1573. HIV-1 Infection ?Alters the Expression Levels of Host Immunity and Aging Related Genes ?Associated with CD4+ T cell Activation
Session: Poster Abstract Session: Microbial and Host Genetic Factors in Disease
Saturday, October 5, 2013
Room: The Moscone Center: Poster Hall C
Posters
  • 1573_IDWPOSTER_update2.pdf (6.2 MB)
  • Background:   Even with successful treatment with HAART, activation levels remain above normal in HIV patients. In this study we analyzed the effect of HIV infection and CD4+ T cell activation on immunity related host gene (CD28, CD27, CD38, CCR7, HSP90, p21/WAF1) expression. Moreover, p21, CD27, and CD28 have also been identified as cellular aging markers  involved in telomere damage and replicative senescence. Confirmation of virus-associated changes in the expression of these genes contribute to HIV-1 induced immune activation will assist in the development of novel strategies for HIV treatment.

    Methods: CD4+ cells were purified from PBMCs from 49 subjects (33 HIV+ and 16 Healthy controls) by using anti-CD4 microbeads (Miltenyi Biotec). mRNA was isolated and reverse transcribed to cDNA by iScriptTMcDNA Synthesis Kit (Bio-Rad) and expression levels were evaluated by RT-PCR array (Applied Biosystems). β-actin and GAPDH were used as housekeeping genes to normalize gene expression results. Data analysis was performed with DataAssist v3.01 (Applied Biosystems). P-values were adjusted to control the false discovery rate using the Benjamini–Hochberg method. Activation is determined using relevant antibodies and flow cytometer (BD Biosciences).

    Results:  Compared to CD4+ cells from HIV uninfected controls, CD27, CD28, CCR7, and HSP90 were decreased by 1.75-fold, 1.53-fold, 1.82-fold, and 1.19-fold in CD4+ cells from HIV infected patients, respectively (p = 0.006, 0.002, 0.002, and 0.05). A higher expression level of p21/WAF1 (3.35 fold, p = 0.006) was observed in CD4+ T cells of HIV+ patients relative to healthy controls. Examiation of the relationship between CD4+ T-cell activation (% CD4+CD38+HLA-DR+) and the expression of these genes showed that CD4+ T cell activation was inversely associated with HSP90 (p = 0.034) and CD28 (p=0.04). A high percentage of non-activated CD4+ T cells were marginally associated with both genes.

    Conclusion:  Our finding demonstrates that HIV infection might alter immunity and aging related host cellular genes and contributes to 
immune activation. The genes studied in this work could potentially serve as novel drug targets or biomarkers of HIV disease progression.

    Chi-Lin Lee, Ph.D, Pediatrics, University of Southern California, Los Angeles, CA, Erik Serrao, Ph.D, Medicine, Harvard University, Boston, MA, Toni Frederick, PhD, Research Pediatrics, University of Southern California, Los Angeles, CA, Nouri Neamati, Ph.D, Pharmacology and Pharmaceutical Sciences, university of Southern California, Los Angeles, CA and Andrea Kovacs, MD, Pediatrics, Keck School of Medicine at USC, Los Angeles, CA

    Disclosures:

    C. L. Lee, None

    E. Serrao, None

    T. Frederick, None

    N. Neamati, None

    A. Kovacs, None

    Findings in the abstracts are embargoed until 12:01 a.m. PST, Oct. 2nd with the exception of research findings presented at the IDWeek press conferences.