A Coat of Many Colors: Neuroimmune Crosstalk in Human Immunodeficiency Virus Infection

Abstract

The use of antiretroviral therapy (ART) has reduced mortality and increased the quality of life of HIV-1 infected people in more developed countries, where access to treatment is more widespread. However, morbidities continue which include HIV-1 associated neurocognitive disorders (HAND). Subtle cognitive abnormalities and low-level viral replication underlie disease. The balance between robust antiviral adaptive immunity, neuronal homeostatic mechanisms, and neuroprotective factors on one hand and toxicities afforded by dysregulated immune activities on the other govern disease. In the ART era, these lead to chronic low-level infection and often subclinical disease. New insights into the pathobiological processes for neuroimmune-linked disease and ways to modulate such activities for therapeutic gain are discussed. Better understanding the complexities of immune regulation during HAND can improve diagnosis and disease outcomes but is also relevant for the pathogenesis of a broad range of neurodegenerative disorders.

A lipid storage–like disorder contributes to cognitive decline in HIV-infected subjects

“…8,9 Despite cART, there is evidence for ongoing neurologic damage that includes persistent astrocyte infection, brain volume loss, inflammation, synaptodendritic damage, and disruptions in white matter integrity. 5,[10][11][12] The mechanisms underlying these residual neuropathologic impairments remain obscure.…”

“…8,9 Despite cART, there is evidence for ongoing neurologic damage that includes persistent astrocyte infection, brain volume loss, inflammation, synaptodendritic damage, and disruptions in white matter integrity. 5,[10][11][12] The mechanisms underlying these residual neuropathologic impairments remain obscure.Several studies have suggested that dysregulations in CNS lipid metabolism may be involved in the pathogenesis of HAND. [13][14][15] In particular, roles for ceramides, sphingomyelins, and cholesterol have been described, but the interrelationships of these bioactive lipids to the temporal progression *These authors contributed equally to this work.…”

Wingless-type Mammary Tumor Virus Integration Site Family, Member 5A (Wnt5a) Regulates Human Immunodeficiency Virus Type 1 (HIV-1) Envelope Glycoprotein 120 (gp120)-induced Expression of Pro-Inflammatory Cytokines via the Ca2+/Calmodulin-dependent Protein Kinase II (CaMKII) and c-Jun N-terminal Kinase (JNK) Signaling Pathways

“…The expression of pro-inflammatory cytokines, a molecular hallmark of chronic neuroinflammation, critically contributes to the pathogenesis of various HIV-associated neurological disorders (HANDs) (2)(3)(4). However, the mechanism that underlies the HIV-related cytokine expression in the CNS is still poorly understood.…”

Links between Progressive HIV-1 Infection of Humanized Mice and Viral Neuropathogenesis

“…24,25 Moreover, only the later stages of disease have been studied in detail where encephalitis is seen as a result of virus-infected MP and MP-derived multinucleated giant cells (MGC), astrogliosis, myelin pallor, and neuronal dropout predominate. 26,27 Little is known about the early stages of disease after acute infection. Here the pathobiological findings include aseptic meningitis.…”