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Induction of cytopathic effects and apoptosis in Spodoptera frugiperda cells by the HIV-1 Env glycoprotein signal peptide

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Abstract

The loss of CD4+ T-cells in human immunodeficiency virus-infected individuals has been attributed not only to dysregulation of immune cell function but also direct and indirect killing mechanisms of both infected and bystander cells. This process proceeds through both necrotic and programmed cell death pathways. Several human immunodeficiency virus type 1 (HIV-1) gene products have been linked to the induction of cell death and apoptosis associated with virus infection. These include the Nef, Tat, Vpr, and Vpu proteins as well as the viral envelope glycoprotein. Our results now indicate that the signal peptide of HIV-1 is also involved in the induction of cytopathic effects leading to cell death. We have shown here that expression of HIV-1 gp120 or vesicular stomatitis virus G glycoprotein with the HIV-1 Env signal peptide resulted in a rapid induction of cytopathicity and cell death in S. frugiperda cells, whereas removal or replacement of the signal peptide ameliorated those effects. Further, our results show that cell death is induced, at least in part, through apoptotic pathways as characterized by evidence of nuclear condensation and DNA fragmentation, as well as by the activation of host-cell caspase activity. Our results indicate that the signal peptide of HIV-1 Env itself thus has a direct role in cellular cytotoxicity and the triggering of cell death pathways.

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Acknowledgment

This work was supported by grants from the Canadian Institutes of Health Research (CIHR) and Sumagen Canada Inc.

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Author notes

  1. Chad James Michalski

    Present address: Omnia Biologics, Inc, 12111 Parklawn Dr, Rockville, MD, 20850, USA

  2. Yan Li

    Present address: National Laboratory for Respiratory Viruses, Bureau of Microbiology, Canadian Science Centre for Human and Animal Health, 1015 Arlington Street, Winnipeg, MB, R3E 3R2, Canada

Authors and Affiliations

  1. Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, University of Western Ontario, Siebens-Drake Research Institute, London, Ontario, N6G 2V4, Canada

    Chad James Michalski, Yan Li & C. Yong Kang

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  1. Chad James Michalski
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Correspondence to C. Yong Kang.

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Michalski, C.J., Li, Y. & Kang, C.Y. Induction of cytopathic effects and apoptosis in Spodoptera frugiperda cells by the HIV-1 Env glycoprotein signal peptide. Virus Genes 41, 341–350 (2010). https://doi.org/10.1007/s11262-010-0527-y

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