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Inhibition of Translation Initiation by Protein 169: A Vaccinia Virus Strategy to Suppress Innate and Adaptive Immunity and Alter Virus Virulence


Long after smallpox was eradicated by vaccination with vaccinia virus, the study of this virus continues to reveal novel aspects of the interactions between a virus and the host in which it replicates. In this work we investigated the function of a previously uncharacterized VACV protein, called 169. The results show that protein 169 inhibits the synthesis of host proteins in cells and thereby provides a broad inhibition of the host innate immune response to infection. Unlike several other virus inhibitors of host protein synthesis, protein 169 acts by inhibiting the initiation of protein synthesis by both cap-dependent and cap-independent pathways. Also unlike several other virus protein synthesis inhibitors, the loss of protein 169 does not affect virus replication or spread, but the virus virulence was increased. This more severe infection is, however, cleared more rapidly and results in a stronger immunological memory response that is mediated by T-cells and provides better protection against re-infection. This work illustrates how shutting down host protein synthesis can be a strategy to block the host immune response to infection rather than a means to manufacture more virus particles.


Vyšlo v časopise: Inhibition of Translation Initiation by Protein 169: A Vaccinia Virus Strategy to Suppress Innate and Adaptive Immunity and Alter Virus Virulence. PLoS Pathog 11(9): e32767. doi:10.1371/journal.ppat.1005151
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005151

Souhrn

Long after smallpox was eradicated by vaccination with vaccinia virus, the study of this virus continues to reveal novel aspects of the interactions between a virus and the host in which it replicates. In this work we investigated the function of a previously uncharacterized VACV protein, called 169. The results show that protein 169 inhibits the synthesis of host proteins in cells and thereby provides a broad inhibition of the host innate immune response to infection. Unlike several other virus inhibitors of host protein synthesis, protein 169 acts by inhibiting the initiation of protein synthesis by both cap-dependent and cap-independent pathways. Also unlike several other virus protein synthesis inhibitors, the loss of protein 169 does not affect virus replication or spread, but the virus virulence was increased. This more severe infection is, however, cleared more rapidly and results in a stronger immunological memory response that is mediated by T-cells and provides better protection against re-infection. This work illustrates how shutting down host protein synthesis can be a strategy to block the host immune response to infection rather than a means to manufacture more virus particles.


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