Journal of Biosciences

, 44:10 | Cite as

Measles virus phosphoprotein inhibits apoptosis and enhances clonogenic and migratory properties in HeLa cells

  • Sankhajit Bhattacharjee
  • Rishi Kumar Jaiswal
  • Pramod Kumar YadavaEmail author


Measles virus is the causative agent of measles, a major cause of child mortality in developing countries. Two major proteins, coded by the viral genome, are nucleocapsid protein (N) and phosphoprotein (P). The N protein protects the viral genomic RNA and forms ribonucleoprotein complex (RNP) together with P protein. MeV-P protein recruits the large protein (L), i.e. viral RNA-depended RNA polymerase (RdRp), to ensure viral replication in host cell. Apoptogenic properties of N protein of Edmonston vaccine strain have been established in our lab previously. We investigated the role of MeV-P protein of Edmonston vaccine strain as modulator of apoptosis in cervical cancer cell line (HeLa) and found that MeV-P protein is anti-apoptotic and enhances cell proliferation. Measles virus is considered to be innately oncotropic virus. However, the anti-apoptotic property of MeV-P protein raises important concerns while adopting this virus as an anti-cancer therapeutic tool.


Anti-apoptosis cell migration clonogenicity, HeLa cells measles virus phosphoprotein Vimentin 



measles virus


measles virus phosphopreotein


measles virus nucleocapsid protein




N-terminal domain of MeV-P


C-terminal domain of MeV-P


reactive oxygen species


urokinase like plasminogen activator



We are thankful to Prof Martin Billeter for providing the plasmids. We thank Mrs Sarika Gupta for expert assistance with the flow cytometry experiments. Our study was supported by grants, which were received from UGC and DST, India. SB is the recipient of a Senior Research Fellowship of UGC.


