Induction of cytopathic effects and apoptosis in Spodoptera frugiperda cells by the HIV-1 Env glycoprotein signal peptide.
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.
Michalski
Chad James
CJ
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, University of Western Ontario, Siebens-Drake Research Institute, London, Ontario, Canada.
Li
Yan
Y
Kang
C Yong
CY
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000503:physiopathology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D021382:Protein Sorting Signals; D018411:Spodoptera / Q000166:cytology* / Q000821:virology
D015699:HIV Envelope Protein gp120; D021382:Protein Sorting Signals