Artículo
Analysis of the role of autophagy inhibition by two complementary human cytomegalovirus BECN1/Beclin 1-binding proteins
Mouna, Lina; Hernandez, Eva; Bonte, Dorine; Brost, Rebekka; Amazit, Larbi; Delgui, Laura Ruth
; Brune, Wolfram; Geballe, Adam P.; Beau, Isabelle; Esclatine, Audrey
![Icon](/themes/CONICETDigital/images/conicet.png)
Fecha de publicación:
12/2015
Editorial:
Landes Bioscience
Revista:
Autophagy
ISSN:
1554-8627
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Autophagy is activated early after human cytomegalovirus (HCMV) infection, but lateron the virus blocks autophagy. Here we characterized 2 HCMV proteins, TRS1 andIRS1, which inhibit autophagy during infection. Expression of either TRS1 or IRS1 wasable to block autophagy in different cell lines, independently of the EIF2S1 kinase,EIF2AK2/PKR. Instead, TRS1 and IRS1 interacted with the autophagy proteinBECN1/Beclin 1. We mapped the BECN1-binding domain (BBD) of IRS1 and TRS1 andfound it to be essential for autophagy inhibition. Mutant viruses that express only IRS1or TRS1 partially controlled autophagy, whereas a double mutant virus expressingneither protein stimulated autophagy. A mutant virus that did not express IRS1 andexpressed a truncated form of TRS1 in which the BBD was deleted, failed to controlautophagy. However, this mutant virus had similar replication kinetics as wild-type virus,suggesting that autophagy inhibition is not critical for viral replication. In fact, usingpharmacological modulators of autophagy and inhibition of autophagy by shRNAknockdown, we discovered that stimulating autophagy enhanced viral replication.Conversely, inhibiting autophagy decreased HCMV infection. Thus, our resultsdemonstrate a new proviral role of autophagy for a DNA virus
Palabras clave:
Autophagy
,
Becn1
,
Cytomegalovirus
,
Eif2ak2/Pkr
,
Irs1
,
Trs1
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Identificadores
Colecciones
Articulos(IHEM)
Articulos de INST. HISTOLOGIA Y EMBRIOLOGIA DE MEND DR.M.BURGOS
Articulos de INST. HISTOLOGIA Y EMBRIOLOGIA DE MEND DR.M.BURGOS
Citación
Mouna, Lina; Hernandez, Eva; Bonte, Dorine; Brost, Rebekka; Amazit, Larbi; et al.; Analysis of the role of autophagy inhibition by two complementary human cytomegalovirus BECN1/Beclin 1-binding proteins; Landes Bioscience; Autophagy; 12; 2; 12-2015; 327-342
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