Notes on #ISMBECCB Sunday Afternoon Sessions

Mapping the Strategies of Viruses Hijacking Human Host Cells: An Experimental and Computational Comparative Study by Jacques Colinge

Original Paper: Viral immune modulators perturb the human molecular network by common and unique strategies. Pichlmair et al. (2012)

Interesting use of tagged proteins with purification and mass spec to analyse the interactions between viral and host proteins. Many viruses target the same proteins, but there is specificity too.

Drilling down on HCV, USP19 is a major target of viral proteins. This protein promotes degradation of misfolded proteins, but it may also be able to detect non-host proteins in general.

Human proteins that are targeted by virusses are much more likely to be hubs of protein/protein interaction networks. As virus are often very small so can only target a small number of proteins, thus targetting the hubs may be efficient (at the cost of specificity of effect).

Multi-task learning for Host-Pathogen protein interactions by Meghana Kshirsagar

Many pathogens will use the same strategies, thus we can learn across different pathogens to find similarities between different host/pathogen pairs. Their working hypothesis is that pathogens will target the same pathways in the host.

This is formalised as a multi-task learning process: loss on the training set is regularized by the difference of pairwise pathway signatures. Technically, this is nice because it can incorporate unlabeled data or missing data (as long as you can compute signatures).

Paper Review: Dual Host-Virus Arms Races Shape an Essential Housekeeping Protein

Demogines, A., Abraham, J., Choe, H., Farzan, M., & Sawyer, S. (2013). Dual Host-Virus Arms Races Shape an Essential Housekeeping Protein PLoS Biology, 11 (5) DOI: 10.1371/journal.pbio.1001571

This paper is not really related to my research, but I always enjoy a good cell biology story. My review is thus mostly a retelling of what I think were the highlights of the story.

In wild rodent populations, the retrovirus MMTV and New World arenaviruses both exploit Transferrin Receptor 1 (TfR1) to enter the cells of their hosts. Here we show that the physical interactions between these viruses and TfR1 have triggered evolutionary arms race dynamics that have directly modified the sequence of TfR1 and at least one of the viruses involved.

What is most interesting is that TfR1 is a housekeeping gene involved in iron uptake, which is essential for survival. Thus, it is probably highly constrained in its defensive evolution as even a small loss of function can be deleterious for the host.

The authors looked at the specific residues which seem to mutate rapidly in rodent species and they map to known virus/protein contact regions (which are known from X-ray crystallography).

Interestingly, the same evolutionary patterns are visible in rodent species for which no known virus use this entry point. However (and this is cool) we can find viral fossils in the genome of these rodents (i.e., we can parts of the viral sequence in the genome, which indicate that somewhere in the evolutionary past of these animals, a retrovirus integrated into the genome).

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This process also explains why some viruses infect some species and not others: divergent evolution of the virus itself to catch up with the defensive evolution of different hosts makes them unable to infect across species. Thus, whenever the host mutates, it forces the virus gene to make an awkward choice: does it want to chase the new host surface and specialize to this species or let this species go as a possible target?