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Modulation Effect of HIV-1 Viral Proteins and Nicotine on Expression of the Immune-Related Genes in Brain of the HIV-1 Transgenic Rats

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Abstract

The human immunodeficiency virus-1 transgenic (HIV-1Tg) rat is a non-infectious rodent model for HIV-1 infection which develops altered immune-responses similar to those in persons infected with HIV-1. HIV-1Tg and F344 rats respond significantly different to morphine, ethanol, nicotine and other psychostimulants, although the molecular mechanisms underlying these differences remain largely undetermined. Here, we compared expression of 52 immune-related genes in the prefrontal cortex (PFC), nucleus accumbens (NAc), and ventral tegmental area (VTA) of HIV-1Tg and F344 rats treated with either nicotine (0.4 mg/kg nicotine, base, s.c.) or saline for 27 days, to identify differentially expressed genes in the presence of HIV-1 with and without nicotine treatment. Using quantitative RT-PCR array, we measured RNA expression levels. Results showed that RNA expression of CASP3, CCL5, CX3CL1, CX3CR1, IL1α, LRF4, LFR7, TGFβ1 and TLR4 in NAc, CCL2, CCL5, TGFβ1 and TLR4 in PFC, and CASP3, CX3CR1, IFNα1, IL1β and IL6 in VTA was significantly modulated in HIV-1Tg rats compared with F344 rats. IL1α showed a 58 % (P = 0.000072) decrease and IRF6 showed a 93.7 % increase (P = 0.000227) in the NAc of HIV-1Tg compared with F344 rats; results remained significant after correction for multiple testing. We also found that several genes were significantly modulated by nicotine in HIV-1Tg rats while only a small number of immune-related genes were altered by nicotine in F344 rats. These findings imply that HIV-1 viral proteins greatly impact immune function and alter responsiveness to nicotine in certain immune-related genes.

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Acknowledgments

The authors thank Drs. Shaolin Wang, Junran Cao, and Guohua Song for their assistance with sample collection during the experiments. This work was supported, in part, by US National Institutes of Health grants DA-016149 to SLC and DA-026356 to SLC and MDL.

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Authors and Affiliations

  1. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

    Zhongli Yang & Ming D. Li

  2. Institute of NeuroImmune Pharmacology, Seton Hall University, South Orange, NJ, USA

    Zhongli Yang, Kaitlyn P. Connaghan & Sulie L. Chang

  3. Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA, USA

    Tanseli Nesil & Ming D. Li

  4. Department of Biological Sciences, Seton Hall University, South Orange, NJ, USA

    Sulie L. Chang

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  1. Zhongli Yang
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Correspondence to Sulie L. Chang.

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Yang, Z., Nesil, T., Connaghan, K.P. et al. Modulation Effect of HIV-1 Viral Proteins and Nicotine on Expression of the Immune-Related Genes in Brain of the HIV-1 Transgenic Rats. J Neuroimmune Pharmacol 11, 562–571 (2016). https://doi.org/10.1007/s11481-016-9679-4

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  • DOI: https://doi.org/10.1007/s11481-016-9679-4

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