Viral and cellular factors underlying neuropathogenesis in HIV associated neurocognitive disorders (HAND)

Abstract

As the HIV-1 epidemic enters its fourth decade, HIV-1 associated neurological disorders (HAND) continue to be a major concern in the infected population, despite the widespread use of anti-retroviral therapy. Advancing age and increased life expectancy of the HIV-1 infected population have been shown to increase the risk of cognitive dysfunction. Over the past 10 years, there has been a significant progress in our understanding of the mechanisms and the risk factors involved in the development of HAND. Key events that lead up to neuronal damage in HIV-1 infected individuals can be categorized based on the interaction of HIV-1 with the various cell types, including but not limited to macrophages, brain endothelial cells, microglia, astrocytes and the neurons. This review attempts to decipher these interactions, beginning with HIV-1 infection of macrophages and ultimately resulting in the release of neurotoxic viral and host products. These include: interaction with endothelial cells, resulting in the impairment of the blood brain barrier; interaction with the astrocytes, leading to metabolic and neurotransmitter imbalance; interactions with resident immune cells in the brain, leading to release of toxic cytokines and chemokines. We also review the mechanisms underlying neuronal damage caused by the factors mentioned above. We have attempted to bring together recent findings in these areas to help appreciate the viral and host factors that bring about neurological dysfunction. In addition, we review host factors and viral genotypic differences that affect phenotypic pathological outcomes, as well as recent advances in treatment options to specifically address the neurotoxic mechanisms in play.

Central and peripheral reservoirs of feline immunodeficiency virus in cats: a review

“…These findings point to some similarities in viral pathogenesis for the CNS shared by FIV and HIV-1 ( [74,105] -review with references therein). Indeed, based on multiple reports, the brain has proven to be an important target during early FIV infection and, similar to HIV, has been associated with various pathologic features such as encephalitis, microgial activation and, in some cases, degenerative changes like myelin pallor ( [74,105] and references therein; [104,106]). …”

New insights into immune reconstitution inflammatory syndrome of the central nervous system

“…While the term IRIS has been used to describe the more severe form of inflammation, and is thereby recognizable from clinical signs, it is becoming increasingly apparent that IRIS is a spectrum disorder and may range in severity and chronicity. All patients with HIV infection managed with ART undergo acute immune dysregulation and chronic inflammation and immune dysfunction (4, 5) that may contribute to HIV associated pathologies such as stroke (6), autoimmunity (7, 8), HIV-associated neurological disorders (HAND) (9, 10), cancer (11, 12) and premature aging (13-15). …”

Monocyte Traffic, Dorsal Root Ganglion Histopathology, and Loss of Intraepidermal Nerve Fiber Density in SIV Peripheral Neuropathy

“…20e22 Because HIV and SIV are unable to productively infect neurons, damage at the DRG is thought to be due to infected and activated macrophages and glial cells, which can secrete neurotoxic products. 23 Whether inflammation or recruited monocytes/macrophages play a role in damage has yet to be defined in an experimental SIV model. Factors involved in immune cell trafficking to the DRG during HIV/SIV infection are poorly understood.…”