Meaghan Hancock, University of Guelph

Rebekah L Turner Casciato1, Nicole L Diggins1, Luke Slind1, Jennifer Mitchell1, Andrew H Pham1, Christopher J Parkins1, Wilma Perez1, Samuel Medica1, Michael Denton1, Takeshi F Andoh1, Gabriela M Webb2, Daniel Andrade-Vera1, Daniel N Streblow1,2, Patrizia Caposio1 and Meaghan H Hancock3 1Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, USA 2Division of Pathobiology and Immunology, Oregon National Primate Research Center, Beaverton, Oregon, USA 3Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON, Canada

Suppressing & Conquering

Herpesviruses and Poxviruses encode secreted chemokine binding proteins that prevent the interaction between chemokines and their cognate G protein coupled receptors to alter chemotactic gradients and intracellular signaling pathways. Human cytomegalovirus (HCMV) encodes the secreted protein UL22A (formerly UL21.5), which is described as a CCL5 (RANTES) binding protein and requires sulfation at two tyrosine residues (Y65 and Y69) for efficient RANTES interaction. We have shown that the UL22A protein, and the UL22A Y65 and Y69 residues are necessary for efficient HCMV reactivation from latency in CD34 hematopoietic progenitor cells and that UL22A expression is essential for reactivation in a humanized mouse model of latency. However, we were surprised to find that RANTES neutralization is not sufficient to complement the in vitro reactivation defect of UL22A mutant viruses. These data suggest that UL22A plays an important role in latency, possibly through interactions with additional chemokines or other types of ligands via its tyrosine residues, in order to mediate efficient HCMV reactivation.