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Changes in the level of apoptosis-related proteins in Jurkat cells infected with HIV-1 versus HIV-2

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Abstract

Human immunodeficiency virus (HIV) infection-induced apoptosis of infected CD4 T cells as well as uninfected (bystander) CD4 T cells and other types of cells is a major factor in the pathogenesis of AIDS. Clinically, HIV-2 patients have a higher CD4 cell count at the time of an AIDS diagnosis, and generally have longer survival after development of symptoms. The mortality after an AIDS diagnosis has been reported to be more influenced by CD4 cell count than HIV type. Previous studies have shown significant variations in cytopathic effects following in vitro infection with primary isolates of HIV-1 or HIV-2 subtypes; however, the relative contributions of HIV-1 and HIV-2 infection leading to cell death remain unclear. Using a human cell line, Jurkat, we examined differences in key molecules involved in apoptotic signaling pathways during infection with either HIV-1 or HIV-2. HIV-1 infection generated more reactive oxygen species (ROS), increased the expression of a larger number of molecules involved in cell signaling such as p47, p38α, JNK, c-Yes, total PKC, and decreased the expression of molecules such as p38β, ERK1/2, and XIAP relative to HIV-2 infection. HIV-1 induced a higher degree of cell death through stronger activation of both apoptotic pathways. HIV-1 infection downregulated both Bcl-XL and FLIP expressions at later time points postinfection, while HIV-2 infection dramatically upregulated both Bcl-XL and FLIP expression. We also found that the expression of Bcl-XL or FLIP resulted in significant inhibition of HIV replication in Jurkat cells. These findings suggest that HIV-1 infection with high levels of cytotoxicity results in a higher level of cell death through apoptosis during a short time postinfection. The longer period of infection observed with HIV-2 with a lower degree of cytotoxicity was accompanied by increased Bcl-XL and FLIP expression. High protein levels of Bcl-XL or FLIP inhibit HIV replication and may be one explanation for the clinical observation that HIV-2 infected patients generally tend to be long-term nonprogressors with high CD4 lymphocyte counts compared with HIV-1 infected persons.

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Acknowledgments

We thank Dr. Mingjie Zhang, Dr. Krishna Devadas, and Dr. Hira Nakhasi for critical review of this article. The findings and conclusions in this article have not been formally disseminated by the FDA and should not be construed to represent any Agency determination or policy.

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Authors and Affiliations

  1. Labaratory of Molecular Virology, Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, 20892, USA

    Xue Wang, Ragupathy Viswanath, Jiangqin Zhao, Shixing Tang & Indira Hewlett

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  1. Xue Wang
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  2. Ragupathy Viswanath
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  3. Jiangqin Zhao
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  4. Shixing Tang
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  5. Indira Hewlett
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Correspondence to Xue Wang or Indira Hewlett.

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Wang, X., Viswanath, R., Zhao, J. et al. Changes in the level of apoptosis-related proteins in Jurkat cells infected with HIV-1 versus HIV-2. Mol Cell Biochem 337, 175–183 (2010). https://doi.org/10.1007/s11010-009-0297-9

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  • DOI: https://doi.org/10.1007/s11010-009-0297-9

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