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Home arrow Environment arrow Inflammatory Disorders of the Nervous System: Pathogenesis, Immunology, and Clinical Management
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Etiology of Neurologic Manifestations in HIV

HIV-1 is a lentivirus (a subgroup of retrovirus) retrovirus and contains ribonucleic acid (RNA). Two distinct types are HIV-1 and HIV-2, while HIV-1 is the predominant virus worldwide. HIV strains can be macrophage - or T lymphocyte - tropic and are capable of infecting differentiated cells and macrophages. HIV infection of the brain involves various cells including perivascular macrophages/microglial cells and astrocytes (Table 3.4). HIV invasion and entry to the CNS is associated with neuroinvasion, neurotropism, and neurovirulence. As mentioned before, neuroinvasion most likely occurs early via infected macrophages which cross the BBB and

Table 3.4 Cells in human body which significantly affected by HIV/AIDS

Lymphoreticular system

CD4+ T lymphocyte

Macrophage

Monocyte

B lymphocyte

Endothelial cells

Microglia

Astrocytes

Oligodendrocytes

Neurons

infect adjacent cells. Another mode of entry via the choroid plexus has also been postulated. Infected macrophages/microglia and astrocytes generate and secrete a number of neurotoxic substances, which collectively add to the pathophysiology of HAD. Some of these are inflammatory cytokines such as TNF-a, IFN-Y, and platelet-activating factor. Levels of cytokines IL-1, IL-6, and TGF-p are elevated in the brain and CSF of patients with HAD. Chemokines are also released by activated and infected macrophages which include MIP-1a/CCL3, MIP-1p/CCL4, RANTES/ CCL5, SDF-1/CXCL12, and CX3CCL1. Other released inflammatory mediators include eicosanoids, excitatory amino acids (such as glutamate), reactive oxygen and nitrogen species, TNF-related apoptosis-inducing ligand, and viral proteins (gp120, gp41, Tat, Nef, and Vpr) (Fig. 3.1) [22].

HIV-infected macrophages and microglial cells release neurotoxic viral proteins that trigger astrocyte activation, which results in increased glutamate release and reduced glutamate uptake

Fig. 3.1 HIV-infected macrophages and microglial cells release neurotoxic viral proteins that trigger astrocyte activation, which results in increased glutamate release and reduced glutamate uptake. Elevated extracellular glutamate levels cause neuronal bioenergetic disturbances that lead to aberrant synaptodendritic pruning and neuronal injury. Moreover, systemic inflammation and microbial translocation products lead to microglial activation and increased production of chemo- kines and cytokines that contribute to neuronal injury (From Saylor et al. [22]. Copyright permission obtained; Adapted from Williams et al. [89])

Viral load found in CSF may be related to the severity of HAD. Increased levels of viral protein and RNA detected in CSF have been noted in HAD compared to non-demented AIDS patients.

 
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