Neurotrophic Factor Regulation of Human Immunodeficiency Virus Type 1 Replication in Human Blood-derived Macrophages Through Modulation of Coreceptor Expression

Harrold, Sharon M.; Dragic, Joanna M.; Brown, Sarah; Achim, Cristian L.

doi:10.1007/0-306-47611-8_5

Cited by 6 publications

(4 citation statements)

References 14 publications

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“…Indeed, this is consistent with the reported ability of αD11 mAb to inhibit NGF biological activity even at NGF molar excess. 11,12 It is noteworthy that the observed increase in the SPR signal for the 1:1 molar ratio, which also represents an internal control that no high-MM immunocomplexes are present at the concentration used in the experiment, is not observed for the 1:2 to 1:4 molar ratios. The bivalent nature of the whole immunoglobulin format used in the SPR analysis likely accounts for the increased binding due to the additional avidity component, which indeed does not allow a kinetic or a stoichiometric analysis.…”

Section: Neutralization Propertiesmentioning

confidence: 78%

“…8 Moreover, NGF has been shown to be an autocrine factor essential for the survival of macrophages infected with HIV. [9][10][11] Therefore, the involvement of NGF in many pathological states unrelated with the central nervous system raised the idea that NGF antagonists could have a therapeutic effect, in particular for presently intractable forms of pain.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Dissecting NGF Interactions with TrkA and p75 Receptors by Structural and Functional Studies of an Anti-NGF Neutralizing Antibody

Covaceuszach

Cassetta

Konarev

et al. 2008

Journal of Molecular Biology

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Section: Neutralization Propertiesmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Dissecting NGF Interactions with TrkA and p75 Receptors by Structural and Functional Studies of an Anti-NGF Neutralizing Antibody

Covaceuszach

Cassetta

Konarev

et al. 2008

Journal of Molecular Biology

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“…Support for this possibility has come from studies of macrophages showing that NGF may increase CXCR4 expression, the receptor for SDF and co-receptor to HIV (Samah et al 2008(Samah et al , 2009. While this might predict an increased susceptibility to infection, there is conflicting data on the role of NGF in HIV replication in macrophages (Garaci et al 1999;Harrold et al 2001;Samah et al 2009). Known interactions of the HIV protein Nef in macrophages suggested activation of signaling pathways associated with podosome formation that might be similar to the recently described effects of proNGF (Verollet et al 2015).…”

Section: Introductionmentioning

confidence: 93%

Opposing Effects of NGF and proNGF on HIV Induced Macrophage Activation

Williams¹,

Killebrew

Clary

et al. 2015

J Neuroimmune Pharmacol

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Macrophage and microglial activation by HIV in the central nervous system (CNS) triggers the secretion of soluble factors which damage neurons. Therapeutic approaches designed to restore cognitive function by suppressing this inflammatory activity have not yet been successful. Recent studies have indicated that the phenotype of macrophages is differentially controlled by the mature and pro form of nerve growth factor. These cells therefore may be highly responsive to the imbalance in pro versus mature neurotrophins often associated with neurodegenerative diseases. In this study we evaluated the interactions between neurotrophins and HIV induced macrophage activation. HIV stimulation of macrophages induced a neurotoxic phenotype characterized by the expression of podosomes, suppression of calcium spiking and increased neurotoxin production. The secretome of the activated macrophages revealed a bias toward anti-angiogenic like activity and increased secretion of MMP-9. Co-stimulation with NGF and HIV suppressed neurotoxin secretion, increased calcium spiking, suppressed podosome expression and reversed 86% of the proteins secreted in response to HIV, including MMP-9 and many growth factors. In contrast, co-stimulation of macrophages with proNGF not only failed to reverse the effects of HIV but increased the neurotoxic phenotype. These differential effects of proNGF and NGF on HIV activation provide a potential novel therapeutic avenue for controlling macrophage activation in response to HIV.

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“…27 It has also been suggested that increased BDNF levels in the CNS microenvironment could increase CCR5 expression which is capable of spreading viral infection. 28 This highlights the need for more studies to explain the mechanisms responsible for the opposite effects of BDNF expression in different brain regions.…”

Section: Bdnf and Viral Proteinsmentioning

confidence: 99%

<p>The Role of Brain Derived Neurotrophic Factor in HIV-Associated Neurocognitive Disorder: From the Bench-Top to the Bedside</p>

Michael

Mpofana

Ramlall

et al. 2020

NDT

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Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) remains prevalent in the anti-retroviral (ART) era. While there is a complex interplay of many factors in the neuropathogenesis of HAND, decreased neurotrophic synthesis has been shown to contribute to synaptic degeneration which is a hallmark of HAND neuropathology. Brain derived neurotrophic factor (BDNF) is the most abundant and synaptic-promoting neurotrophic factor in the brain and plays a critical role in both learning and memory. Reduced BDNF levels can worsen neurocognitive impairment in HIV-positive individuals across several domains. In this paper, we review the evidence from pre-clinical and clinical studies showing the neuroprotective roles of BDNF against viral proteins, effect on co-morbid mental health disorders, altered human microbiome and ART in HAND management. Potential applications of BDNF modulation in pharmacotherapeutic, cognitive and behavioral interventions in HAND are also discussed. Finally, research gaps and future research direction are identified with the aim of helping researchers to direct efforts to make these BDNF driven interventions improve the quality of life of patients living with HAND.

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Neurotrophic Factor Regulation of Human Immunodeficiency Virus Type 1 Replication in Human Blood-derived Macrophages Through Modulation of Coreceptor Expression

Cited by 6 publications

References 14 publications

Dissecting NGF Interactions with TrkA and p75 Receptors by Structural and Functional Studies of an Anti-NGF Neutralizing Antibody

Dissecting NGF Interactions with TrkA and p75 Receptors by Structural and Functional Studies of an Anti-NGF Neutralizing Antibody

Opposing Effects of NGF and proNGF on HIV Induced Macrophage Activation

<p>The Role of Brain Derived Neurotrophic Factor in HIV-Associated Neurocognitive Disorder: From the Bench-Top to the Bedside</p>

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