Cytomegalovirus protein m154 perturbs the adaptor protein-1 compartment mediating broad-spectrum immune evasion

Ivana Strazic Geljic, Paola Kucan Brlic, Guillem Angulo, Ilija Brizic, Berislav Lisnic, Tina Jenus, Vanda Juranic Lisnic, Gian Pietro Pietri, Pablo Engel, Noa Kaynan, Jelena Zeleznjak, Peter Schu, Ofer Mandelboim, Astrid Krmpotic, Ana Angulo, Stipan Jonjic*, Tihana Lenac Rovis

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Cytomegaloviruses (CMVs) are ubiquitous pathogens known to employ numerous immunoevasive strategies that significantly impair the ability of the immune system to eliminate the infected cells. Here, we report that the single mouse CMV (MCMV) protein, m154, downregulates multiple surface molecules involved in the activation and costimulation of the immune cells. We demonstrate that m154 uses its cytoplasmic tail motif, DD, to interfere with the adaptor protein-1 (AP-1) complex, implicated in intracellular protein sorting and packaging. As a consequence of the perturbed AP-1 sorting, m154 promotes lysosomal degradation of several proteins involved in T cell costimulation, thus impairing virus-specific CD8+ T cell response and virus control in vivo. Additionally, we show that HCMV infection similarly interferes with the AP-1 complex. Altogether, we identify the robust mechanism employed by single viral immunomodulatory protein targeting a broad spectrum of cell surface molecules involved in the antiviral immune response.

Original languageAmerican English
Article numbere50803
JournaleLife
Volume9
DOIs
StatePublished - Jan 2020

Bibliographical note

Publisher Copyright:
© Strazic Geljic et al.

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