Dataset Information

Modeling HIV-1 infection in the brain.

ABSTRACT: While highly active antiretroviral therapy (HAART) is successful in controlling the replication of Human Immunodeficiency Virus (HIV-1) in many patients, currently there is no cure for HIV-1, presumably due to the presence of reservoirs of the virus. One of the least studied viral reservoirs is the brain, which the virus enters by crossing the blood-brain barrier (BBB) via macrophages, which are considered as conduits between the blood and the brain. The presence of HIV-1 in the brain often leads to HIV associated neurocognitive disorders (HAND), such as encephalitis and early-onset dementia. In this study we develop a novel mathematical model that describes HIV-1 infection in the brain and in the plasma coupled via the BBB. The model predictions are consistent with data from macaques infected with a mixture of simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus (SHIV). Using our model, we estimate the rate of virus transport across the BBB as well as viral replication inside the brain, and we compute the basic reproduction number. We also carry out thorough sensitivity analysis to define the robustness of the model predictions on virus dynamics inside the brain. Our model provides useful insight into virus replication within the brain and suggests that the brain can be an important reservoir causing long-term viral persistence.

SUBMITTER: Barker CT

PROVIDER: S-EPMC7714358 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Modeling HIV-1 infection in the brain.

Barker Colin T CT Vaidya Naveen K NK

PLoS computational biology 20201119 11

While highly active antiretroviral therapy (HAART) is successful in controlling the replication of Human Immunodeficiency Virus (HIV-1) in many patients, currently there is no cure for HIV-1, presumably due to the presence of reservoirs of the virus. One of the least studied viral reservoirs is the brain, which the virus enters by crossing the blood-brain barrier (BBB) via macrophages, which are considered as conduits between the blood and the brain. The presence of HIV-1 in the brain often lead ...[more]

PMID: 33211686

Similar Datasets

Project description:BackgroundNumerous studies have used magnetic resonance spectroscopy (MRS) neurometabolite measurements to study HIV infection effects. While many have reported differences in total N-Acetylaspartate (tNAA), myo-Inositol (mI), and total Choline (tCho), there have been no meta-analyses performed to evaluate concordance across studies.PurposeTo evaluate the consistency of HIV serostatus effects on brain metabolites.Study selectionThe sample included studies conducted between 1993 and 2019 reporting HIV infection effects measured using proton MRS. tNAA/tCr ratios (21 papers), tCho/tCr ratios (21 papers), mI/tCr ratios (17 papers) and quantitative tCr (9 papers), sampling from basal ganglia (BG), gray matter (GM), and white matter (WM) were included.Data analysisRandom effects meta-analysis using inverse variance weighting and bias corrected standardized mean differences (SMDs) was used. Meta-regression examined effects of publication year and data acquisition technique differences.Data synthesisBG SMDs related to positive serostatus were -0.10 [-0.39; 0.18] tNAA/tCr, 0.27 [0.05; 0.49] tCho/tCr, 0.60 [0.31; 0.90] mI/tCr, and -0.26 [-0.59; 0.06] tCr. GM SMDs related to serostatus were -0.29 [-0.49; -0.09] tNAA/tCr, 0.37 [0.19; 0.54] tCho/tCr, 0.41 [0.15; 0.68] mI/tCr, and -0.24 [-0.45; -0.03] tCr. WM SMDs related to serostatus were -0.52 [-0.79; -0.25] tNAA/tCr, 0.41 [0.21; 0.61] tCho/tCr, 0.59 [0.24; 0.94] mI/tCr, and -0.03 [-0.25; 0.19] tCr. WM regions showed larger serostatus effect sizes than BG and GM. I2 ranged from 52 to 88% for the metabolite ratios. Both GM and WM tNAA/tCr SMDs were lower with increasing calendar year.LimitationsMany studies pooled participants with varying treatment, infection, and comorbidity durations.ConclusionsHIV neurometabolite studies showed consistently lower tNAA/tCr, higher tCho/tCr and higher mI/tCr ratios associated with chronic HIV infection. Substantial between-study variation may have resulted from measurement technique variations, study population differences and HIV treatment changes over time. Higher WM tCho/tCr and mI/tCr may reflect reactive gliosis or myelin turnover. Neurometabolite measurements can reliably detect chronic HIV infection effects and may be useful in understanding the pathophysiology of cognitive and sensorimotor decline following HIV infection.Classification of evidenceThis study provides Class II evidence of neurometabolite differences in chronic HIV infection.

Dataset Information

Modeling HIV-1 infection in the brain.

Publications

Modeling HIV-1 infection in the brain.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets