Oncotarget

Research Papers:

Marek’s disease virus oncoprotein Meq physically interacts with the chicken infectious anemia virus-encoded apoptotic protein apoptin

Andrew C. Brown, Vishwanatha R.A.P. Reddy, Joshua Lee and Venugopal Nair _

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Oncotarget. 2018; 9:28910-28920. https://doi.org/10.18632/oncotarget.25628

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Abstract

Andrew C. Brown2,*, Vishwanatha R.A.P. Reddy1,*, Joshua Lee3 and Venugopal Nair1

1Viral Oncogenesis Group, The Pirbright Institute, Pirbright, Surrey, GU24 0NF, UK

2Wellcome Trust Centre for Human Genetics, Oxford, OX3 7BN, UK

3Bristol University, Bristol, BS8 1TH, UK

*These authors contributed equally to this work

Correspondence to:

Venugopal Nair, email: venugopal.nair@pirbright.ac.uk

Keywords: Meq; apoptin; MDV; CAV; lymphoma

Received: March 21, 2018     Accepted: May 31, 2018     Published: June 22, 2018

ABSTRACT

Marek’s disease (MD) is a neoplastic disease of poultry caused by Marek’s disease virus (MDV), a highly contagious alphaherpesvirus. Meq, the major MDV oncoprotein, induces neoplastic transformation of T-cells through several mechanisms, including inhibition of apoptosis. In contrast, the chicken anemia virus (CAV)-encoded protein apoptin (VP3) is a powerful inducer of apoptosis of tumor cells, a property that is exploited for anticancer therapeutics. Although the molecular mechanisms of selective induction of tumor cell apoptosis by apoptin are not fully understood, its tumor cell–restricted nuclear translocation is thought to be important. Co-infection with MDV and CAV is common in many countries, CAV antigens are readily detectable in MD lymphomas, and the MDV-transformed T-lymphoblastoid cell lines such as MSB-1 is widely used for propagating CAV for vaccine production. As MDV-transformed cell lines express high levels of Meq, we examined here whether CAV-encoded apoptin interacts with Meq in these cells. Using immunofluorescence microscopy, we found that apoptin and Meq co-localize to the nucleus, and biochemical analysis indicated that the two proteins do physically interact. Using a combination of Meq mutagenesis and co-immunoprecipitation, we demonstrate that apoptin interacts with Meq within a region between amino acids 130 and 140. Results from the IncuCyte assay suggested that Meq inhibits apoptin-induced apoptosis activity. In summary, our findings indicate that Meq interacts with and inhibits apoptin. Insights into this novel interaction between Meq and apoptin will relevance for pathogenesis of coinfections of the two viruses and in CAV vaccine production using MDV-transformed cell lines.


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