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Published on: January 5, 2016
Proviral load and immune function in blood and lymph node during HIV-1 and HIV-2 infection
O Jobe1, K Ariyoshi, A Marchant
1Medical Research Council Laboratories, Fajara, The Gambia. ojobe@mrc.gm
Insights
Human Immunodeficiency Virus (HIV) infection shows higher viral loads in lymph nodes than peripheral blood. This lymph node tropism in both HIV-1 and HIV-2 may increase tuberculosis susceptibility due to reduced immune responses.
Area of Science:
- Immunology
- Virology
- Infectious Diseases
Background:
- Human Immunodeficiency Virus (HIV) infection affects immune cells, with varying impacts depending on the viral subtype (HIV-1 vs. HIV-2).
- Lymphadenopathy is a common clinical manifestation in HIV infection, suggesting involvement of lymphoid tissues.
Purpose of the Study:
- To compare proviral load, lymphocyte phenotype, and function in peripheral blood and lymph node compartments in patients with HIV-1, HIV-2, and dual infections.
- To investigate the implications of compartmental viral distribution and immune cell function on disease progression and susceptibility to opportunistic infections like tuberculosis.
Main Methods:
- Analysis of peripheral blood mononuclear cells (PBMC) and lymph node mononuclear cells (LNMC) from 17 HIV-1, 12 HIV-2, and 3 dually infected patients.
- Quantification of proviral load and assessment of CD4+ cell percentages in both compartments.
- Evaluation of lymphocyte proliferation and interferon-gamma (IFN-gamma) production in response to purified protein derivative (PPD).
Main Results:
- CD4+ cell percentages were significantly higher in LNMC compared to PBMC for both HIV-1 and HIV-2 infections.
- Adjusted proviral load was higher in LNMC than PBMC for both HIV types, with strong correlations between compartments.
- Lymphocyte responses (proliferation and IFN-gamma production) to PPD were lower in LNMC and PBMC compared to healthy controls, indicating impaired immune function.
Conclusions:
- HIV-1 and HIV-2 infected cells exhibit tropism for lymph nodes, leading to a higher viral burden in this compartment.
- Lower lymphocyte responses to recall antigens in lymphoid tissues may contribute to increased susceptibility to opportunistic infections, such as tuberculosis, in HIV-infected individuals.
Abstract:
Proviral load as well as lymphocyte phenotype and function were compared in peripheral blood and lymph node compartments of 17 HIV-1, 12 HIV-2 and three dually infected patients with lymphadenopathy. The mean percentage (95% confidence interval (CI)) of CD4+ cells was higher in lymph node mononuclear cells (LNMC) than in peripheral blood mononuclear cells (PBMC) in both infections, being 26.7% (21. 1%, 32.3%) and 15.3% (10.4%, 20.2%), respectively, for HIV-1-infected patients (P = 0.0001) and 32.3% (22.7%, 41.9%) and 22. 1% (13.6%, 30.6%), respectively, for HIV-2-infected patients (P = 0. 02). In both types of infection, proviral load adjusted for number of CD4+ cells was higher in LNMC than in PBMC: the geometric mean (95% CI) was 8937 (4991; 16 003) and 4384 (2260; 8503), respectively, for HIV-1 patients (P = 0.02) and 1624 (382; 6898) and 551 (147; 2058) DNA copies, respectively, for HIV-2 patients (P = 0.05). Proviral load in both compartments was closely correlated (HIV-1, r = 0.60, P = 0.01; and HIV-2, r = 0.83, P = 0.0003). In both infections, proliferation and interferon-gamma (IFN-gamma) production in response to purified protein derivative (PPD) was lower in LNMC than in PBMC, both of which, in turn, were lower than in healthy controls. These results indicate that in HIV-2 as in HIV-1 infection, infected cells have a tropism for the lymph nodes resulting in higher viral load in this compartment and lower lymphocyte responses to the recall antigen PPD which may increase susceptibility to tuberculosis.
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