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HIV-infection resistance in PMBC-derived dendritic cells modified with recombinant virus

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Abstract

This study aimed to identify the characteristics of recombinant-adenovirus-modified PBMC-derived dendritic cells and their resistance to HIV-1 infection by integrating the CCR5∆32, CCR5siRNA, HIV-1 pol and HIV-1 int genes into a recombinant adenovirus vector using the AdEasy system. Dendritic cells (DCs) were isolated from human PBMCs from blood of healthy donors. The expression of CCR5∆32, CCR5, CXCR4 and HIV-1 p24 in PBMCs or modified cells was measured by western blot, p24 expression in cell lysates was measured by ELISA, and HIV-1 entry was measured by β-galactosidase assay. Furthermore, T-cell immunity induced by the recombinant adenovirus was measured by ELISPOT assay. After the cells were modified by Ad-R5∆32siRNA, the expression of CCR5∆32 increased, while the expression of CCR5 and CXCR4 decreased. There was no adverse effect of adenoviral gene transfer on DC development. CD83 expression on the surface of mature DCs did not change after gene transfer. The expression of p24 remained at low levels in modified cells when challenged by HIV-1. The modified cells showed resistance to HIV-1 infection. Results indicated that recombinant-adenovirus-modified cells demonstrated good resistance to HIV-1 infection. Modification of HSC-derived immune cells, such as DCs, may be a potent strategy to resist HIV-1 infection.

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Acknowledgment

This work was supported by the Guangdong Family Planning and Reproductive Health Funding (20110266) to Xia. C, the Major International (Regional) Joint Research Project (2010DFA32660) and the Guangdong Natural Science Fund (10251008002000002, 10151008002000003) to Zhu P. The authors acknowledge and express appreciation to Carol Gordon, Fran Kovach and Michael Kwan for editing the manuscript.

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Authors and Affiliations

  1. Department of Pharmacy, The Third Affiliated Hospital, Medical University of Guangzhou, Guangzhou, 510150, China

    Cheng-lai Xia, Zheng-rong Mei, Hanhui Huang & Peng-ke Yan

  2. Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China

    Ping Zhu

  3. Department of Dermatology and Rheumatology, Foshan Maternity and Child Health Care Hospital, Foshan, 528000, China

    Yan-tao Cai

  4. Department of Radiology, The First Affiliated Hospital, Medical University of Guangzhou, Guangzhou, 515120, China

    Guang-bin Zhu

  5. Institute of Traditional Medicine of University of South China, Chenzhou No.1 People’s Hospital, Chenzhou, 423000, Hunan, China

    Di-xian Luo

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  1. Cheng-lai Xia
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Correspondence to Di-xian Luo or Peng-ke Yan.

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C. Xia, P. Zhu and Y. Cai contributed equally for this work.

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Xia, Cl., Zhu, P., Cai, Yt. et al. HIV-infection resistance in PMBC-derived dendritic cells modified with recombinant virus. Arch Virol 157, 413–421 (2012). https://doi.org/10.1007/s00705-011-1185-7

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  • DOI: https://doi.org/10.1007/s00705-011-1185-7

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