EPPISEmployee Personal and Professional Information System
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Followed by thorough biological experimentation such computational-based systems biology approaches will provide a unique tool to help decipher basic global principles of pathogenhost interaction and may reveal novel ePPIs amenable to therapeutic intervention.
The CRISPR/Cas9 approach has just started to reveal its power as a tool for unbiased identification of novel ePPIs, elegantly exemplified by the identification of CD300lf as the cell surface receptor for noroviruses, which, strikingly, was identified as the main determinant for the tropism of the murine norovirus [42].
It would be of interest to employ these libraries for unbiased identification of ePPIs. Notably, as mentioned above, we found that HAdV immunomodulators preferentially target other immunoreceptors that, similar lyto TIGIT, also play inhibitory functions [28], suggesting this might represent a common immunosuppressive tactic evolved by pathogens.
Characterizing host-pathogen ePPI networks is therefore of utmost importance to gain a better understanding of the infection process and to inform the development of novel or improved therapeutic strategies.
Excellent reviews have recently revisited the currently available technologies for proteome-wide ePPI discovery [4, 8, 53-55].
Recently, we applied this ePPI discovery platform to the study of extracellular viral proteins (Figure 1), with a focus on human adenovirus- (HAdV-) encoded immunomodulatory proteins [28].
Nevertheless, their inherent high throughput and compatibility with multivalent bait approaches makes them a powerful tool for ePPI discovery.
Although this study focused on identification of intracellular PPI, the applicability of the NAPPA-HaloTag technology for ePPI determination should be explored in the future.
Another MS-based approach that holds great promise for host-pathogen ePPI detection is the recently developed TRICEPS [33].
Notably, recent studies have revealed extensive ePPI networks in model organisms such as Drosophila or zebrafish [2, 9].
The development of powerful technologies for ePPI discovery has already illuminated sophisticated and sometimes unexpected molecular mechanisms by which pathogens interact with their hosts and has provided unique opportunities to increase our understanding of viral and bacterial pathogenesis.