  1. Aref S, Bailey K and Fielding A 2016 Measles to the rescue: a review of oncolytic measles virus. Viruses 8 pii:E294CrossRefGoogle Scholar
  2. Azmi AS and Mohammad RM 2009 Non-peptidic small molecule inhibitors against Bcl-2 for cancer therapy. J. Cell Physiol. 218 13–21CrossRefGoogle Scholar
  3. Azmi AS, Wang Z, Philip PA, Mohammad RM and Sarkar FH 2011 Emerging Bcl-2 inhibitors for the treatment of cancer. Expert Opin. Emerg. Drugs 16 59–70CrossRefGoogle Scholar
  4. Bankamp B, Horikami SM, Thompson PD, Huber M, Billeter M and Moyer SA 1996 Domains of the measles virus N protein required for binding to P protein and self-assembly. Virology 216 272–277CrossRefGoogle Scholar
  5. Bhaskar A, Bala J, Varshney A and Yadava, P 2011 Expression of measles virus nucleoprotein induces apoptosis and modulates diverse functional proteins in cultured mammalian cells. PLoS ONE 6 e18765CrossRefGoogle Scholar
  6. Caignard G, Bourai M, Jacob Y, Tangy F and Vidalain PO 2009 Inhibition of IFN-alpha/beta signaling by two discrete peptides within measles virus V protein that specifically bind STAT1 and STAT2. Virology 383 112–120CrossRefGoogle Scholar
  7. Caignard G, Guerbois M, Labernardiere JL, Jacob Y, Jones LM, Wild F, Tangy F and Vidalain PO 2007 Measles virus V protein blocks Jak1-mediated phosphorylation of STAT1 to escape IFN-alpha/beta signalling. Virology 368 351–362CrossRefGoogle Scholar
  8. Chen M, Cortay JC and Gerlier D 2003 Measles virus protein interactions in yeast: new findings and caveats. Virus Res. 98 123–129CrossRefGoogle Scholar
  9. Colucci-Guyon E, Portier MM, Dunia I, Paulin D, Pournin S and Babinet C 1994 Mice lacking vimentin develop and reproduce without an obvious phenotype. Cell 79 679–694CrossRefGoogle Scholar
  10. Cox R and Plemper PK 2015 The paramyxovirus polymerase complex as a target for next-generation anti-paramyxovirus therapeutics. Front. Microbiol. 6 459CrossRefGoogle Scholar
  11. Curran J 1996 Reexamination of the Sendai virus P protein domains required for RNA synthesis: a possible supplemental role for the P protein. Virology 221 130–140CrossRefGoogle Scholar
  12. Curran J, Marq JB and Kolakofsky D 1995 An N-terminal domain of the Sendai paramyxovirus P protein acts as a chaperone for the NP protein during the nascent chain assembly step of genome replication. J. Virol. 69 849–855PubMedPubMedCentralGoogle Scholar
  13. Curran J, Pelet T and Kolakofsky D 1994 An acidic activation-like domain of the Sendai virus P protein is required for RNA synthesis and encapsidation. Virology 202 875–884CrossRefGoogle Scholar
  14. Devaux P, Von Messling V, Songsungthong W, Springfeld C and Cattaneo R 2007 Tyrosine 110 in the measles virus P protein is required to block STAT1 phosphorylation. Virology 360 72–83CrossRefGoogle Scholar
  15. Dimmeler S, Breitschopf K, Haendeler J and Zeiher AM 1999 Dephosphorylation targets Bcl-2 for ubiquitin-dependent degradation: a link between the apoptosome and the proteasome pathway. J. Exp. Med. 189 1815–1822CrossRefGoogle Scholar
  16. Dowling PC, Blumberg BM, Menonna J, Adamus JE, Cook P, Crowley JC, Kolakofsky D and Cook SD 1986 Transcriptional map of the measles virus genome. J. Gen. Virol. 67 1987–1992CrossRefGoogle Scholar
  17. Du TA 2013 Cell death: balance through a bivalent regulator. Nat. Rev. Mol. Cell Biol. 14 546CrossRefGoogle Scholar
  18. Goldman RD, Khuon S, Chou YH, Opal P and Steinert PM 1996 The function of intermediate filaments in cell shape and cytoskeletal integrity. J. Cell Biol. 134 971–983CrossRefGoogle Scholar
  19. Hanahan D and Weinberg RA 2000 The hallmarks of cancer. Cell 100 57–70CrossRefGoogle Scholar
  20. Hanahan D and Weinberg RA 2011 Hallmarks of cancer: the next generation. Cell 144 646–674CrossRefGoogle Scholar
  21. Holzmann H, Hengel H, Tenbusch M and Doerr HW 2016 Eradication of measles: remaining challenges. Med. Microbiol. Immunol. 205 201–208CrossRefGoogle Scholar
  22. Ito M, Yamamoto T, Watanabe M, Ihara T, Kamiya H and Sakurai M 1996 Detection of measles virusinduced apoptosis of human monocytic cell line (THP-1) by DNA fragmentation ELISA. FEMS Immunol. Med. Microbiol. 15 115–22CrossRefGoogle Scholar
  23. Iwasa T, Suga S, Qi L and Komada Y 2010 Apoptosis of human peripheral blood mononuclear cells by wild-type measles virus infection is induced by interaction of hemagglutinin protein and cellular receptor, SLAM via caspase-dependent pathway. Microbiol. Immunol. 54 405–416PubMedGoogle Scholar
  24. Jankun J and Skrzypczak-Jankun E 1999 Molecular basis of specific inhibition of urokinase plasminogen activator by amiloride. Cancer Biochem. Biophys. 17 109–123PubMedGoogle Scholar
  25. Katsumoto T, Mitsushima A and Kurimura T 1990 The role of the vimentin intermediate filaments in rat 3Y1 cells elucidated by immunoelectron microscopy and computergraphic reconstruction. Biol. Cell 68 139–146CrossRefGoogle Scholar
  26. Kerr JF 1965 A histochemical study of hypertrophy and ischaemic injury of rat liver with special reference to changes in lysosomes. J. Pathol. Bacteriol. 90 419–435CrossRefGoogle Scholar
  27. Li B and Dou QP 2000 Bax degradation by the ubiquitin/proteasome-dependent pathway: involvement in tumor survival and progression. Proc. Natl. Acad. Sci. USA 97 3850–3855CrossRefGoogle Scholar
  28. Longhi S, Receveur-Bréchot V, Karlin D, Johansson K, Darbon H, Bhella D, Yeo R, Finet S and Canard B 2003 The C-terminal domain of the measles virus nucleoprotein is intrinsically disordered and folds upon binding to the C-terminal moiety of the phosphoprotein. J. Biol. Chem. 278 18638–18648CrossRefGoogle Scholar
  29. Masood A, Azmi AS and Mohammad RM 2011 Small molecule inhibitors of bcl-2 family proteins for pancreatic cancer therapy. Cancers (Basel) 3 1527–1549CrossRefGoogle Scholar
  30. Ohno S, Ono N, Takeda M, Takeuchi K and Yanagi Y 2004 Dissection of measles virus V protein in relation to its ability to block alpha/beta interferon signal transduction. J. Gen. Virol. 85 2991–2999CrossRefGoogle Scholar
  31. Takeuchi K, Kadota SI, Takeda M, Miyajima N and Nagata K 2003 Measles virus V protein blocks interferon (IFN)-alpha/beta but not IFN-gamma signaling by inhibiting STAT1 and STAT2 phosphorylation. FEBS Lett. 545 177–182CrossRefGoogle Scholar
  32. Yokota S, Okabayashi T, Yokosawa N and Fujii N 2008 Measles virus P protein suppresses Toll-like receptor signal through up-regulation of ubiquitin-modifying enzyme A20. FASEB J. 22 74–83CrossRefGoogle Scholar
  33. Zhao D, Chen P, Yang H, Wu Y, Zeng X, Zhao Y, Wen Y, Zhao X, Liu X, Wei Y and Li Y 2012 Live attenuated measles virus vaccine induces apoptosis and promotes tumour regression in lung cancer. Oncol. Rep. 29 199–204CrossRefGoogle Scholar

Copyright information

© Indian Academy of Sciences 2019

Authors and Affiliations

  • Sankhajit Bhattacharjee
    • 1
  • Rishi Kumar Jaiswal
    • 1
  • Pramod Kumar Yadava
    • 1
    Email author
  1. 1.Applied Molecular Biology Laboratory, School of Life SciencesJawaharlal Nehru UniversityNew DelhiIndia

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