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Alphaviruses and apoptosis.

Mei-Ling Li1, Victor Stollar

  • 1Department of Molecular Genetics, Microbiology and Immunology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854-5635, USA.

International Reviews of Immunology
|December 24, 2003
PubMed
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Sindbis virus (SV) and Semliki Forest virus (SFV) infection induce apoptosis, a process linked to neurovirulence. Viral RNA or proteins alone can trigger this cell death, involving mitochondrial and death receptor pathways.

Area of Science:

  • Virology
  • Cell Biology
  • Neuroscience

Background:

  • Sindbis virus (SV) and Semliki Forest virus (SFV) infections are known to induce apoptosis in cultured cells and the central nervous system (CNS) of mice.
  • Apoptosis induction and neurovirulence by these alphaviruses generally correlate and are age-dependent, with increased resistance observed in older individuals.

Purpose of the Study:

  • To elucidate the mechanisms and cellular pathways underlying alphavirus-induced apoptosis.
  • To investigate the role of viral components and cellular signaling in triggering programmed cell death during SV and SFV infections.

Main Methods:

  • Analysis of apoptosis induction in cultured cells and mouse CNS following SV/SFV infection.
  • Investigation of apoptosis triggered by viral RNA transfection and expression of specific viral proteins (e.g., nsP2).

Related Experiment Videos

  • Examination of cellular pathways, including mitochondrial and death receptor pathways, involved in alphavirus-induced apoptosis.

    • Main Results:

    • Viral infection, viral envelope proteins, or the nonstructural protein nsP2 can independently induce apoptosis.
    • Apoptosis can be triggered even without infectious viral particles, solely through transfection with viral RNA or RNA expressing nonstructural proteins.
    • Experimental evidence implicates both the mitochondrial and death receptor pathways in the cellular response to alphavirus infection.

    Conclusions:

    • Alphavirus-induced apoptosis is a complex process mediated by viral components and cellular signaling pathways.
    • The mitochondrial and death receptor pathways are key players in alphavirus-induced cell death.
    • The endoplasmic reticulum (ER) stress pathway does not appear to be involved in this process based on current findings.