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Related Experiment Videos

ICP0 gene expression is a herpes simplex virus type 1 apoptotic trigger.

Christine M Sanfilippo1, John A Blaho

  • 1Department of Microbiology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029-6574, USA.

Journal of Virology
|July 1, 2006
PubMed
Summary

Herpes simplex virus type 1 (HSV-1) infection triggers apoptosis, a programmed cell death. The study identifies HSV-1 alpha0 gene expression as the sole viral factor initiating this cell death cascade, a novel finding in pathogen-host interactions.

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Area of Science:

  • Virology
  • Cell Biology
  • Molecular Biology

Background:

  • Apoptosis is a regulated cell death process crucial for development and in response to stimuli like viral infections.
  • Herpes simplex virus type 1 (HSV-1) is known to induce apoptosis but also inhibit it in infected cells.
  • The specific viral factor initiating apoptosis during HSV-1 infection remained largely unknown.

Purpose of the Study:

  • To identify the specific viral factor responsible for triggering apoptosis during HSV-1 infection.
  • To elucidate the role of viral immediate-early (IE) genes in initiating or preventing apoptosis.
  • To investigate the contribution of individual IE genes to the apoptotic process.

Main Methods:

  • Systematic evaluation of HSV-1 immediate-early (IE) genes (alpha27, alpha4, alpha22, alpha0) using deletion mutant viruses.

Related Experiment Videos

  • Assessing apoptosis induction by individual IE gene expression.
  • Utilizing a recombinant virus with a stop codon in the alpha0 gene to confirm the inducer.

    • Main Results:

    • HSV-1 receptor binding, DNA injection, and early gene expression steps preceding IE gene expression do not induce apoptosis.
    • HSV-1 IE genes alpha27, alpha4, and alpha22 are involved in preventing apoptosis, not inducing it.
    • Sole expression of the HSV-1 alpha0 gene was sufficient to trigger apoptosis, acting as an 'apoptoxin'.
    • The ICP0 protein itself was not the direct inducer; rather, alpha0 gene expression initiated the apoptotic cascade.

    Conclusions:

    • HSV-1 alpha0 gene expression is the initial trigger for apoptosis during HSV-1 infection.
    • This represents the first instance of a single viral gene product initiating apoptosis in infected cells.
    • Viral gene expression offers a unique mechanism for pathogens to manipulate host cell interactions.