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Journal of Virology, November 2004, p. 12297-12307, Vol. 78, No. 22
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.22.12297-12307.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Adenovirus E3-6.7K Protein Is Required in Conjunction with the E3-RID Protein Complex for the Internalization and Degradation of TRAIL Receptor 2

Drew L. Lichtenstein,1 Konstantin Doronin,2 Karoly Toth,2 Mohan Kuppuswamy,2 William S. M. Wold,2 and Ann E. Tollefson2*

VirRx Inc.,1 Department of Molecular Microbiology and Immunology, School of Medicine, Saint Louis University, St. Louis, Missouri2

Received 4 May 2004/ Accepted 23 June 2004

Adenoviruses (Ads) encode several proteins within the early region 3 (E3) transcription unit that help protect infected cells from elimination by the immune system. Among these immunomodulatory proteins, the receptor internalization and degradation (RID) protein complex, which is composed of the RID{alpha} (formerly E3-10.4K) and RIDß (formerly E3-14.5K) subunits, stimulates the internalization and degradation of certain members of the tumor necrosis factor (TNF) receptor superfamily, thus blocking apoptosis initiated by Fas and TNF-related apoptosis-inducing ligand (TRAIL). The experiments reported here show that TRAIL receptor 2 (TR2) is cleared from the cell surface in Ad-infected cells. Virus mutants containing deletions that span E3 were used to show that the RID and E3-6.7K proteins are both necessary for the internalization and degradation of TR2, whereas only the RID protein is required for TRAIL receptor 1 downregulation. In addition, replication-defective Ad vectors that express individual E3 proteins were used to establish that the RID and E3-6.7K proteins are sufficient to clear TR2. These data demonstrate that E3-6.7K is an important component of the antiapoptosis arsenal encoded by the E3 transcription unit of subgroup C Ads.


* Corresponding author. Mailing address: Department of Molecular Microbiology and Immunology, School of Medicine, Saint Louis University, 1402 South Grand Blvd., St. Louis, MO 63104. Phone: (314) 977-8863. Fax: (314) 977-8717. E-mail: tollefae{at}slu.edu.


Journal of Virology, November 2004, p. 12297-12307, Vol. 78, No. 22
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.22.12297-12307.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




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