REGULATORS OF APOPTOSIS ON THE ROAD TO PERSISTENT ALPHAVIRUS INFECTION

  • Griffin D
  • Hardwick A
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Abstract

Alphavirus infection can trigger the host cell to activate its genetically pro- grammed cell death pathway, leading to the morphological features of apop- tosis. The ability to activate this death pathway is dependent on both viral and cellular determinants. The more virulent strains of alphavirus induce apopto- sis with increased efficiency both in animal models and in some cultured cells. Although the immune system clearly plays a central role in clearing virus, the importance of other cellular factors in determining the outcome of virus infec- tions are evident from the observation that mature neurons are better able to resist alphavirus-induced apoptosis than immature neurons are, both in culture and in mouse brains. These findings are consistent with the age-dependent susceptibility to disease seen in animals. Cellular genes that are knownto regulate the cell death pathway can modulate the outcome of alphavirus infection in cultured cells and perhaps in animals. The cellular bax and bak genes, which are known to acceler- ate cell death, also accelerate virus-induced apoptosis. In contrast, inhibitors of apoptotic cell death such as bcl-2 suppress virus-induced apoptosis, which can facilitate a persistent virus infection. Thus, the balance of cellular factors that regulate cell death may be critical in virus infections. Additional viral factors also contribute to this balance. The more virulent strains of alphavirus have acquired the ability to induce apoptosis in mature neurons, while mature neurons are re- sistant to cell death upon infection with less virulent strains. Here we discuss a variety of cellular and viral factors that modulate the outcome of virus infection.

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Authors

  • Diane E. Griffin

  • and J. Marie Hardwick

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