HIV-1 decreases the levels of neurotrophins in human lymphocytes

Abstract

Neurotrophins control cell survival. Therefore, we examined whether HIV-1 reduces neurotrophin levels. Serum of HIV-positive individuals exhibited lower concentrations of brain-derived neurotrophic factor (BDNF), but not of other neurotrophins, than HIV-negative individuals. In addition, R5 and X4 strains of HIV-1 decreased BDNF expression in T cells. Our results support the hypothesis that reduced levels of BDNF may be a risk factor for T-cell apoptosis and for neurological complications associated with HIV-1 infection.

Figure 1. HIV-1 and BDNF levels

A. The amount of BDNF was determined in the serum of HIV positive (n=109) and negative (n=54) individuals, non drug or drug abusers by ELISA according to the manufacturer’s instructions (Promega Corp.). The study was approved by Georgetown University Institutional Review Board. HIV and drug use status did not interact [F(1, 155) =0.076, p=0.783]. However, main effects of HIV status [F (1, 155) =5.203, p=0.024] and drug use [F (1, 155) =7.27, p=0.008] were observed. B. BDNF mRNA levels were determined by real-time quantitative polymerase chain reaction (RT-PCR) in the indicated cells obtained from peripheral blood peripheral blood mononuclear cells taken from healthy volunteers. Primers for BDNF were 5′-CATTGGCTGACACTTTCGA-3′ and 5′-ACTGAGCATCACCCTGGAC-3′ (forward, reverse). Hypoxanthine phosphoribosyltransferase 1 was used as a housekeeping gene. Data are the mean ± SEM of three independent samples. C. Human T cells (0.5 × 10⁶ cells/well) prepared as previously described [22] were infected for 2 hr with ~100 TCID₅₀ of HIV_BaL or HIV_IIIB. Infection was monitored by p24 ELISA (PerkinElmer Life Sciences, Inc.). BDNF mRNA levels were determined 24 hr after the infection by RT-PCR. Reverse-transcriptase negative controls were used to exclude genomic DNA contamination. Data, expressed as % of untreated cells, represent the mean of two independent preparations.