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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.
AuthorsWen-Gang Li, Wei-Min Nie, Wei-Wei Chen, Tian-Jun Jiang, Xiao-Yuan Xu, Min Zhao
JournalGene (Gene) Vol. 526 Issue 2 Pg. 443-8 (Sep 10 2013) ISSN: 1879-0038 [Electronic] Netherlands
PMID23510780 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2013 Elsevier B.V. All rights reserved.
Chemical References
  • RNA, Antisense
  • RNA, Messenger
  • Receptors, CXCR4
Topics
  • Adenoviridae (genetics)
  • Cell Line
  • Cell Proliferation
  • Chemotaxis (immunology)
  • Gene Expression Regulation
  • Genetic Vectors (genetics)
  • HIV-1 (physiology)
  • Humans
  • Lymphocytes (immunology, metabolism, virology)
  • RNA, Antisense (genetics)
  • RNA, Messenger (genetics)
  • Receptors, CXCR4 (genetics)
  • Transduction, Genetic
  • Viral Tropism (genetics)

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