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Suppressive effect of elongation factor 2 on apoptosis induced by HIV-1 viral protein R

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Abstract

Rapid CD4+ lymphocyte depletion due to cell death caused by HIV infection is one of the hallmarks of acquired immunodeficiency syndrome. HIV-1 viral protein R (Vpr) induces apoptosis and is believed to contribute to CD4+ lymphocyte depletion. Thus, identification of cellular factors that potentially counteract this detrimental viral effect will not only help us to understand the molecular action of Vpr but also to design future antiviral therapies. In this report, we describe identification of elongation factor 2 (EF2) as such a cellular factor. Specifically, EF2 protein level is responsive to vpr gene expression; it is able to suppress Vpr-induced apoptosis when it is overproduced beyond its physiological level. EF2 was initially identified through a genome-wide multicopy suppressor search for Vpr-induced apoptosis in a fission yeast model system. Overproduction of fission yeast Ef2 completely abolishes Vpr-induced cell killing in fission yeast. Similarly, overexpression of the human homologue of yeast Ef2 in a neuroblastoma SKN-SH cell line and two CD4+ H9 and CEM-SS T-cell lines also blocked Vpr-induced apoptosis. The anti-apoptotic property of EF2 is demonstrated by its ability to suppress caspase 9 and caspase 3-mediated apoptosis induced by Vpr. In addition, it also reduces cytochrome c release induced by Vpr, staurosporine and TNFα. The fact that overproduction of EF2 blocks Vpr-induced cell death both in fission yeast and human cells, suggested that EF2 posses a highly conserved anti-apoptotic activity. Moreover, the responsive elevation of EF2 to Vpr suggests a possible host innate antiviral response.

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Author notes

  1. S. Zelivianski

    Present address: Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, 2205 Tech Dr. Hogan 2-100, Evanston, IL, 60208, USA

Authors and Affiliations

  1. Children's Memorial Research Center, Department of Pediatrics, Northwestern University Feinberg School of Medicine, 60614, Chicago, IL, USA

    S. Zelivianski, D. Liang, M. Chen, B. L. Mirkin & R. Y. Zhao

  2. Departments of Pathology and Microbiology-Immunology, University of Maryland School of Medicine, 10 South Pine Street, MSTF 700A, Baltimore, MD, 21201, USA

    D. Liang & R. Y. Zhao

  3. Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Feinberg School of Medicine, Chicago, USA

    B. L. Mirkin

  4. Departments of Pathology and Microbiology-Immunology, University of Maryland School of Medicine, 10 South Pine Street, MSTF 700A, Baltimore, MD, 21201-1192, USA

    R. Y. Zhao

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Correspondence to R. Y. Zhao.

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Zelivianski, S., Liang, D., Chen, M. et al. Suppressive effect of elongation factor 2 on apoptosis induced by HIV-1 viral protein R. Apoptosis 11, 377–388 (2006). https://doi.org/10.1007/s10495-006-4030-9

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  • DOI: https://doi.org/10.1007/s10495-006-4030-9

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