Characterization of HIV-1 binding to peripheral blood mononuclear cells versus monocytes/macrophages: relationship to neuropathogenesis

Abstract

Individuals with HIV-1-associated dementia (HAD) are characterized with increased percentages of circulating activated monocytes/macrophages (M/MΦ) with CDl4/CDl6 phenotype. Higher levels of HIV-1 DNA are detected in these activated cells, thus hypothesizing that the activated M/MΦ have higher viral binding and possibly leading to more permissive infectivity. From a non-HIV-I-infected volunteer, peripheral blood mononuclear cells (PBMCs), magnetic bead-separated activated and non-activated monocytes were exposed to 2ng p24 units of LAI (X4 Strain) and p89.6 (dual tropic but preferentially X5 strain) for one hour at 37°C, 5% CO2. Viral binding capacity was assayed by RT-PCR using HIV Gag and β-actin primers with appropriate positive and negative control RNA and densitometry. Differences in binding capacities between each of the two groups were considered significant by Student's t-test and One-Way ANOVA if p<0.05. As expected, M/MΦ displayed a higher HIV-1 binding to p89.6 than to LAI, 0.497 vs. 0.328 (p=0.025), respectively. In the PBMCs, viral binding capacity was increased compared to M/MΦ , for LAI: 0.492 vs. 0.328, respectively (p=0.011); for p89.6: 0.878 vs. 0.497, respectively (p=0.004). Of note was the significantly higher binding found with p89.6 (0.878) compared to LAI (0.492) (p=0.004), since the PBMCs were from the same volunteer obtained at the same time. There was a trend for HIV-1 binding to be higher for activated monocytes [LAI (0.324), P89.6 (0.277)] compared to non-activated monocytes [LAI (0.22S), p89.6 (0.249)], p= 0.362. These results demonstrate that peripheral M/MΦ preferentially bind CCRS virus suggesting that the high HIV DNA found in PBMCs represents bound virus on the M/MΦ subset. The enhanced binding of CCR5 strains to M/MΦ , particularly to activated M/MΦ , may lead to more permissive infection of this subset. The theory that increased trafficking of HIV-1-infected activated M/MΦ to the central nervous system is consistent with the findings.