How does host cell translation change upon infection?
Host organisms undergo marked reprogramming of their transcriptome during infection. Common transcriptional activation programmes act as generic alarm signals and induce cytokine expression (Jenner & Young, 2005). The extent at which host transcription is affected depends on the nature of the pathogen. Extracellular infections lead to general transcriptional rearrange-ment of common stress responses, such as heat shock proteins, metabolic stress response, and ubiquitin (Lee & Young, 2013), whereas intracellular infections cause global shut-off of host mRNA translation, which cripples anti-pathogenic responses (Lemaitre & Girardin, 2013; Walsh et al., 2013). However, little is known about how translation is affected during the early stages of infection, particularly how infection changes the tRNA modification levels. It has recently been shown that physiological stress factors can alter tRNA modification levels (Alings, Sarin et al., 2015). This potentially leads to translational slowdown and upregulation of several stress response pathways, including expression of genes associated with proteotoxic stress (Nedialkova & Leidel, 2015).
Since infection constitutes a severe stress to the host, changes in tRNA modification levels and translation are expected. This hypothesis will be challenged by studying the early stages of infection in well-defined infection models, determining host tRNA modification levels and translation rates, and comparing infected cells to non-infected controls. This will be achieved by the combined use of state-of-the-art techniques, including nano-LC mass spectrometry and ribosome profiling.
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