Research ArticleVirulence

Attenuation of Rabies Virulence: Takeover by the Cytoplasmic Domain of Its Envelope Protein

Sci. Signal.  19 Jan 2010:
Vol. 3, Issue 105, pp. ra5
DOI: 10.1126/scisignal.2000510

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Tipping the Balance

Strains of rabies virus, which infects neurons, may be virulent, in which case the cells survive long enough for the virus to replicate and spread, or they may be attenuated, in which case the infected cells die by apoptosis. Préhaud et al. compared one attenuated and one virulent viral strain and found that a single amino acid change in a region of a viral envelope protein that binds to host cell proteins was sufficient to account for the death or survival of infected cells. The binding properties of the attenuated virus protein were expanded, thereby affecting the balance in the activities of host kinases and phosphatases sufficiently to trigger cell death. These findings may inform strategies to engineer attenuated viruses, which are often used in live vaccines.