Remarkably, 13.6K is encoded on the opposite strand of the essential E2B DNA polymerase and only found in primate adenoviruses. Thus, its birth required a novel alternative splicing event and the emergence of a de novo ORF without compromising the polymerase function! 7/8

We also describe how adenoviruses have evolved a new immunoevasin from scratch. We identified adenoviral i-leader/13.6K proteins as novel inhibitors of the TAP complex, which translocates cytosolic peptides to the MHC-I complex in the ER. 5/8

We discovered HHV7 U21 as a multifunctional immunoevasin. Not only does it inhibit MHC-I surface display (shown by the Ploegh lab) but it is also induces STING degradation. Thus, it suppresses both adaptive and innate immune responses with distinct domains. 4/8

The screens yielded MANY novel regulators of these pathways alongside previously known ones. A few highlights: We identified HHV6A U14 as a p53 antagonist that interacts with its DNA-binding domain in a similar manner to Large T antigen and inhibits p53 activation. 3/8