title: Influence of cell physiological state on gene delivery to T lymphocytes by chimeric adenovirus Ad5F35.
abstract: Adoptive transfer of genetically-modified T cells is a promising approach for treatment of both human malignancies and viral infections. Due to its ability to efficiently infect lymphocytes, the chimeric adenovirus Ad5F35 is potentially useful as an immunotherapeutic for the genetic modification of T cells. In previous studies, it was found that the infection efficiency of Ad5F35 was significantly increased without enhanced expression of the viral receptor after T cell stimulation; however, little is known about the underlying mechanism. Nonetheless, cell physiology has long been thought to affect viral infection. Therefore, we aimed to uncover the physiologic changes responsible for the increased infection efficiency of Ad5F35 following T cell stimulation. Given the complexity of intracellular transport we analyzed viral binding, entry, and escape using a Jurkat T cell model and found that both cell membrane fluidity and endosomal escape of Ad5F35 were altered under different physiological states. This, in turn, resulted in differences in the amount of virus entering cells and reaching the cytoplasm. These results provide additional insight into the molecular mechanisms underlying Ad5F35 infection of T cells and consequently, will help further the clinical application of genetically-modified T cells for immunotherapy.
authors.affiliation: Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guang dong Pharmaceutical University, Guang zhou, People's Republic of China.|School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guang zhou, People's Republic of China.
authors.forename: Wen-feng
authors.initials: WF
authors.lastname: Zhang
authors.affiliation: Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guang dong Pharmaceutical University, Guang zhou, People's Republic of China.|School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guang zhou, People's Republic of China.
authors.forename: Hong-wei
authors.initials: HW
authors.lastname: Shao
authors.affiliation: Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guang dong Pharmaceutical University, Guang zhou, People's Republic of China.|School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guang zhou, People's Republic of China.
authors.forename: Feng-lin
authors.initials: FL
authors.lastname: Wu
authors.affiliation: Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guang dong Pharmaceutical University, Guang zhou, People's Republic of China.|School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guang zhou, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xie
authors.affiliation: Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guang dong Pharmaceutical University, Guang zhou, People's Republic of China.|School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guang zhou, People's Republic of China.
authors.forename: Zhu-ming
authors.initials: ZM
authors.lastname: Li
authors.affiliation: Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guang dong Pharmaceutical University, Guang zhou, People's Republic of China.|School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guang zhou, People's Republic of China.
authors.forename: Hua-ben
authors.initials: HB
authors.lastname: Bo
authors.affiliation: Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guang dong Pharmaceutical University, Guang zhou, People's Republic of China.|School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guang zhou, People's Republic of China.
authors.forename: Han
authors.initials: H
authors.lastname: Shen
authors.affiliation: Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guang dong Pharmaceutical University, Guang zhou, People's Republic of China.|School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guang zhou, People's Republic of China.
authors.forename: Teng
authors.initials: T
authors.lastname: Wang
authors.affiliation: Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guang dong Pharmaceutical University, Guang zhou, People's Republic of China.|School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guang zhou, People's Republic of China.
authors.forename: Shu-lin
authors.initials: SL
authors.lastname: Huang
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D036022:Capsid Proteins / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D011992:Endosomes / Q000648:ultrastructure / Q000821:virology; D036681:Fluorescence Recovery After Photobleaching; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D019169:Jurkat Cells; D008560:Membrane Fluidity; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D011956:Receptors, Cell Surface / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D013601:T-Lymphocytes / Q000378:metabolism* / Q000502:physiology; D022161:Transport Vesicles / Q000378:metabolism / Q000648:ultrastructure / Q000821:virology; D053586:Virus Internalization
chemical_list: D036022:Capsid Proteins; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins