Downregulation of human CD46 by adenovirus serotype 35 vectors.

Abstract

Human CD46 (membrane cofactor protein), which serves as a receptor for a variety of pathogens, including strains of measles virus, human herpesvirus type 6 and Neisseria, is rapidly downregulated from the cell surface following infection by these pathogens. Here, we report that replication-incompetent adenovirus (Ad) serotype 35 (Ad35) vectors, which belong to subgroup B and recognize human CD46 as a receptor, downregulate CD46 following infection. A decline in the surface expression of CD46 in human peripheral blood mononuclear cells was detectable 6 h after infection, and reached maximum (72%) 12 h after infection. Ad35 vector-induced downregulation of surface CD46 levels gradually recovered after the removal of Ad35 vectors, however, complete recovery of CD46 expression was not observed even at 96 h after removal. The surface expression of CD46 was also reduced after incubation with fiber-substituted Ad serotype 5 (Ad5) vectors bearing Ad35 fiber proteins, ultraviolet-irradiated Ad35, vectors and recombinant Ad35 fiber knob proteins; in contrast, conventional Ad5 vectors did not induce surface CD46 downregulation, suggesting that the fiber knob protein of Ad35 plays a crucial role in the downregulation of surface CD46 density. These results have important implications for gene therapy using CD46-utilizing Ad vectors and for the pathogenesis of Ads that interact with CD46.

• Authors: F Sakurai, K Akitomo, K Kawabata, T Hayakawa, H Mizuguchi
• Journal: Gene therapy (Gene Ther) Vol. 14 Issue 11 Pg. 912-9 (Jun 2007) ISSN: 0969-7128 [Print] England
• PMID: 17377598 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Membrane Cofactor Protein
• Green Fluorescent Proteins
• Luciferases

Topics

• Adenoviridae Infections (immunology)
• Adenoviruses, Human (genetics, immunology)
• Blotting, Western
• Cell Line, Tumor
• Down-Regulation
• Flow Cytometry
• Genetic Engineering
• Genetic Therapy (adverse effects, methods)
• Genetic Vectors (adverse effects, genetics)
• Green Fluorescent Proteins (genetics)
• Humans
• Luciferases (genetics)
• Membrane Cofactor Protein (analysis, genetics)
• Reverse Transcriptase Polymerase Chain Reaction