Adenoviral-mediated gene transfer in lymphocytes

被引:125
作者
Leon, RP
Hedlund, T
Meech, SJ
Li, SB
Schaack, J
Hunger, SP
Duke, RC
DeGregori, J
机构
[1] Univ Colorado, Hlth Sci Ctr, Dept Biochem & Mol Genet, Ctr Canc, Denver, CO 80262 USA
[2] Univ Colorado, Hlth Sci Ctr, Dept Pediat, Ctr Canc,Div Hematol Oncol, Denver, CO 80262 USA
[3] Univ Colorado, Hlth Sci Ctr, Dept Med Med Oncol & Immunol, Ctr Canc, Denver, CO 80262 USA
[4] Univ Colorado, Hlth Sci Ctr, Dept Microbiol, Ctr Canc, Denver, CO 80262 USA
关键词
D O I
10.1073/pnas.95.22.13159
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Although adenovirus can infect a wide range of cell types, lymphocytes are not generally susceptible to adenovirus infection, in part because of the absence of the expression of the cellular receptor for the adenoviral fiber protein. The cellular receptor for adenovirus and coxsackievirus (CAR) recently was cloned and shown to mediate adenoviral entry by interaction with the viral fiber protein. We show that the ectopic expression of CAR in various lymphocyte cell lines, which are almost completely resistant to adenovirus infection, is sufficient to facilitate the efficient transduction of these cells by recombinant adenoviruses. Furthermore, this property of CAR does not require its cytoplasmic domain, consistent with the idea that CAR primarily serves as a high affinity binding site for the adenoviral fiber protein, and that viral entry is mediated by interaction of the viral penton base proteins with cellular integrins, As a demonstration of their functional utility, we used CAR-expressing lymphocytes transduced with an adenovirus expressing Fas ligand to efficiently kill Fas receptor-expressing tumor cells. The ability to efficiently manipulate gene expression in lymphocyte cells by using adenovirus vectors should facilitate the functional characterization of pathways affecting lymphocyte physiology.
引用
收藏
页码:13159 / 13164
页数:6
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