HIV-1 Infection of Neurons Might Account for Progressive HIV-1-Associated Encephalopathy in Children

Cantó-Nogués, Carmen; Sánchez-Ramón, Silvia; Álvarez, Susana; Lacruz, César R.; Ma, Mai‐Juan

doi:10.1385/jmn:27:1:079

Cited by 38 publications

(25 citation statements)

References 37 publications

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“…Once in the brain, HIV has been clearly shown to infect astrocytes and microglia [116-118]. In addition, and although controversial, there is also some evidence that HIV can also directly infect neurons [119-121]. No matter where the infection, the presence of the virus has been shown to induce a cytokine “storm” [122, 123].…”

Section: Influenza Virusmentioning

confidence: 99%

Viral parkinsonism

Jang

Boltz

Webster

et al. 2009

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

273

280

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Parkinson's disease is a debilitating neurological disorder characterized that affects 1-2% of the adult population over 55 years of age. For the vast majority of cases, the etiology of this disorder is unknown, although it is generally accepted that there is a genetic susceptibility to any number of environmental agents. One such agent may be viruses. It has been shown that numerous viruses can enter the nervous system, i.e. they are neurotropic, and induce a number of encephalopathies. One of the secondary consequences of these encephalopathies can be parkinsonism, that is both transient as well as permanent. One of the most highlighted and controversial cases of viral parkinsonism is that which followed the 1918 influenza outbreak and the subsequent induction of von Economo's encephalopathy. In this review, we discuss the neurological sequelae of infection by influenza virus as well as that of other viruses known to induce parkinsonism including Coxsackie, Japanese encephalitis B, St. Louis, West Nile and HIV viruses.

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Section: Influenza Virusmentioning

confidence: 99%

Viral parkinsonism

Jang

Boltz

Webster

et al. 2009

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

273

280

View full text Add to dashboard Cite

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“…However, there are reports indicating the presence of HIV-1 nucleic acids in neurons obtained from some AIDS patients. 16, 17 In addition, HIV-1 was found to infect neuronal cell lines such as SK-N-MC in a CD4-independent manner. 18 In fact, human neurons are more prone to the toxic effects of HIV-1 viral proteins and, subsequently released cytokines and chemokines.…”

mentioning

confidence: 99%

HIV-1 Nef is released in extracellular vesicles derived from astrocytes: evidence for Nef-mediated neurotoxicity

et al. 2017

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Human immunodeficiency virus-associated neurological disorders (HANDs) affect the majority of AIDS patients and are a significant problem among HIV-1-infected individuals who live longer because of combined anti-retroviral therapies. HIV-1 utilizes a number of viral proteins and subsequent cytokine inductions to unleash its toxicity on neurons. Among HIV-1 viral proteins, Nef is a small protein expressed abundantly in astrocytes of HIV-1-infected brains and has been suggested to have a role in the pathogenesis of HAND. In order to explore its effect in the central nervous system, HIV-1 Nef was expressed in primary human fetal astrocytes (PHFAs) using an adenovirus. Our results revealed that HIV-1 Nef is released in extracellular vesicles (EVs) derived from PHFA cells expressing the protein. Interestingly, HIV-1 Nef release in EVs was enriched significantly when the cells were treated with autophagy activators perifosine, tomaxifen, MG-132, and autophagy inhibitors LY294002 and wortmannin suggesting a novel role of autophagy signaling in HIV-1 Nef release from astrocytes. Next, Nef-carrying EVs were purified from astrocyte cultures and neurotoxic effects on neurons were analyzed. We observed that HIV-1 Nef-containing EVs were readily taken up by neurons as demonstrated by immunocytochemistry and immunoblotting. Furthermore, treatment of neurons with Nef-carrying EVs induced oxidative stress as evidenced by a decrease in glutathione levels. To further investigate its neurotoxic effects, we expressed HIV-1 Nef in primary neurons by adenoviral transduction. Intracellular expression of HIV-1 Nef caused axonal and neurite degeneration of neurons. Furthermore, expression of HIV-1 Nef decreased the levels of phospho-tau while enhancing total tau in primary neurons. In addition, treatment of primary neurons with Nef-carrying EVs suppressed functional neuronal action potential assessed by multielectrode array studies. Collectively, these data suggested that HIV-1 Nef can be a formidable contributor to neurotoxicity along with other factors, which leads to HAND in HIV-1-infected AIDS patients.

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“…88,89 There is also evidence suggesting a possible direct neuronal infection in infants. 90 Pathology reports confirm imaging data suggesting ventricular enlargement, myelin pallor, cerebral atrophy, and basal ganglia calcification. 91 Proinflammatory cytokines related to abdominal obesity have also been associated with progressive neurocognitive impairment in HIV-1 patients.…”

Section: Neuropathology and Neurotoxicology Of Hiv-1mentioning

confidence: 54%

Of Mice and Monkeys: Can Animal Models Be Utilized to Study Neurological Consequences of Pediatric HIV-1 Infection?

Carryl¹,

Swang²,

Lawrence³

et al. 2015

ACS Chem. Neurosci.

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Pediatric human immunodeficiency virus (HIV-1) infection remains a global health crisis. Children are much more susceptible to HIV-1 neurological impairments than adults, which can be exacerbated by coinfections. Neurological characteristics of pediatric HIV-1 infection suggest dysfunction in the frontal cortex as well as the hippocampus; limited MRI data indicate global cerebral atrophy, and pathological data suggest accelerated neuronal apoptosis in the cortex. An obstacle to pediatric HIV-1 research is a human representative model system. Host-species specificity of HIV-1 limits the ability to model neurological consequences of pediatric HIV-1 infection in animals. Several models have been proposed including neonatal intracranial injections of HIV-1 viral proteins in rats and perinatal simian immunodeficiency virus (SIV) infection of infant macaques. Nonhuman primate models recapitulate the complexity of pediatric HIV-1, neuropathogenesis while rodent models are able to elucidate the role specific viral proteins exert on neurodevelopment. Nonhuman primate models show similar behavioral and neuropathological characteristics to pediatric HIV-1 infection and offer a stage to investigate early viral mechanisms, latency reservoirs, and therapeutic interventions. Here we review the relative strengths and limitations of pediatric HIV-1 model systems.

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HIV-1 Infection of Neurons Might Account for Progressive HIV-1-Associated Encephalopathy in Children

Cited by 38 publications

References 37 publications

Viral parkinsonism

Viral parkinsonism

HIV-1 Nef is released in extracellular vesicles derived from astrocytes: evidence for Nef-mediated neurotoxicity

Of Mice and Monkeys: Can Animal Models Be Utilized to Study Neurological Consequences of Pediatric HIV-1 Infection?

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