title: Inhibition of CXCR4 expression by recombinant adenoviruses containing anti-sense RNA resists HIV-1 infection on MT4 cell lines.
abstract: CXCR4-tropic (X4) variants are associated with faster disease progression than CCR5-tropic variants in HIV infection. We previously reported inhibition of CCR5 expression on U937 cells could protect the cells from HIV-1 infection. Here, we established recombinant adenoviruses containing anti-sense CXCR4 cDNA, to investigate its role in the protection of HIV entering into target cells. A fragment of 636 bp cDNA from CXCR4 mRNA was recombined into adenoviral vector and the recombinant adenovirus was obtained from AD-293 cells. The rates of CXCR4 expression on the MT4 cells infected with recombinant adenovirus were measured by FACS. The MT4 cells infected by recombinant adenovirus were challenged by T-tropic HIV-1 strains and then P24 antigen was assayed. The rate of expression of CXCR4 on MT4 cell infected with recombinant adenovirus was decreased from 42% to 1.12% at 24 h, and to 1.03%, 1.39%, and 1.23% at 48 h, 72 h and 10 days respectively. Compared with Ad-control cells, recombinant adenovirus infected MT4 cells produced much less P24 antigen after being challenged with HIV-1. Furthermore, the recombinant adenovirus had no effects on chemotactic activity and proliferation of the MT4 cells. In conclusion, recombinant adenoviruses containing anti-sense can inhibit CXCR4 expression and resist HIV-1 infection on MT4 cell lines.
authors.affiliation: Treatment & Research Center for Infectious Diseases, No. 302 Hospital of PLA, Beijing 100039, China No.100 Middle Road of the Western Fourth Round, Fengtai District, Beijing 100039, China.
authors.forename: Wen-Gang
authors.initials: WG
authors.lastname: Li
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Nie
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Chen
authors.forename: Tian-Jun
authors.initials: TJ
authors.lastname: Jiang
authors.forename: Xiao-Yuan
authors.initials: XY
authors.lastname: Xu
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D002460:Cell Line; D049109:Cell Proliferation; D002633:Chemotaxis / Q000276:immunology; D005786:Gene Expression Regulation; D005822:Genetic Vectors / Q000235:genetics*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D016372:RNA, Antisense / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D019718:Receptors, CXCR4 / Q000235:genetics*; D014161:Transduction, Genetic; D056189:Viral Tropism / Q000235:genetics
chemical_list: D016372:RNA, Antisense; D012333:RNA, Messenger; D019718:Receptors, CXCR4
keywords: AD-293 cells; C-C motif chemokine receptor type 5; C-X-C motif chemokine receptor type 4; CCR5; CXC chemokine receptor 4; CXCR4; FACS; HIV; HIV-1; Human kidney cells; MT4; MT4 cell lines; Recombinant adenoviruses; U937 cell; a T lymphocyte line; a lymphadenoma cell line; flow cytometry; human immunodeficiency virus