Forced degradation of Fas inhibits apoptosis in adenovirus-infected cells

Abstract

DNA viruses have evolved elaborate mechanisms to overcome host antiviral defences. In adenovirus-infected cells, programmed cell death (apoptosis) induced by the cytokine tumour necrosis factor (TNF) is inhibited by several adenovirus-encoded proteins. Occupation of the cell-surface receptor Fas, a member of the TNF-receptor superfamily that is expressed on most cell types, triggers apoptosis of that cell. Here we show that the adenovirus RID (for receptor internalization and degradation) protein complex, which is an inhibitor of TNF-induced apoptosis, mediates internalization of cell-surface Fas and its destruction inside lysosomes within the cell. Fas has not previously been shown to be internalized and then degraded. RID also mediates internalization of the receptor for epidermal growth factor, but it does not affect the transferrin receptor or class I antigens of the major histocompatibility complex. Removal of Fas from the surface of adenovirus-infected cells expressing RID may allow infected cells to resist Fas-mediated cell death and thus promote their survival.

Adenoviral Infection Decreases Mortality from Lipopolysaccharide-Induced Liver Failure Via Induction of TNF-α Tolerance

“…Adenoviral proteins E3-10.4K and E3-14.5K form a receptor internalization and degradation complex that protects cells from apoptosis induced by signaling through Fas (52). This complex has been shown to associate with E3-6.7K protein and internalize two other death receptors (TNF-related apoptosis-inducing ligand-1 and TNF-related apoptosis-inducing ligand-2) belonging to the TNFR family (53).…”

Protéines Nef du VIH et K3/K5 du virus associé au sarcoma de Kaposi : des « parasites »de la voie d’endocytose

“…Les exemples de virus qui ont développé des systèmes d'induction d'internalisation de protéines membranaires sont plutôt rares. L'adénovirus humain constitue cependant un autre exemple de modulation de l'expression de récepteurs impliqués dans l'apoptose tels que Fas ou le récepteur de TRAIL [33,34]. Cette modulation passe aussi par l'expression de deux protéines virales appelées RID (receptor internalization and degradation) α et β (ou protéines E3 10.4K et 14.5K) qui avaient été initialement décrites pour induire l'internalisation du récepteur de l'EGF [35].…”

Adenovirus RID complex enhances degradation of internalized tumour necrosis factor receptor 1 without affecting its rate of endocytosis

“…1(b)], suggesting that RID and TNFR1 are able to interact on the cell surface, either directly or through an intermediate bridging molecule. On the other hand, transferrin receptor, which was shown previously not to be downregulated by RID (Carlin et al, 1989;Tollefson et al, 1998), did not co-immunoprecipitate with RIDb, thus providing a specificity control for the Western blot. RIDb(YF), which itself has a higher level of surface expression, co-immunoprecipitated more plasma-membrane TNFR1 than did wild-type (WT) RIDb [left panel of Fig.…”

“…Many of the immunomodulatory genes of adenovirus (Ad) are encoded in early region 3 (E3) (Fessler et al, 2004b;Horwitz, 2004). The E3 receptor internalization and degradation (RID) complex, composed of two RIDa and one RIDb subunits, downregulates a specific set of plasma-membrane receptors, including FAS (Shisler et al, 1997;Elsing & Burgert, 1998;Tollefson et al, 1998), tumour necrosis factor (TNF)-related apoptosis-inducing ligand receptor 1 (TRAIL-R1) (Benedict et al, 2001;Tollefson et al, 2001) and epidermal growth factor receptor (EGFR) (Carlin et al, 1989;Tollefson et al, 1991). Together with another E3 protein, E3/6.7K, RID also reduces the surface expression of TRAIL-R2 (Lichtenstein et al, 2004).…”