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

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Title:Characterization of HIV-1 binding to peripheral blood mononuclear cells versus monocytes/macrophages : relationship to neuropathogenesis
Authors:Munsaka, Sody
Keywords:HIV (Viruses) -- Pathogenesis
Date Issued:2007
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.
Description:Thesis (M.S.)--University of Hawaii at Manoa, 2007.
Includes bibliographical references (leaves 57-63).
xii, 63 leaves, bound col. ill. 29 cm
Rights:All UHM dissertations and theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission from the copyright owner.
Appears in Collections: M.S. - Biomedical Sciences (Tropical Medicine)

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