Book chapter
Chapter 12 - Role of extracellular viral regulatory proteins in neuropathogenesis
HIV-Associated Neurocognitive Disorders, pp 179-207
2024
Abstract
Throughout the human immunodeficiency virus (HIV) epidemic, neuropathogenic properties of the virus have become an important aspect of the disease process. In the early years, this was thought to be in large part due to the central nervous system (CNS) viral load. As combination antiretroviral therapy (ART) became more effective and viral load in the CNS was decreased, the severity of neurocognitive impairment decreased but it did not decrease the percentage of individuals with this neurologic comorbidity. Infection in the CNS occurs in the acute stage of infection with the establishment of a CNS viral reservoir. Viruses within this reservoir are thought to evolve in a compartmentalized manner, making the variants and potential pathogenesis of the viruses in the CNS unique to that compartment. Currently, neurocognitive impairment is thought to be the result of smoldering chronic viral infection where the viral load is kept low or undetectable with viral proteins produced over long periods of time resulting in disruption of intracellular dysfunction and deregulation of intercellular communication pathways. This cellular dysfunction is both in the infected cell populations and within the uninfected cell populations as intra- versus extracellular proteins, respectively. Infected cells include the perivascular macrophage, microglia, and astrocyte and cells of the blood–brain barrier, whereas the uninfected cells include those four cell populations as well as neurons. The combination of effects between these cells results in dysregulation of cytokines, chemokines, ROS, glutamate balance, etc. The HIV proteins shown to individually and likely in combination cause neurotoxicity are Tat, Vpr, Nef, and gp120. With the exception of gp120, these are all viral regulatory proteins. As such, this chapter will focus on the role of these viral proteins in neuropathogenic process following viral CNS invasion.
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Details
- Title
- Chapter 12 - Role of extracellular viral regulatory proteins in neuropathogenesis
- Creators
- Michael R. Nonnemacher - Drexel UniversityRachel E. Berman - Drexel UniversityJill M. Lawrence - Drexel UniversityMackenzie E. Collins - Drexel UniversityTheodore E. Gurrola - Drexel UniversityWill Dampier - Drexel UniversityBrian Wigdahl - Drexel University
- Publication Details
- HIV-Associated Neurocognitive Disorders, pp 179-207
- Publisher
- Elsevier
- Resource Type
- Book chapter
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Scopus ID
- 2-s2.0-85189575595
- Other Identifier
- 991022074080904721