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

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.

Human Immunodeficiency Virus-1 (HIV-1)-Mediated Apoptosis: New Therapeutic Targets

“…Replacing or removing this signal peptide resulted in decreased levels of apoptosis. This increase in apoptosis induced by the signaling peptide of Env was found to depend on the up-regulation of caspase 1 [99]. T cell apoptosis mediated by Env is due to impaired cytokine production, with Th1 cytokines such as IFN-g, IL-2 and IL-12 blocking apoptosis.…”