Human immunodeficiency virus type 1 infection of the brain

Atwood, Walter J.; Berger, Joseph R.; Kaderman, R; Tornatore, Carlo; Major, Eugene O.

doi:10.1128/cmr.6.4.339

Cited by 103 publications

(23 citation statements)

References 366 publications

(300 reference statements)

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“…These resident macrophages of the brain are the ontogenetic and functional equivalent of macrophages in somatic tissues (29). Histopathological evidence suggests that microglia play an important role in the neuropathogenesis of HIV-1 infection within the CNS (30)(31)(32)(33). Permissive HIV-1 infection of the CNS occurs only in microglia, although astrocytes are also involved in HIV-1-related neuropathogenesis (34,35).…”

Section: Discussionmentioning

confidence: 99%

kappa opioid receptors in human microglia downregulate human immunodeficiency virus 1 expression.

Chao

Gekker

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

138

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Microglial cells, the resident macrophages of the brain, play an important role in the neuropathogenesis of human immunodeficiency virus type 1 (HIV-1), and recent studies suggest that opioid peptides regulate the function of macrophages from somatic tissues. We report herein the presence of ic opioid receptors (KORs) in human fetal microglia and inhibition of HIV-1 expression in acutely infected microglial cell cultures treated with KOR ligands. Using reverse transcriptase-polymerase chain reaction and sequencing analyses, we found that mRNA for the KOR was constitutively expressed in microglia and determined that the nucleotide sequence of the open reading frame was identical to that of the human brain KOR gene. The expression of KOR in microglial cells was confirmed by membrane binding of [31H]U69,593, a c-selective ligand, and by indirect immunofluorescence. Treatment of microglial cell cultures with U50,488 or U69,593 resulted in a dose-dependent inhibition of expression of the monocytotropic HIV-1 SF162 strain. This antiviral effect of the ic ligands was blocked by the specific KOR antagonist, nor-binaltrophimine. These findings suggest that c opioid agonists have immunomodulatory activity in the brain, and that these compounds could have potential in the treatment of HIV-1-associated encephalopathy.Activation of the three major types of opioid receptors (i.e., t,

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Section: Discussionmentioning

confidence: 99%

kappa opioid receptors in human microglia downregulate human immunodeficiency virus 1 expression.

Chao

Gekker

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

138

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“…These exogenous retroviruses can replicate within the central nervous system and cause neurological and psychiatric symptoms in some infected individuals. The clinical response to infection with HIV is determined, to some extent, by the genetic susceptibility of the infected individual (12)(13)(14).…”

mentioning

confidence: 99%

Retroviral RNA identified in the cerebrospinal fluids and brains of individuals with schizophrenia

Karlsson

Bachmann

Schröder

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

328

215

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S chizophrenia is a pervasive neuropsychiatric disease of uncertain etiology. In the United States, schizophrenia has a lifetime prevalence of greater than 1% and results in the annual expenditure of more than 65 billion dollars (1, 2). Family and adoption studies have demonstrated a significantly increased risk of schizophrenia in individuals who have a first-degree birth relative with this disease, indicating that there is a substantial genetic component in disease pathogenesis. Epidemiological studies have identified a number of environmental factors associated with the development of schizophrenia, including perinatal infections, winter-spring birth, household crowding, and upbringing in urban areas (3, 4). These genetic and environmental findings can be reconciled by the concept that the disease can result from infectious processes occurring in genetically susceptible individuals (5-8).Retroviruses have been hypothesized as one of the infectious agents involved in the pathogenesis of schizophrenia (9-11). Humans can be infected with retroviruses such as strains of human immunodeficiency virus (HIV) and human T-cell leukemia virus. These exogenous retroviruses can replicate within the central nervous system and cause neurological and psychiatric symptoms in some infected individuals. The clinical response to infection with HIV is determined, to some extent, by the genetic susceptibility of the infected individual (12-14).The human genome also contains many endogenous retroviral (HERV) elements, which have homology to known animal retroviruses. These elements probably arose from reverse transcriptase-mediated integration into the germ line of progenitors of Homo sapiens after exogenous retroviral infection. Many of the HERV sequences in the human genome are incomplete, although some full-length proviral genomic sequences have been identified. Some of these proviruses contain long open reading frames capable of encoding complete viral proteins and engendering viral particles (15)(16)(17)(18)(19)(20). The tissue-specific expression of HERVs has been associated with a number of chronic human diseases, including multiple sclerosis, diabetes, and autoimmune arthritis (21-23). We report the identification of retroviral sequences in cerebrospinal fluids (CSFs) obtained from individuals with recent-onset schizophrenia, and the differential transcriptional up-regulation of members of the HERV-W family of endogenous retroviruses in the postmortem frontal cortex of individuals with schizophrenia. Materials and Methods CSF Samples. Patients with new-onset schizophrenia.We obtained CSF samples from 35 previously healthy individuals (presenting to the Department of Psychiatry at the University of Heidelberg) with symptoms consistent with new-onset schizophrenia or schizoaffective disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Ed. (25). These individuals had not been admitted previously to the hospital for schizophrenia and were without manifestations of acute infectious, inflammatory,...

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“…[14][15][16][17] Loss of astrocytic antioxidant support may contribute to neuronal death. [18][19][20][21][22][23] The findings of one study suggest that Atm À/À astrocytes are unable to protect Purkinje cells against oxidative stress. 9 However, it is not clear how Atm À/À astrocytes fail to protect these neurons.…”

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confidence: 99%

ATM deficiency induces oxidative stress and endoplasmic reticulum stress in astrocytes

Liu

Stoica

Yan

et al. 2005

Laboratory Investigation

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ATM kinase, the product of the ataxia telangiectasia mutated (Atm) gene, is activated by genomic damage. ATM plays a crucial role in cell growth and development. Here we report that primary astrocytes isolated from ATMdeficient mice grow slowly, become senescent, and die in culture. However, before reaching senescence, these primary Atm À/À astrocytes, like Atm À/À lymphocytes, show increased spontaneous DNA synthesis. These astrocytes also show markers of oxidative stress and endoplasmic reticulum (ER) stress, including increased levels of heat shock proteins (HSP70 and GRP78), malondialdehyde adducts, Cu/Zn superoxide dismutase, procaspase 12 cleavage, and redox-sensitive phosphorylation of extracellular signal-regulated protein kinase 1 and 2 (ERK1/2). In addition, HSP70 and ERK1/2 phosphorylation are upregulated in the cerebella of ATMdeficient mice. This increase in ERK1/2 phosphorylation is seen primarily in cerebellar astrocytes, or Bergmann glia, near degenerating Purkinje cells. ERK1/2 activation and astrogliosis are also found in other parts of the brain, for example, the cortex. We conclude that ATM deficiency induces intrinsic growth defects, oxidative stress, ER stress, and ERKs activation in astrocytes.

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Human immunodeficiency virus type 1 infection of the brain

Cited by 103 publications

References 366 publications

kappa opioid receptors in human microglia downregulate human immunodeficiency virus 1 expression.

kappa opioid receptors in human microglia downregulate human immunodeficiency virus 1 expression.

Retroviral RNA identified in the cerebrospinal fluids and brains of individuals with schizophrenia

ATM deficiency induces oxidative stress and endoplasmic reticulum stress in astrocytes

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