Defining the roles for Vpr in HIV-1-associated neuropathogenesis

James, Tony; Nonnemacher, Michael R.; Wigdahl, Brian; Krebs, Fred C.

doi:10.1007/s13365-016-0436-5

Cited by 18 publications

(14 citation statements)

References 86 publications

(158 reference statements)

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“…The HIV Vpr and Nef proteins also induce apoptosis in BMVECs, astrocytes, and neurons. In addition, Vpr exposure modulates ion channels and H 2 O 2 upregulation in neurons, impairs neuron maturation, and induces mitochondrial dysfunction in NPCs [ 17 , 33 ]. Exposure of Nef protein elevates proinflammatory factors (TNF-α, MIP-1, IL-6, etc.)…”

Section: Introductionmentioning

confidence: 99%

Common gene-network signature of different neurological disorders and their potential implications to neuroAIDS

et al. 2017

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The neurological complications of AIDS (neuroAIDS) during the infection of human immunodeficiency virus (HIV) are symptomized by non-specific, multifaceted neurological conditions and therefore, defining a specific diagnosis/treatment mechanism(s) for this neuro-complexity at the molecular level remains elusive. Using an in silico based integrated gene network analysis we discovered that HIV infection shares convergent gene networks with each of twelve neurological disorders selected in this study. Importantly, a common gene network was identified among HIV infection, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and age macular degeneration. An mRNA microarray analysis in HIV-infected monocytes showed significant changes in the expression of several genes of this in silico derived common pathway which suggests the possible physiological relevance of this gene-circuit in driving neuroAIDS condition. Further, this unique gene network was compared with another in silico derived novel, convergent gene network which is shared by seven major neurological disorders (Alzheimer’s disease, Parkinson’s disease, Multiple Sclerosis, Age Macular Degeneration, Amyotrophic Lateral Sclerosis, Vascular Dementia, and Restless Leg Syndrome). These networks differed in their gene circuits; however, in large, they involved innate immunity signaling pathways, which suggests commonalities in the immunological basis of different neuropathogenesis. The common gene circuits reported here can provide a prospective platform to understand how gene-circuits belonging to other neuro-disorders may be convoluted during real-time neuroAIDS condition and it may elucidate the underlying–and so far unknown–genetic overlap between HIV infection and neuroAIDS risk. Also, it may lead to a new paradigm in understanding disease progression, identifying biomarkers, and developing therapies.

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Section: Introductionmentioning

confidence: 99%

Common gene-network signature of different neurological disorders and their potential implications to neuroAIDS

et al. 2017

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“…Vpr is another HIV-1 accessory protein that has been implicated as a causative factor for the development of HAND [255,256]. Just as Tat is subject to mutation during replication and selection, the Vpr coding sequence may vary as HIV-1 infection progresses.…”

Section: Discussionmentioning

confidence: 99%

Genetic variation and function of the HIV-1 Tat protein

Spector

Mele

Wigdahl

et al. 2019

Med Microbiol Immunol

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Human immunodeficiency virus type 1 (HIV-1) encodes a transactivator of transcription (Tat) protein, which has several functions that promote viral replication, pathogenesis, and disease. Amino acid variation within Tat has been observed to alter the functional properties of Tat and, depending on the HIV-1 subtype, may produce Tat phenotypes differing from viruses representative of each subtype and commonly used in in vivo and in vitro experimentation. The molecular properties of Tat allow for distinctive functional activities to be determined such as the subcellular localization and other intra-and extracellular functional aspects of this important viral protein influenced by variation within the Tat sequence. Once Tat has been transported into the nucleus and becomes engaged in transactivation of the long terminal repeat (LTR), various Tat variants may differ in their capacity to activate viral transcription. Post-translational modification patterns based on these amino acid variations may alter interactions between Tat and host factors, which may positively or negatively affect this process. Additionally, the ability of HIV-1 to utilize or not utilize the transactivation response (TAR) element within the LTR, based on genetic variation and cellular phenotype, adds a layer of complexity to the processes that govern Tatmediated proviral DNA-driven transcription and replication. In contrast, cytoplasmic or extracellular localization of Tat may cause pathogenic effects in the form of altered cell activation, apoptosis, or neurotoxicity. Tat variants have been shown to differentially induce these processes, which may have implications for long-term HIV-1-infected patient care in the antiretroviral therapy era. Future studies concerning genetic variation of Tat with respect to function should focus on variants derived from HIV-1-infected individuals to efficiently guide Tat-targeted therapies and elucidate mechanisms of pathogenesis within the global patient population.

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“…Viral protein R (Vpr) is another accessory protein of HIV-1 and is important for the infection of cells of the monocytes-macrophages lineage and the nuclear localization of the pre-integration complex [137]. Using immunohistochemistry, Vpr has been detected in the basal ganglia and frontal cortices of patients with HIV encephalitis [138].…”

Section: Vprmentioning

confidence: 99%

Potential pharmacological approaches for the treatment of HIV-1 associated neurocognitive disorders

Omeragic

Kayode

Hoque

et al. 2020

Fluids Barriers CNS

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HIV associated neurocognitive disorders (HAND) are the spectrum of cognitive impairments present in patients infected with human immunodeficiency virus type 1 (HIV-1). The number of patients affected with HAND ranges from 30 to 50% of HIV infected individuals and although the development of combinational antiretroviral therapy (cART) has improved longevity, HAND continues to pose a significant clinical problem as the current standard of care does not alleviate or prevent HAND symptoms. At present, the pathological mechanisms contributing to HAND remain unclear, but evidence suggests that it stems from neuronal injury due to chronic release of neurotoxins, chemokines, viral proteins, and proinflammatory cytokines secreted by HIV-1 activated microglia, macrophages and astrocytes in the central nervous system (CNS). Furthermore, the blood-brain barrier (BBB) not only serves as a route for HIV-1 entry into the brain but also prevents cART therapy from reaching HIV-1 brain reservoirs, and therefore could play an important role in HAND. The goal of this review is to discuss the current data on the epidemiology, pathology and research models of HAND as well as address the potential pharmacological treatment approaches that are being investigated.

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Defining the roles for Vpr in HIV-1-associated neuropathogenesis

Cited by 18 publications

References 86 publications

Common gene-network signature of different neurological disorders and their potential implications to neuroAIDS

Common gene-network signature of different neurological disorders and their potential implications to neuroAIDS

Genetic variation and function of the HIV-1 Tat protein

Potential pharmacological approaches for the treatment of HIV-1 associated neurocognitive disorders

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