HIV-1 coreceptors CCR5 and CXCR4 both mediate neuronal cell death but CCR5 paradoxically can also contribute to protection

Kaul, Marcus; Ma, Qiangzhong; Medders, Kathryn; Desai, Maya; Lipton, Stuart A.

doi:10.1038/sj.cdd.4402006

Cited by 147 publications

(254 citation statements)

References 51 publications

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“…Actually, the glutamate released by RANTES may contribute to the recruitment, the transmigration and the penetration in the CNS of T-lymphocytes bearing glutamate receptors, an event proposed to occur in defined phases of multiple sclerosis (Ganor et al, 2003;Sarchielli et al, 2007). On the other hand, RANTES has been reported to protect neurons from neurotoxic insults mediated by the HIV-1 viral protein gp120 (Kaul and Lipton, 1999;Kaul et al, 2007). Since the gp120-induced neuronal death depends on glutamate-dependent excitotoxic events, the hRANTES-mediated inhibition of the evoked glutamate release may be considered as one of the mechanisms underlying neuroprotection.…”

Section: Discussionmentioning

confidence: 99%

RANTES Modulates the Release of Glutamate in Human Neocortex

Musante¹,

Longordo²,

Neri³

et al. 2008

J. Neurosci.

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Section: Discussionmentioning

confidence: 99%

RANTES Modulates the Release of Glutamate in Human Neocortex

Musante¹,

Longordo²,

Neri³

et al. 2008

J. Neurosci.

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“…Rat mixed neuronal-glial cerebrocortical cell cultures were prepared from embryos of Sprague-Dawley rats at days 15 to 17 of gestation, as previously described by our group (44)(45)(46). In brief, cells were cultured in 35-mm dishes with poly-L-lysine-coated glass coverslips (1.87 ϫ 10 6 cells per dish) or in poly-L-lysine-coated clear-bottom 96-well plates for imaging (0.087 ϫ 10 6 cells per well) (BD Falcon, BD Biosciences, San Jose, CA).…”

Section: Methodsmentioning

confidence: 99%

Antiretrovirals, Methamphetamine, and HIV-1 Envelope Protein gp120 Compromise Neuronal Energy Homeostasis in Association with Various Degrees of Synaptic and Neuritic Damage

Sánchez

Varano

Rozieres

et al. 2016

Antimicrob Agents Chemother

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b HIV-1 infection frequently causes HIV-associated neurocognitive disorders (HAND) despite combination antiretroviral therapy (cART).Evidence is accumulating that components of cART can themselves be neurotoxic upon long-term exposure. In addition, abuse of psychostimulants, such as methamphetamine, seems to aggravate HAND and compromise antiretroviral therapy. However, the combined effect of virus and recreational and therapeutic drugs on the brain is poorly understood. Therefore, we exposed mixed neuronal-glial cerebrocortical cells to antiretrovirals (ARVs) (zidovudine [AZT], nevirapine [NVP], saquinavir [SQV], and 118-D-24) of four different pharmacological categories and to methamphetamine and, in some experiments, the HIV-1 gp120 protein for 24 h and 7 days. Subsequently, we assessed neuronal injury by fluorescence microscopy, using specific markers for neuronal dendrites and presynaptic terminals. We also analyzed the disturbance of neuronal ATP levels and assessed the involvement of autophagy by using immunofluorescence and Western blotting. ARVs caused alterations of neurites and presynaptic terminals primarily during the 7-day incubation and depending on the specific compounds and their combinations with and without methamphetamine. Similarly, the loss of neuronal ATP was context specific for each of the drugs or combinations thereof, with and without methamphetamine or viral gp120. Loss of ATP was associated with activation of AMP-activated protein kinase (AMPK) and autophagy, which, however, failed to restore normal levels of neuronal ATP. In contrast, boosting autophagy with rapamycin prevented the long-term drop of ATP during exposure to cART in combination with methamphetamine or gp120. Our findings indicate that the overall positive effect of cART on HIV infection is accompanied by detectable neurotoxicity, which in turn may be aggravated by methamphetamine.

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“…The neuroinflammatory response can limit virus replication through production of type I interferons and recruitment of virus-specific T cells to the CNS (5,9,12,15,19). However, the neuroinflammatory response can also lead to chronic gliosis, the production of cytokines that are toxic to neurons, and the recruitment of virus-infected cells to the CNS (6,8,18,35). Understanding the relationship between the innate immune response and viral disease is essential in order to manipulate this response to control virus infection in the CNS.…”

mentioning

confidence: 99%

Neuropeptide Y Has a Protective Role during Murine Retrovirus-Induced Neurological Disease

Butchi

Woods

et al. 2010

J Virol

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Viral infections in the central nervous system (CNS) can lead to neurological disease either directly by infection of neurons or indirectly through activation of glial cells and production of neurotoxic molecules.Understanding the effects of virus-mediated insults on neuronal responses and neurotrophic support is important in elucidating the underlying mechanisms of viral diseases of the CNS. In the current study, we examined the expression of neurotrophin-and neurotransmitter-related genes during infection of mice with neurovirulent polytropic retrovirus. In this model, virus-induced neuropathogenesis is indirect, as the virus predominantly infects macrophages and microglia and does not productively infect neurons or astrocytes. Virus infection is associated with glial cell activation and the production of proinflammatory cytokines in the CNS. In the current study, we identified increased expression of neuropeptide Y (NPY), a pleiotropic growth factor which can regulate both immune cells and neuronal cells, as a correlate with neurovirulent virus infection. Increased levels of Npy mRNA were consistently associated with neurological disease in multiple strains of mice and were induced only by neurovirulent, not avirulent, virus infection. NPY protein expression was primarily detected in neurons near areas of virus-infected cells. Interestingly, mice deficient in NPY developed neurological disease at a faster rate than wild-type mice, indicating a protective role for NPY. Analysis of NPY-deficient mice indicated that NPY may have multiple mechanisms by which it influences virus-induced neurological disease, including regulating the entry of virus-infected cells into the CNS.

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HIV-1 coreceptors CCR5 and CXCR4 both mediate neuronal cell death but CCR5 paradoxically can also contribute to protection

Cited by 147 publications

References 51 publications

RANTES Modulates the Release of Glutamate in Human Neocortex

RANTES Modulates the Release of Glutamate in Human Neocortex

Antiretrovirals, Methamphetamine, and HIV-1 Envelope Protein gp120 Compromise Neuronal Energy Homeostasis in Association with Various Degrees of Synaptic and Neuritic Damage

Neuropeptide Y Has a Protective Role during Murine Retrovirus-Induced Neurological Disease

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