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J. Biol. Chem., Vol. 278, Issue 2, 1086-1093, January 10, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/2/1086    most recent M205636200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Blanco, R. Articles by Ventoso, I. Search for Related Content PubMed PubMed Citation Articles by Blanco, R. Articles by Ventoso, I. Social Bookmarking                      What's this?

Cell Killing by HIV-1 Protease^*

Raquel Blanco^§, Luis Carrasco, and Iván Ventoso^¶

From the  Centro de Biología Molecular Severo Ochoa Consejo Superior Investigaciones Cientificas-Universidad Autónoma de Madrid and the ^¶ Centro Nacional de Biotecnología, CSIC, Departamento de Bioquímica y Biología Celular, Universidad Autónoma de Madrid, Cantoblanco 28049, Madrid, Spain

The human immunodeficiency virus protease (HIV-1 PR) was expressed both in the yeast Saccharomyces cerevisiae and in mammalian cells. Inducible expression of HIV-1 PR arrested yeast growth, which was followed by cell lysis. The lytic phenotype included loss of plasma membrane integrity and cell wall breakage leading to the release of cell content to the medium. Given that neither poliovirus 2A protease nor 2BC protein, both being highly toxic for S. cerevisiae, were able to produce similar effects, it seems that this lytic phenotype is specific of HIV-1 PR. Drastic alterations in membrane permeability preceded the lysis in yeast expressing HIV-1 PR. Cell killing and lysis provoked by HIV-1 PR were also observed in mammalian cells. Thus, COS7 cells expressing the protease showed increased plasma membrane permeability and underwent lysis by necrosis with no signs of apoptosis. Strikingly, the morphological alterations induced by HIV-1 PR in yeast and mammalian cells were similar in many aspects. To our knowledge, this is the first report of a viral protein with such an activity. These findings contribute to the present knowledge on HIV-1-induced cytopathogenesis.

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