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

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, IL1 alpha, LRF4, LFR7, TGF beta 1 and TLR4 in NAc, CCL2, CCL5, TGF beta 1 and TLR4 in PFC, and CASP3, CX3CR1, IFN alpha 1, IL1 beta and IL6 in VTA was significantly modulated in HIV-1Tg rats compared with F344 rats. IL1a 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.