Characterization of the molecular mechanisms underlying
virus-host cell interactions

One of the most impressive features of herpesviruses is their abundance of viral proteins with clear sequence similarities to cellular counterparts. The current belief is that, over the million years of coevolution with their hosts, herpesviruses captured many cellular genes that they then extensively optimized to encode modern viral proteins that either imitate or inhibit the original cellular function, or, as in most cases, result in new functions that confer advantages to the virus.

In this regard, the Human Cytomegalovirus (HCMV) proves to be a master at capturing, duplicating, and shaping cellular genes to generate regulatory viral proteins able to interfere with many biochemical pathways and immune defense responses in the host, thereby promoting virus replication and persistence.
Of the numerous HCMV genes encoding proteins with signs of similarity to cellular proteins, the US12 gene family represents an astonishing example of this herpesviruses’ “capture and shape” evolutionary strategy. The US12 gene family in fact includes a set of 10 contiguous tandemly arranged genes (US12 to US21) evolved, through multiple duplication and divergence events, from an initially host-derived gene thought to have been captured by an ancestral primate CMV.

The US12 protein family is being studied in LMV to understand its importance at the interface of HCMV-host interactions. We use molecular genetics, molecular biology, biochemistry, proteomic, cell biology, and bioinformatic approaches to learn how the US12 proteins:
1. determine the HCMV’s ability to infect a wide variety of target cell-types;
2. dysregulate host-cell homeostasis to create a suitable cellular environment for virus replication;
3. counteract both intrinsic and innate antiviral responses.