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A Rat Model of EcoHIV Brain Infection
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Modeling HIV-1 infection in the brain.

Colin T Barker1,2, Naveen K Vaidya3,4,5

  • 1Department of Mathematics and Computer Science, Drury University, Missouri, USA.

Plos Computational Biology
|November 19, 2020
PubMed
Summary

Human Immunodeficiency Virus (HIV-1) can persist in the brain, a viral reservoir, despite treatment. This study models HIV-1 brain infection dynamics, revealing insights into viral persistence and transport across the blood-brain barrier (BBB).

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Area of Science:

  • Virology
  • Neuroscience
  • Mathematical Biology

Background:

  • Highly Active Antiretroviral Therapy (HAART) controls Human Immunodeficiency Virus type 1 (HIV-1) but cannot eliminate viral reservoirs.
  • The brain is a poorly understood HIV-1 reservoir, with virus entry facilitated by macrophages crossing the blood-brain barrier (BBB).
  • HIV-1 infection in the brain can cause HIV-Associated Neurocognitive Disorders (HAND), including encephalitis and dementia.

Purpose of the Study:

  • To develop a novel mathematical model of HIV-1 infection dynamics in the brain and plasma, coupled via the BBB.
  • To estimate viral transport rates across the BBB and viral replication rates within the brain.
  • To analyze the sensitivity and robustness of the model's predictions regarding brain viral dynamics.

Main Methods:

  • Development of a novel mathematical model simulating HIV-1 infection in the brain and plasma.
  • Coupling of brain and plasma compartments via a representation of the blood-brain barrier (BBB).
  • Model validation using data from macaques infected with Simian Immunodeficiency Virus (SIV) and Simian-Human Immunodeficiency Virus (SHIV).

Main Results:

  • Model predictions align with experimental data from SIV/SHIV-infected macaques.
  • Estimation of the rate of virus transport across the BBB and viral replication within the brain.
  • Calculation of the basic reproduction number for HIV-1 in the brain.

Conclusions:

  • The mathematical model provides valuable insights into HIV-1 replication and dynamics within the brain.
  • The brain is identified as a significant viral reservoir contributing to long-term HIV-1 persistence.
  • Understanding brain viral dynamics is crucial for developing strategies to eradicate HIV-1 reservoirs.