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. 2021 Jun 4;223(11):1934-1942.
doi: 10.1093/infdis/jiaa657.

HIV-1 Transcription but Not Intact Provirus Levels are Associated With Systemic Inflammation

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HIV-1 Transcription but Not Intact Provirus Levels are Associated With Systemic Inflammation

Alex Olson et al. J Infect Dis. .

Abstract

Individuals infected with human immunodeficiency virus (HIV) 1 have increased inflammation, which has been associated with age-associated diseases. Plasma markers, cell-associated virus levels, and ability to stimulate RNA transcription in latently infected cell lines was examined in younger and older HIV-1-infected individuals with suppressed virus. Cell-associated RNA, but not intact provirus level, had positive correlation with plasma D-dimer levels. Compared with the younger group, the older group had higher D-dimer levels and a trend toward more cell-associated RNA but similar levels of intact proviruses. Even though all measured inflammatory markers were relatively higher in the older group, this greater inflammation did not induce more HIV-1 transcription in latently infected cell lines. Inflammation and HIV-1 RNA expression increase with age despite similar levels of intact infectious HIV DNA. While plasma inflammation is correlated with HIV-1 RNA expression in peripheral blood mononuclear cells, it does not induce HIV-1 transcription in latently infected cell lines.

Keywords: HIV-1 latency; accelerated aging; cell-associated HIV; inflammation; viral transcription.

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Figures

Figure 1.
Figure 1.
Correlation between virus measurements and plasma inflammatory markers. Association between intracellular human immunodeficiency virus type 1 (HIV-1) cell associated RNA (ca-RNA) and D-dimer (A) and between intact proviral DNA and soluble CD163 (sCD163) (B). Data from younger (gray circles) and older (black squares) participants are shown, along with ρ values, P values for Pearson correlation, and the number of data points. Black and dotted lines represent linear regression and 95% confidence interval, respectively. Abbreviation: PBMCs, peripheral blood mononuclear cells.
Figure 2.
Figure 2.
Older people with human immunodeficiency virus (PWH) have higher levels plasma inflammation than younger PWH, as shown by comparison of D-dimer (A), cell-associated RNA (ca-RNA) (B), and intact proviral DNA (C) between younger (gray circles) and older (black squares) groups. Black bars represent medians with interquartile range. †P < .001 (2-sided Student t test ). Numbers of individual data points are noted parenthetically. Abbreviation: PBMCs, peripheral blood mononuclear cells.
Figure 3.
Figure 3.
Tumor necrosis factor (TNF) α in the presence of plasma stimulates RNA transcription in latently infected cells. Levels of J-Lat (A) and ACH-2 (B) human immunodeficiency virus type 1 (HIV-1) RNA per HIV-1 DNA were measured in the presence or absence of 5-ng/mL TNF-α and plasma from younger (gray circles) or older (black squares) people with HIV. Black bars represent medians with interquartile range. *P < .05; †P < .001.

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