Technologies for Proteome-Wide Discovery of Extracellular Host-Pathogen Interactions

Martinez-Martin, Nadia

Remarkably, many of the HAdV E3 proteins preferentially interacted with host receptors that exert known or predicted inhibitory functions during the immune response (as defined by the presence of intracellular immunoreceptor tyrosinebased inhibitory motif, ITIM), including LILRB1 [81, 82] , LAIR1 [83] , and MPZL1 [84] , suggesting previously unrecognized strategies of immunosuppression that may be utilized by other human pathogens [28] . Moreover, several of the receptors identified as targets for the viral proteins in this study (including the prominent cell surface molecule CD45) do not have known counterreceptors in the host, supporting the longstanding hypothesis that pathogen molecules drive the evolution of immune receptors and in many instances may represent the most relevant modulators of host receptor function [85] [86] [87] . In summary, such unbiased, microarraybased study of immunomodulatory proteins represented the first large-scale analysis of the PPI landscape of a collection of extracellular immunomodulators encoded by viruses. Future investigation of other pathogen-encoded molecules using similar extracellular protein microarrays will likely shape our understanding of the pathogen imprint in our immune system.