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Title: Cytomegalovirus protein m154 perturbs the adaptor protein-1 compartment mediating broad-spectrum immune evasion
Author: Strazic Geljic, Ivana
Kucan Brlic, Paula
Angulo, Guillem
Brizic, Ilija
Lisnic, Berislav
Jenus, Tina
Juranic Lisnic, Vanda
Pietri, Gian Pietro
Engel Rocamora, Pablo
Kaynan, Noa
Zeleznjak, Jelena
Schu, Peter
Mandelboim, Ofer
Krmpotic, Astrid
Angulo Aguado, Ana
Jonjic, Stipan
Lenac Rovis, Tihana
Keywords: Infeccions per citomegalovirus
Cytomegalovirus infections
Issue Date: 13-Jan-2020
Publisher: eLife Sciences
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.
Note: Reproducció del document publicat a:
It is part of: eLife, 2020, vol. 9, num. e50803
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ISSN: 2050-084X
Appears in Collections:Articles publicats en revistes (Biomedicina)

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