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

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

Izvornik
ELife (2050-084X) 9 (2020); PMID: 31928630, 10

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
CD8+ T cells ; PVR, CD155 ; adaptor protein-1, AP-1 ; cytomegalovirus, CMV ; immune evasion ; immunology ; infectious disease ; inflammation ; m154 protein ; microbiology ; virus

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA