Editorial NeuroAIDS review

Shapshak, Paul; Kangueane, Pandjassarame; Fujimura, Robert K.; Commins, Deborah; Chiappelli, Francesco; Singer, Elyse J.; Levine, Andrew J.; Minagar, Alireza; Novembre, Francis J.; Somboonwit, Charurut; Nath, Avindra; Sinnott, John T.

doi:10.1097/qad.0b013e328340fd42

Cited by 80 publications

(68 citation statements)

References 172 publications

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“…Infected cells within the brain release cytokines, chemokines, and neurotoxic viral proteins, including tat and gp120, which activate surrounding cells [62]. Activated microglia, macrophages, and astrocytes also produce inflammatory mediators including TNF-α, IL-1β, and IL-6 and the chemokines CCL2 and CXCL12, that recruit additional CD14 + CD16 + monocytes into the CNS contributing to neuroinflammation [63]. The infected and activated CNS cells elaborate neurotoxic host factors including arachidonic acid, quinolinic acid, and nitric oxide[62].…”

Section: Introductionmentioning

confidence: 99%

Monocytes Mediate HIV Neuropathogenesis: Mechanisms that Contribute to HIV Associated Neurocognitive Disorders

Williams¹,

Veenstra²,

Gaskill³

et al. 2014

CHR

132

129

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HIV infected people are living longer due to the success of combined antiretroviral therapy (cART). However, greater than 40-70% of HIV infected individuals develop HIV associated neurocognitive disorders (HAND) that continues to be a major public health issue. While cART reduces peripheral virus, it does not limit the low level, chronic neuroinflammation that is ongoing during the neuropathogenesis of HIV. Monocyte transmigration across the blood brain barrier (BBB), specifically that of the mature CD14+CD16+ population that is highly susceptible to HIV infection, is critical to the establishment of HAND as these cells bring virus into the brain and mediate the neuroinflammation that persists, even if at low levels, despite antiretroviral therapy. CD14+CD16+ monocytes preferentially migrate into the CNS early during peripheral HIV infection in response to chemotactic signals, including those from CCL2 and CXCL12. Once within the brain, monocytes differentiate into macrophages and elaborate inflammatory mediators. Monocytes/macrophages constitute a viral reservoir within the CNS and these latently infected cells may perpetuate the neuropathogenesis of HIV. This review will discuss mechanisms that mediate transmigration of CD14+CD16+ monocytes across the BBB in the context of HIV infection, the contribution of these cells to the neuropathogenesis of HIV, and potential monocyte/macrophage biomarkers to identify HAND and monitor its progression.

show abstract

Section: Introductionmentioning

confidence: 99%

Monocytes Mediate HIV Neuropathogenesis: Mechanisms that Contribute to HIV Associated Neurocognitive Disorders

Williams¹,

Veenstra²,

Gaskill³

et al. 2014

CHR

132

129

View full text Add to dashboard Cite

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“…HIV neuroinvasion in vivo occurs within the first month [61], and this early compartmentalization suggests a CNS reservoir for local virus production [62]. The neurodegenerative disease (neuroAIDS) progresses during chronic infection, with neurocognitive, behavioral, and motor impairments that can lead to full-blown HIV-associated dementia [58]. The mechanisms by which HIV causes neurodegeneration are not fully elucidated, and include both host and viral mechanisms [28,63].…”

Section: Msrv/herv-w/syncytin-1 Endogenous Retroviruses and Hiv-relatmentioning

confidence: 99%

“…The central nervous system (CNS) is a major target for the human immunodeficiency virus (HIV) [58][59][60]. HIV neuroinvasion in vivo occurs within the first month [61], and this early compartmentalization suggests a CNS reservoir for local virus production [62].…”

Section: Msrv/herv-w/syncytin-1 Endogenous Retroviruses and Hiv-relatmentioning

confidence: 99%

The aliens inside human DNA: HERV-W/MSRV/syncytin-1 endogenous retroviruses and neurodegeneration

Dolei

Uleri

Ibba

et al. 2015

J Infect Dev Ctries

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The human genome contains remnants of ancestral retroviruses now endogenously transmitted, called human endogenous retroviruses (HERVs). HERVs can be variably expressed, and both beneficial and detrimental effects have described. This review focuses on the MSRV and syncytin-1 HERV-W elements in relationship to neurodegeneration in view of their neuro-pathogenic and immune-pathogenic properties. Multiple sclerosis (MS) and a neurodegenerative disease (neuroAIDS) are reported in this review. In vivo studies in patients and controls for molecular epidemiology and follow-up studies are reviewed, along with in vitro cellular studies of the effects of treatments and of molecular mechanisms. HERV-W/MSRV has been repeatedly found in MS patients (in blood, spinal fluid, and brain samples), and MRSV presence/load strikingly parallels MS stages and active/remission phases, as well as therapy outcome. The DNA of MS patients has increased MSRVenv copies, while syncytin-1 copies are unchanged in controls. Presence of MSRV in the spinal fluid predicted the worst MS progression, ten years in advance. The Epstein-Barr virus (EBV) activates HERV-W/MSRV both in vitro and in vivo. With respect to neuroAIDS, the HIV transactivator of transcription (Tat) protein activates HERV-W/MSRV in monocytes/macrophages and astrocytes indirectly by interaction with TLR4 and induction of TNF. HERV-W/MSRV can be considered a biomarker for MS behavior and therapy outcome. Regarding MS pathogenesis, we postulate the possibility for EBV of an initial trigger of future MS, years later, and for MSRV of a direct role of effector of neuropathogenesis during MS. Additionally, HERV-W/MSR/syncytin-1 activation by HIV Tat could contribute to the HIV-related neurodegeneration.

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“…It covers a wide variety of disorders ranging from asymptomatic neurocognitive impairment (ANI), HIV-associated mild neurocognitive disorder (MND) to the most severe, HIV-associated dementia (HAD). 1 New evidence is emerging to the extent of HAND, with incidences ranging from 29% to 69% in the HIV positive population. 2 Several associations in the development of HAND have been described in the literature; viral-related factors, such as clade, uncontrolled viraemia and a high CNS viral load (compared to plasma), 3 immunerelated factors (current and nadir CD4 counts), and co-infection with hepatitis C. 4 HIV-associated dementia (HAD) is the most severe form of HAND.…”

Section: Directly Hiv-related (Table 3)mentioning

confidence: 99%