The extracellular interactome of the human adenovirus family reveals diverse strategies for immunomodulation

Nadia Martinez-Martin, Sree R. Ramani, Jason A. Hackney, Irene Tom, Bernd J. Wranik, Michelle Chan, Johnny Wu, Maciej T. Paluch, Kentaro Takeda, Philip E. Hass, Hilary Clark and Lino C. Gonzalez ()
Additional contact information
Nadia Martinez-Martin: Genentech
Sree R. Ramani: Genentech
Jason A. Hackney: Genentech
Irene Tom: Genentech
Bernd J. Wranik: Genentech
Michelle Chan: Genentech
Johnny Wu: Genentech
Maciej T. Paluch: Genentech
Kentaro Takeda: Genentech
Philip E. Hass: Genentech
Hilary Clark: Genentech
Lino C. Gonzalez: Genentech

Nature Communications, 2016, vol. 7, issue 1, 1-16

Abstract: Abstract Viruses encode secreted and cell-surface expressed proteins essential to modulate host immune defenses and establish productive infections. However, to date there has been no systematic study of the extracellular interactome of any human virus. Here we utilize the E3 proteins, diverse and rapidly evolving transmembrane-containing proteins encoded by human adenoviruses, as a model system to survey the extracellular immunomodulatory landscape. From a large-scale protein interaction screen against a microarray of more than 1,500 human proteins, we find and validate 51 previously unidentified virus–host interactions. Our results uncover conserved strategies as well as substantial diversity and multifunctionality in host targeting within and between viral species. Prominent modulation of the leukocyte immunoglobulin-like and signalling lymphocyte activation molecule families and a number of inhibitory receptors were identified as hubs for viral perturbation, suggesting unrecognized immunoregulatory strategies. We describe a virus–host extracellular interaction map of unprecedented scale that provides new insights into viral immunomodulation.

Date: 2016
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DOI: 10.1038/ncomms11473

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