HIV Subtypes B and C gp120 and Methamphetamine Interaction: Dopaminergic System Implicates Differential Neuronal Toxicity

Samikkannu, Thangavel; Rao, K. Venkata; Salam, Abdul Ajees Abdul; Atluri, Venkata Subba Rao; Kaftanovskaya, Elena M.; Agudelo, Marisela; Pérez, Suray A.; Yoo, Changwon; Raymond, Andrea; Ding, Hong; Nair, Madhavan

doi:10.1038/srep11130

Cited by 16 publications

(15 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pain researchers have been interested in the role of glia in the regulation of pain since 1991, when Garrison and colleagues noticed an elevated GFAP staining density in chronic pain state, an event that was correlated with hyperalgesia and indicated astrocyte participation in peripheral nerve injury-induced neuropathy (Garrison et al, 1991). Serious injuries and not minor acute pains are able to stimulate dynamic alterations in glial cell functioning (Samikkannu et al, 2015).…”

Section: Pain and Glial Cellsmentioning

confidence: 99%

Opioids, gliosis and central immunomodulation

2018

View full text Add to dashboard Cite

Neuropathic pain is a common health problem that affects millions of people worldwide. Despite being studied extensively, the cellular and molecular events underlying the central immunomodulation and the pathophysiology of neuropathic pain is still controversial. The idea that 'glial cells are merely housekeepers' is incorrect and with respect to initiation and maintenance of neuropathic pain, microglia and astrocytes have important roles to play. Glial cells differentially express opioid receptors and are thought to be functionally modulated by the activation of these receptors. In this review, we discuss evidence for glia-opioid modulation of pain by focusing on the pattern of astrocyte and microglial activation throughout the progress of nerve injury/neuropathic pain. Activation of astrocytes and microglia is a key step in central immunomodulation in terms of releasing pro-inflammatory markers and propagation of a 'central immune response'. Inhibition of astrocytes before and after induction of neuropathic pain has been found to prevent and reverse neuropathic pain, respectively. Moreover, microglial inhibitors have been found to prevent (but not to reverse) neuropathic pain. As they are expressed by glia, opioid receptors are expected to have a role to play in neuropathic pain.

show abstract

Section: Pain and Glial Cellsmentioning

confidence: 99%

Opioids, gliosis and central immunomodulation

2018

View full text Add to dashboard Cite

show abstract

“…For example, conditioned-media from HIV-infected human macrophages is more potently neurotoxic to both rat and human neurons in groups from clade B HIV-1 than from clade C HIV-1 (71). A recent study addressing the neurotoxic mechanisms between clade B and clade C HIV gp120 demonstrated that the dopamine system is preferentially affected by HIV gp120 B but not by gp120 C (72). Specifically, clade B gp120 appears to promote neurotoxicity by impairing the expression of dopamine receptors (DRD-2), dopamine transporters (DAT), and the signaling proteins calcium/calmodulin kinases (CaMK) type 2 and 4 in astrocytes when compared to gp120 from clade C (72).…”

Section: Hiv-1 Gp120 Tropism and The Severity Of Neurovirulence And Nmentioning

confidence: 99%

“…A recent study addressing the neurotoxic mechanisms between clade B and clade C HIV gp120 demonstrated that the dopamine system is preferentially affected by HIV gp120 B but not by gp120 C (72). Specifically, clade B gp120 appears to promote neurotoxicity by impairing the expression of dopamine receptors (DRD-2), dopamine transporters (DAT), and the signaling proteins calcium/calmodulin kinases (CaMK) type 2 and 4 in astrocytes when compared to gp120 from clade C (72). Of particular interest, the downregulation of dopamine system proteins was synergistically induced by concomitant treatment with methamphetamine.…”

Section: Hiv-1 Gp120 Tropism and The Severity Of Neurovirulence And Nmentioning

confidence: 99%

“…Of particular interest, the downregulation of dopamine system proteins was synergistically induced by concomitant treatment with methamphetamine. However, in this mechanistic study, neurotoxicity was assessed using primary human astrocytes (72), and whether similar neurotoxic mechanisms are the case with neurons remains elusive. Not surprisingly, such differences in mediating neurotoxicity were located on the V3 and C3 regions.…”

Section: Hiv-1 Gp120 Tropism and The Severity Of Neurovirulence And Nmentioning

confidence: 99%

“…Not surprisingly, such differences in mediating neurotoxicity were located on the V3 and C3 regions. Computational analysis indicated that V3 and C3 variability led to a distinct spatial rearrangement of gp120 motifs between both clades (72). Genetic heterogeneity in HIV-1 env is not only critical for neurotropism and cell entry but also crucial for exerting potent neurotoxicity and for causing neuropathology.…”

Section: Hiv-1 Gp120 Tropism and The Severity Of Neurovirulence And Nmentioning

confidence: 99%

See 2 more Smart Citations

Envelope Gene Evolution and HIV-1 Neuropathogenesis

Vázquez-Santiago

Rivera‐Amill

2015

J Neuroinfect Dis

View full text Add to dashboard Cite

In the era of combined antiretroviral therapy (cART), HIV-associated neurocognitive disorders (HAND) account for 40 to 56% of all HIV+ cases. During the acute stage of HIV-1 infection (<6 months), the virus invades and replicates within the central nervous system (CNS). Compared to peripheral tissues, the local CNS cell population expresses distinct levels of chemokine receptors, which levels exert selective pressure on the invading virus. HIV-1 envelope (env) sequences recovered from the brains and cerebrospinal fluid (CSF) of neurocognitively impaired HIV+ subjects often display higher nucleotide variability as compared to non-impaired HIV+ subjects. Specifically, env evolution provides HIV-1 with the strategies to evade host immune response, to reduce chemokine receptor dependence, to increase co-receptor binding efficiency, and to potentiate neurotoxicity. The evolution of env within the CNS leads to changes that may result in the emergence of novel isolates with neurotoxic and neurovirulent features. However, whether specific factors of HIV-1 evolution lead to the emergence of neurovirulent and neurotropic isolates remains ill-defined. HIV-1 env evolution is an ongoing phenomenon that occurs independently of neurological and neurocognitive disease severity; thus HIV env evolution may play a pivotal and reciprocal role in the etiology of HAND. Despite the use of cART, the reactivation of latent viral reservoirs represents a clinical challenge because of the replenishment of the viral pool that may subsequently lead to persistent infection. Therefore, gaining a more complete understanding of how HIV-1 env evolves over the course of the disease should be considered for the development of future therapies aimed at controlling CNS burden, diminishing persistent viremia, and eradicating viral reservoirs. Here we review the current literature on the role of HIV-1 env evolution in the setting of HAND disease progression and on the impact of cART on the dynamics of viral evolution.

show abstract