ADENOVIRAL-MEDIATED GENE-TRANSFER IN LYMPHOCYTES

Although adenovirus can infect a wide range of cell types, lymphocytes are not generally susceptible to adenovirus infection, in part becaus e of the absence of the expression of the cellular receptor for the ad enoviral fiber protein. The cellular receptor for adenovirus and coxsa ckievirus (CAR) recently was cloned and shown to mediate adenoviral en try by interaction with the viral fiber protein. We show that the ecto pic expression of CAR in various lymphocyte cell lines, which are almo st completely resistant to adenovirus infection, is sufficient to faci litate the efficient transduction of these cells by recombinant adenov iruses. Furthermore, this property of CAR does not require its cytopla smic domain, consistent with the idea that CAR primarily serves as a h igh affinity binding site for the adenoviral fiber protein, and that v iral entry is mediated by interaction of the viral penton base protein s with cellular integrins, As a demonstration of their functional util ity, we used CAR-expressing lymphocytes transduced with an adenovirus expressing Fas ligand to efficiently kill Fas receptor-expressing tumo r cells. The ability to efficiently manipulate gene expression in lymp hocyte cells by using adenovirus vectors should facilitate the functio nal characterization of pathways affecting lymphocyte physiology.