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Archives of Virology

, Volume 164, Issue 5, pp 1271–1285 | Cite as

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

  • Catherine Paul
  • Lohit Khera
  • Rajeev KaulEmail author
Original Article

Abstract

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.

Notes

Acknowledgements

This work was supported by Grants from DBT, Ministry of Science and Technology (BT/PR15109/GBD/27/320/2011), a PURSE Grant from DST, and an R&D Grant from the University of Delhi. CP and LK received a Senior Research Fellowship funded by CSIR (09/045(1242)/2012-EMR-1 and 09/045(1135)/2011-EMR-1). This work also used original research material provided by Apath LLC for academic use via an ‘Academic Material Transfer Agreement’.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

705_2019_4151_MOESM1_ESM.pdf (582 kb)
Fig. S1 HCV Core expression in 293T cells promotes cancer cell migration and invasion by overcoming effect of metastasis suppressor Nm23-H1. 293T cells expressing the HCV core protein show significantly increased migration as compared to control cells. Overexpression of the HCV core protein can overcome the effect of metastasis suppressor Nm23-H1. Fig. S2 HCV Core expression in Huh7.5 cells promotes cancer cell migration and invasion by overcoming effect of metastasis suppressor Nm23-H1. Huh7.5 cells expressing the HCV core protein show significantly increased migration as compared to control cells. Overexpression of the HCV core protein can overcome the effect of metastasis suppressor Nm23-H1. (PDF 582 kb)

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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of MicrobiologyUniversity of DelhiNew DelhiIndia
  2. 2.Department of Molecular Cell BiologyWeizman Institute of ScienceRehovotIsrael

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