become less cancerous. The study also found that the virus can change the way the cancer cells work by making them more sticky and less likely to grow into a tumor. This could be useful for finding new ways to treat cancer.

Abstract

Several malignant tumor cells become apoptotic and revert to the benign phenotype upon parvovirus infection. Recently, we demonstrated that the rat parvovirus RPV/UT also induces apoptosis in the rat thymic lymphoma cell line C58(NT)D. However, a minority of cells that escaped apoptosis showed properties different from the parental cells, such as resistance to apoptosis, enhanced cell adherence, and suppressed tumorigenicity. The present study was performed to determine the molecular mechanism of parvovirus-induced phenotypic modification, including oncosuppression. We demonstrated that the nonstructural (NS) proteins of RPV/UT induced apoptosis in C58(NT)D cells and suppressed tumor growth in vivo. Interestingly, NS proteins induced the expression of ciliary neurotrophic factor receptor alpha, which is up-regulated in revertant cell clones, and enhanced histone acetylation of its gene. These results indicate that parvoviral NS regulate host gene expression through histone acetylation, suggesting a possible mechanism of oncosuppression.

Overview

  • The study investigates the effect of parvovirus infection on malignant tumor cells and their ability to revert to a benign phenotype. The hypothesis being tested is whether parvovirus infection can induce apoptosis in tumor cells and suppress tumor growth in vivo. The methodology used includes infecting the rat thymic lymphoma cell line C58(NT)D with the rat parvovirus RPV/UT and observing the effects on cell apoptosis and tumor growth. The primary objective of the study is to determine the molecular mechanism of parvovirus-induced phenotypic modification, including oncosuppression.

Comparative Analysis & Findings

  • The study found that parvovirus infection induced apoptosis in C58(NT)D cells and suppressed tumor growth in vivo. However, a minority of cells that escaped apoptosis showed properties different from the parental cells, such as resistance to apoptosis, enhanced cell adherence, and suppressed tumorigenicity. The study also identified that the nonstructural (NS) proteins of RPV/UT induced apoptosis in C58(NT)D cells and suppressed tumor growth in vivo. Interestingly, NS proteins induced the expression of ciliary neurotrophic factor receptor alpha, which is up-regulated in revertant cell clones, and enhanced histone acetylation of its gene. These results suggest that parvoviral NS regulate host gene expression through histone acetylation, which may be a possible mechanism of oncosuppression.

Implications and Future Directions

  • The study's findings suggest that parvovirus infection can induce apoptosis in tumor cells and suppress tumor growth in vivo. The identification of the molecular mechanism of parvovirus-induced phenotypic modification, including oncosuppression, may have significant implications for the development of new cancer therapies. Future research directions could include further investigation of the role of histone acetylation in parvovirus-induced oncosuppression and the development of targeted therapies that exploit this mechanism. Additionally, the study highlights the importance of understanding the complex interactions between viruses and cancer cells and the potential for viruses to be used as therapeutic agents in cancer treatment.
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