Differential effects of HIV infected macrophages on dorsal root ganglia neurons and axons

Hahn, Katrin; Robinson, B.; Anderson, Caroline F.; Li, Wenxue; Pardo, Carlos A.; Morgello, Susan; Simpson, David M.; Nath, Avindra

doi:10.1016/j.expneurol.2007.06.015

Cited by 54 publications

(43 citation statements)

References 38 publications

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“…Because of morphological similarities with diabetic neuropathy, we have hypothesized that oxidative stress may also play a key role in degeneration of neuronal processes in rabies virus infection. The importance of oxidative stress during viral infections has been recognized for over a decade (25), and oxidative injury has been shown to be an important component in HIV infec- tion (7,34), particularly in HIV dementia (34), and also in experimental acute encephalitis caused by herpes simplex virus type 1 in mice (31).…”

Section: Discussionmentioning

confidence: 99%

Role of Oxidative Stress in Rabies Virus Infection of Adult Mouse Dorsal Root Ganglion Neurons

Jackson

Kammouni

Zherebitskaya

et al. 2010

J Virol

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Rabies virus infection of dorsal root ganglia (DRG) was studied in vitro with cultured adult mouse DRG neurons. Recent in vivo studies of transgenic mice that express the yellow fluorescent protein indicate that neuronal process degeneration, involving both dendrites and axons, occurs in mice infected with the challenge virus standard (CVS) strain of rabies virus by footpad inoculation. Because of the similarities of the morphological changes in experimental rabies and in diabetic neuropathy and other diseases, we hypothesize that neuronal process degeneration occurs as a result of oxidative stress. DRG neurons were cultured from adult ICR mice. Two days after plating, they were infected with CVS. Immunostaining was evaluated with CVS-and mock-infected cultures for neuron specific ␤-tubulin, rabies virus antigen, and amino acid adducts of 4-hydroxy-2-nonenal (4-HNE) (marker of lipid peroxidation and hence oxidative stress). Neuronal viability (by trypan blue exclusion), terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining, and axonal growth were also assessed with the cultures. CVS infected 33 to 54% of cultured DRG neurons. Levels of neuronal viability and TUNEL staining were similar in CVS-and mock-infected DRG neurons. There were significantly more 4-HNE-labeled puncta at 2 and 3 days postinfection in CVS-infected cultures than in mock-infected cultures, and axonal outgrowth was reduced at these time points in CVS infection. Axonal swellings with 4-HNE-labeled puncta were also associated with aggregations of actively respiring mitochondria. We have found evidence that rabies virus infection in vitro causes axonal injury of DRG neurons through oxidative stress. Oxidative stress may be important in vivo in rabies and may explain previous observations of the degeneration of neuronal processes.Rabies is an acute viral infection of the central nervous system (CNS) that is usually fatal in humans and animals (10). Despite its lethality, under natural conditions only relatively mild histopathological lesions are typically found in association with a paucity of degenerative neuronal changes (9, 21). Li et al. (13) showed severe destruction and disorganization of axons and disruption of synaptic structures in silver-stained hippocampal sections from mice infected intracerebrally with the pathogenic N2C strain of rabies virus. Infection with the challenge virus standard (CVS) strain of rabies virus has recently been evaluated using hindlimb footpad inoculation in adult transgenic mice expressing yellow fluorescent protein (26). In this model, dendritic beading and axonal swellings were prominent, and neuronal process degeneration appeared to account for the severe clinical disease and fatal outcome. The axonal swellings exhibited striking morphological similarities to the neurodegenerative changes that occur in the axons of neurons in diabetic sensory and autonomic neuropathy and in human immunodeficiency virus (HIV) infection (4,12,24,35). Studies of cultured adult dorsal root ganglio...

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Section: Discussionmentioning

confidence: 99%

Role of Oxidative Stress in Rabies Virus Infection of Adult Mouse Dorsal Root Ganglion Neurons

Jackson

Kammouni

Zherebitskaya

et al. 2010

J Virol

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“…Two possible neuropathogenetic mechanisms have been proposed; the direct effect of HIV or HIV proteins such as gp120 on DRGs [33][34][35] and the indirect neurotoxicity of products secreted by activated macrophages [32]. The later assumption is underlined by our observation that supernatants from HIV-infected macrophages induce neuritic retraction in DRG culture, suggesting that activated macrophages may secrete neurotoxic mediators [36].…”

Section: Hiv-dspmentioning

confidence: 88%

HIV Associated Neuropathies

Hahn¹,

Husstedt²

2011

HIV Infection in the Era of Highly Active Antiretroviral Treatment and Some of Its Associated Complications

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“…Previous research suggests that monocyte/macrophages traffic to the dorsal root ganglia (DRG) and inflict damage during HIV and SIV infection [42,[44][45][46]. These studies used CD68 + or Iba-1 to characterize resident macrophages in the DRG [42,46,47].…”

Section: Monocyte Traffic and Activation In Drg During Siv Peripheralmentioning

confidence: 99%

Macrophage Polarization in AIDS: Dynamic Interface between Anti-Viral and Anti-Inflammatory Macrophages during Acute and Chronic Infection

Burdo

Walker

Williams

2015

J Clin Cell Immunol

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Monocyte and macrophage inflammation in parenchymal tissues during acute and chronic HIV and SIV infection plays a role in early anti-viral immune responses and later in restorative responses. Macrophage polarization is observed in such responses in the central nervous system (CNS) and the heart and cardiac vessels that suggest early responses are M1 type antiviral responses, and later responses favor M2 restorative responses. Macrophage polarization is unique to different tissues and is likely dictated as much by the local microenvironment as well as other inflammatory cells involved in the viral responses. Such polarization is found in HIV infected humans, and the SIV infected animal model of AIDS, and occurs even with effective anti-retroviral therapy. Therapies that directly target macrophage polarization in HIV infection have recently been implemented, as have therapies to directly block traffic and accumulation of macrophages in tissues.

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Differential effects of HIV infected macrophages on dorsal root ganglia neurons and axons

Cited by 54 publications

References 38 publications

Role of Oxidative Stress in Rabies Virus Infection of Adult Mouse Dorsal Root Ganglion Neurons

Role of Oxidative Stress in Rabies Virus Infection of Adult Mouse Dorsal Root Ganglion Neurons

HIV Associated Neuropathies

Macrophage Polarization in AIDS: Dynamic Interface between Anti-Viral and Anti-Inflammatory Macrophages during Acute and Chronic Infection

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