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Hepatitis C virus core protein interacts with cellular metastasis suppressor Nm23-H1 and promotes cell migration and invasion

Paul, Catherine, Khera, Lohit, Kaul, Rajeev
Archives of virology 2019 v.164 no.5 pp. 1271-1285
Hepatitis C virus, cell movement, etiological agents, genotype, hepatoma, humans, males, metastasis, neoplasm cells, sumoylation, transcription (genetics), viral core proteins
Hepatitis C virus (HCV) is the major etiological agent of hepatocellular carcinoma (HCC), which is the fourth most common cause of cancer-related deaths worldwide and second in terms of deaths of males (Bray et al. in CA Cancer J Clin 68(6):394–424, 2018). HCV-induced HCC is a multi-step process that involves alteration of several host regulatory pathways. One of the key features of HCV-associated hepatocellular carcinoma is the metastasis of cancer cells to different organs. Human Nm23-H1 is one of the best-studied metastasis suppressor proteins, and it has been shown to be modulated in many human cancers. Our study shows that the core protein of HCV genotype 2a can co-localize and interact directly with Nm23-H1 within cancer cells, resulting in modulation of the anti-metastasis properties of Nm23-H1. The HCV core protein promotes SUMOylation and degradation of the Nm23-H1 protein, as well as transcriptional downregulation. This study provides evidence that the HCV core protein is a pro-metastatic protein that can interact directly with and modulate the functions of cellular metastasis suppressor Nm23-H1.