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Journal of Virology, July 2006, p. 6378-6386, Vol. 80, No. 13
0022-538X/06/$08.00+0     doi:10.1128/JVI.02350-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Adenovirus RID{alpha}ß Complex Inhibits Lipopolysaccharide Signaling without Altering TLR4 Cell Surface Expression{dagger}

Fernando Delgado-Lopez1* and Marshall S. Horwitz1,2,{ddagger}

Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461,1 Department of Pediatrics, Division of Infectious Diseases, Albert Einstein College of Medicine, Bronx, New York 104612

Received 7 November 2005/ Accepted 10 April 2006

The transmembrane heterotrimer complex 10.4K/14.5K, also known as RID (for "receptor internalization and degradation"), is encoded by the adenovirus E3 region, and it down-regulates the cell surface expression of several unrelated receptors. We recently showed that RID expression correlates with down-regulation of the cell surface expression of the tumor necrosis factor (TNF) receptor 1 in several human cells. This observation provided the first mechanistic explanation for the inhibition of TNF alpha-induced chemokines by RID. Here we analyze the immunoregulatory activities of RID on lipopolysaccharide (LPS) and interleukin-1 beta (IL-1ß)-mediated responses. Although both signaling pathways are strongly inhibited by RID, the chemokines up-regulated by IL-1ß stimulation are only marginally inhibited. In addition, RID inhibits signaling induced by LPS without affecting the expression of the LPS receptor Toll-like receptor 4, demonstrating that RID need not target degradation of the receptor to alter signal transduction. Taken together, our data demonstrate the inhibitory effect of RID on two additional cell surface receptor-mediated signaling pathways involved in inflammatory processes. The data suggest that RID has intracellular targets that impair signal transduction and chemokine expression without evidence of receptor down-regulation.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Forchheimer Building, Room 411, Bronx, NY 10461. Phone: (718) 430-3625. Fax: (718) 430-8702. E-mail: delgado{at}aecom.yu.edu.

{dagger} Dedicated to the memory of Marshall S. Horwitz.

{ddagger} Deceased.

Journal of Virology, July 2006, p. 6378-6386, Vol. 80, No. 13
0022-538X/06/$08.00+0     doi:10.1128/JVI.02350-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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