Induction and prevention of apoptosis in human HEp-2 cells by herpes simplex virus type 1.

Abstract

Cultured human epithelial cells infected with an ICP27 deletion strain of herpes simplex virus type 1 (HSV-1) show characteristic features of apoptotic cells including cell shrinkage, nuclear condensation, and DNA fragmentation. These cells do not show such apoptotic features when infected with a wild-type virus unless the infections are performed in the presence of a protein synthesis inhibitor. Thus, both types of virus induce apoptosis, but the ICP27-null virus is unable to prevent this process from killing the cells. In this report, we show that this ICP27-deficient virus induced apoptosis in human HEp-2 cells through a pathway which involved the activation of caspase-3 and the processing of the death substrates DNA fragmentation factor and poly(ADP-ribose) polymerase. The induction of apoptosis by wild-type HSV-1 occurred prior to 6 h postinfection (hpi), and de novo viral protein synthesis was not required to induce the process. The ability of the virus to inhibit apoptosis was shown to be effective between 3 to 6 hpi. Wild-type HSV-1 infection was also able to block the apoptosis induced in cells by the addition of cycloheximide, staurosporine, and sorbitol. While U(S)3- and ICP22-deficient viruses showed a partial prevention of apoptosis, deletion of either the U(L)13 or vhs gene products did not affect the ability of HSV-1 to prevent apoptosis in infected cells. Finally, we demonstrate that in UV-inactivated viruses, viral binding and entry were not sufficient to induce apoptosis. Taken together, these results suggest that either gene expression or another RNA metabolic event likely plays a role in the induction of apoptosis in HSV-1-infected human cells.

• Authors: M Aubert, J O'Toole, J A Blaho
• Journal: Journal of virology (J Virol) Vol. 73 Issue 12 Pg. 10359-70 (Dec 1999) ISSN: 0022-538X [Print] United States
• PMID: 10559354 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Caspase Inhibitors
• Enzyme Inhibitors
• ICP22 protein, human herpesvirus 1
• ICP27 protein, human herpesvirus 1
• Immediate-Early Proteins
• Viral Proteins
• Viral Regulatory and Accessory Proteins
• herpes simplex virus, type 1 protein ICP4
• virion host shutoff protein, Simplexvirus
• EUS1 protein, Equine herpesvirus 1
• Sorbitol
• Protein Kinases
• UL13 protein, Simplexvirus
• Protein Serine-Threonine Kinases
• US3 protein, Human herpesvirus 1
• Ribonucleases
• CASP3 protein, human
• Caspase 3
• Staurosporine

Topics

• Animals
• Apoptosis
• Caspase 3
• Caspase Inhibitors
• Chlorocebus aethiops
• Enzyme Inhibitors (pharmacology)
• Gene Deletion
• Herpesvirus 1, Human (metabolism, physiology)
• Humans
• Immediate-Early Proteins (biosynthesis, genetics, physiology)
• Protein Kinases (genetics)
• Protein Serine-Threonine Kinases (genetics)
• Ribonucleases
• Sorbitol
• Staurosporine (pharmacology)
• Time Factors
• Tumor Cells, Cultured
• Vero Cells
• Viral Proteins (genetics)
• Viral Regulatory and Accessory Proteins