Differential gene expression in CD8+ cells from HIV-1-infected subjects showing suppression of HIV replication

Abstract

CD8(+) cells from healthy HIV-1-infected individuals suppress human immunodeficiency virus (HIV) replication in infected cells by a non-cytotoxic mechanism. This activity is associated with the production of a soluble CD8(+) cell antiviral factor (CAF) that inhibits viral replication at the level of transcription. Strong CD8(+) cell non-cytotoxic anti-HIV responses (CNARs) correlate with an asymptomatic state and long-term survival of HIV-infected individuals. This antiviral activity is lost when the infected individual advances to disease. In attempts to define the gene(s) mediating CNAR we have evaluated differential gene expression between CD8(+) cells from infected subjects with high CNAR and CD8(+) cells from uninfected controls that lack this activity. The expression analysis, using the Affymetrix GeneChip Human Genome U133 Set, indicated that 18% of the genes were differentially expressed (DE) of which 9.2% were up-regulated. A total of 568 genes were up-regulated with a >2.0-fold difference in expression levels and a >50% concordance of difference call. Stringent selection criteria narrowed down the list to 52 up-regulated 'high confidence genes' (> or = 75% concordance). These genes function in a wide variety of cellular processes and include 13 associated with immunologic activity.

Pre-infection transcript levels of FAM26F in peripheral blood mononuclear cells inform about overall plasma viral load in acute and post-acute phase after simian immunodeficiency virus infection

“…Uninfected macaques were included to minimize the effects that might potentially be related to long-term SIV-infection and distinguishes this work from previously published experiments in HIV-infected humans (Diaz et al , 2003; Katz et al , 2011; Killian et al , 2013; Martinez-Mariño et al , 2007). Comparison between CNAR(−) versus CNAR(+) animals revealed 143 differentially regulated genes (differential expression over twofold, P <0.1), which belonged to diverse biological processes (Table S1, Fig.…”

“…The first study involved a pair of HIV-1 discordant identical twins (Diaz et al , 2003). Another study included four CNAR-positive and four CNAR-negative HIV-infected individuals (Martinez-Mariño et al , 2007). There was no overlap between the genes identified in these two reports.…”

Transcriptional and Posttranscriptional Regulation of Cytokine Gene Expression in HIV-1 Antigen-Specific CD8+T Cells That Mediate Virus Inhibition

“…In order to identify correlates of antiviral control, we assessed the expression of a panel of cytokines, including MIP-1␣, MIP-1␣P, MIP-1␤, IFN-␥, XCL1, GM-CSF, RANTES, and TNFRSF9. We and others have shown that IFN-␥ and the ␤-chemokines MIP-1␣ and MIP-1␤ are associated with CD8 ϩ T cell inhibition of HIV-1 (17,42,(44)(45)(46)(47)(48). MIP-1␣, MIP-1␣P, and MIP-1␤ bind CCR5 and block the entry of R5-tropic viruses (including transmitted/founder viruses) in CD4 ϩ T cells (44,49,50).…”

Discovery of another anti-HIV protein in the search for the CD8+ cell anti-HIV Factor

“…The antiviral activity of this nuclear protein had been suggested by earlier restriction differentiation analyses studies indicating that TOE1 RNA was expressed at higher levels in cells showing CNAR vs. those that did not (21). This finding, however, was not confirmed by subsequent DNA microarray procedures (22,23). The de Belle research group based their conclusion on TOE1 and CAF from the effect of TOE1 on HIV transcription, its surprising secretion by CD8+ lymphocytes, and its ability to penetrate cells and block HIV replication (17).…”