Open AccessCoxsackie and adenovirus receptor (CAR)-dependent and major histocompatibility complex (MHC) class I-independent uptake of recombinant adenoviruses into human tumour cells
Author(s) -
Denise McDonald,
Luke H. Stockwin,
Torkjel Matzow,
Maria E. Blair Zajdel,
G. Eric Blair
Publication year - 1999
Publication title -
gene therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.332
H-Index - 159
eISSN - 1476-5462
pISSN - 0969-7128
DOI - 10.1038/sj.gt.3301006
Subject(s) - biology , chinese hamster ovary cell , mhc class i , major histocompatibility complex , virology , adenoviridae , mastadenovirus , cell culture , viral vector , microbiology and biotechnology , genetic enhancement , recombinant dna , antigen , immunology , gene , genetics
The role of two receptors, previously proposed to mediate the entry of adenoviruses into human cells, the coxsackie and adenovirus receptor (CAR) and the major histocompatibility complex (MHC) class I heavy chain has been investigated. The expression of MHC class I in many tumours is reduced or absent, therefore if this were a means by which adenoviruses gained entry into cells, it would have important implications for their application in cancer treatment. In order to determine if MHC class I heavy chain is involved in adenovirus type 5 (Ad5) uptake, the binding of recombinant Ad5 fibre knob domain (which mediates viral attachment) to human cell lines that had greatly different levels of surface MHC class I was studied. We also created derivatives of a non-permissive Chinese hamster ovary (CHO) cell line that expressed human class I (HLA-A2) and found that these cells did not bind fibre or take up virus. In addition, the extracellular domain of CAR was expressed in E. coli and used to generate a polyclonal anti-CAR antibody. This antibody blocked both 125I labelled fibre knob binding and virus uptake. Thus CAR, and not MHC class I, is a receptor for human adenoviruses in cultured tumour cells. Tissue CAR levels may therefore be an important factor in the efficiency of adenovirus-mediated gene therapy.