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Viral infection of the dorsal root ganglion

Yan Wang, Yingwei Gao, Quan Tian, Qi Deng, Yangbo Wang, Tian Zhou, Qiang Liu, Kaidi Mei, Yingping Wang, Huiqing Liu, Ruining Ma, Yuqiang Ding, Weifang Rong, Jinke Cheng, Jing Yao, Tian-Le Xu, Michael X Zhu, Yong Li
Although TRPV1 channels represent a key player of noxious heat sensation, the precise mechanisms for thermal hyperalgesia remain unknown. We report here that conditional knockout of deSUMOylation enzyme, SENP1, in mouse dorsal root ganglion (DRG) neurons exacerbated thermal hyperalgesia in both carrageenan- and Complete Freund's adjuvant-induced inflammation models. TRPV1 is SUMOylated at a C-terminal Lys residue (K822), which specifically enhances the channel sensitivity to stimulation by heat, but not capsaicin, protons or voltage...
April 18, 2018: Nature Communications
Priyanka Chauhan, Wen S Sheng, Shuxian Hu, Sujata Prasad, James R Lokensgard
BACKGROUND: Peripheral neuropathy is currently the most common neurological complication in HIV-infected individuals, occurring in 35-50% of patients undergoing combination anti-retroviral therapy. Data have shown that distal symmetric polyneuropathy develops in mice by 6 weeks following infection with the LP-BM5 retrovirus mixture. Previous work from our laboratory has demonstrated that glial cells modulate antiviral T-cell effector responses through the programmed death (PD)-1: PD-L1 pathway, thereby limiting the deleterious consequences of unrestrained neuroinflammation...
March 5, 2018: Journal of Neuroinflammation
Danielle M LaPaglia, Matthew R Sapio, Peter D Burbelo, Jean Thierry-Mieg, Danielle Thierry-Mieg, Stephen J Raithel, Christopher E Ramsden, Michael J Iadarola, Andrew J Mannes
Background The trigeminal ganglion contains neurons that relay sensations of pain, touch, pressure, and many other somatosensory modalities to the central nervous system. The ganglion is also a reservoir for latent herpes virus 1 infection. To gain a better understanding of molecular factors contributing to migraine and headache, transcriptome analyses were performed on postmortem human trigeminal ganglia. Methods RNA-Seq measurements of gene expression were conducted on small sub-regions of 16 human trigeminal ganglia...
January 1, 2017: Cephalalgia: An International Journal of Headache
Kazunori Kimitsuki, Kentaro Yamada, Nozomi Shiwa, Satoshi Inoue, Akira Nishizono, Chun-Ho Park
Most studies on rabies virus pathogenesis in animal models have employed fixed rabies viruses, and the results of those employing street rabies viruses have been inconsistent. Therefore, to clarify the pathogenesis of street rabies virus (1088 strain) in mice, 10(6) focus forming units were inoculated into the right hindlimb of ddY mice (6 weeks, female). At 3 days postinoculation (DPI), mild inflammation was observed in the hindlimb muscle. At 5 DPI, ganglion cells in the right lumbosacral spinal dorsal root ganglia showed chromatolysis...
June 10, 2017: Journal of Veterinary Medical Science
Massillamani Francis, Kailasam Subramanian, S Leena Sankari, Venkata Lakshmi Aparna Potluri, Akila Prabakaran
Herpes Zoster (HZ) is an acute, self-limiting, neuro cutaneous viral infection caused by the reactivation of the Varicella Zoster Virus (VZV) that remains latent in the dorsal root ganglion. About 50% of occurrence is seen in older age groups and immunocompromised patients. Less than 5% occur in children. HZ is characterized by the unilateral pain, burning and tingling sensation followed by the vesicular eruptions limited to the single dermatome that are innervated by the single cranial ganglion, sometimes it leads to Post Herpetic Neuralgia (PHN)...
January 2017: Journal of Clinical and Diagnostic Research: JCDR
F Pfaff, K Schlottau, S Scholes, A Courtenay, B Hoffmann, D Höper, M Beer
In June 2013, a 4-year-old Welsh Mountain ewe and in March 2014 a 10-day-old lamb of the same breed and the same flock presented progressive neurological signs including depressed sensorium, tremor, and unusual behaviour. Neuropathological examination of the brain and spinal cord detected non-suppurative polioencephalomyelitis and dorsal root ganglionitis, characteristic of a neurotropic viral agent in both sheep. Metagenomic analysis of different tissue samples from both animals identified a novel Ovine Astrovirus (OvAstV)...
June 2017: Transboundary and Emerging Diseases
Silvia Piccinotti, Sean P J Whelan
The single glycoprotein (G) of rabies virus (RABV) dictates all viral entry steps from receptor engagement to membrane fusion. To study the uptake of RABV into primary neuronal cells in culture, we generated a recombinant vesicular stomatitis virus in which the G protein was replaced with that of the neurotropic RABV CVS-11 strain (rVSV CVS G). Using microfluidic compartmentalized culture, we examined the uptake of single virions into the termini of primary neurons of the dorsal root ganglion and ventral spinal cord...
July 2016: PLoS Pathogens
Brent Stanfield, Konstantin Gus Kousoulas
Herpes simplex virus type-1 (HSV-1) and its closely related type-2 (HSV-2) viruses cause important clinical manifestations in humans including acute ocular disease and genital infections. These viruses establish latency in the trigeminal ganglionic and dorsal root neurons, respectively. Both viruses are widespread among humans and can frequently reactivate from latency causing disease. Currently, there are no vaccines available against herpes simplex viral infections. However, a number of promising vaccine approaches are being explored in pre-clinical investigations with few progressing to early phase clinical trials...
September 1, 2015: Current Clinical Microbiology Reports
Russell J Diefenbach, April Davis, Monica Miranda-Saksena, Marian A Fernandez, Barbara J Kelly, Cheryl A Jones, Jennifer H LaVail, Jing Xue, Joey Lai, Anthony L Cunningham
UNLABELLED: The alphaherpesviral envelope protein pUS9 has been shown to play a role in the anterograde axonal transport of herpes simplex virus 1 (HSV-1), yet the molecular mechanism is unknown. To address this, we used an in vitro pulldown assay to define a series of five arginine residues within the conserved pUS9 basic domain that were essential for binding the molecular motor kinesin-1. The mutation of these pUS9 arginine residues to asparagine blocked the binding of both recombinant and native kinesin-1...
December 9, 2015: Journal of Virology
R K Mattila, K Harila, S M Kangas, H Paavilainen, A M Heape, I J Mohr, V Hukkanen
After a primary lytic infection at the epithelia, herpes simplex virus type 1 (HSV-1) enters the innervating sensory neurons and translocates to the nucleus, where it establishes a quiescent latent infection. Periodically, the virus can reactivate and the progeny viruses spread back to the epithelium. Here, we introduce an embryonic mouse dorsal root ganglion (DRG) culture system, which can be used to study the mechanisms that control the establishment, maintenance and reactivation from latency. Use of acyclovir is not necessary in our model...
August 2015: Journal of General Virology
Wafa Kammouni, Heidi Wood, Ali Saleh, Camila M Appolinario, Paul Fernyhough, Alan C Jackson
Our previous studies in an experimental model of rabies showed neuronal process degeneration in association with severe clinical disease. Cultured adult rodent dorsal root ganglion neurons infected with challenge virus standard (CVS)-11 strain of rabies virus (RABV) showed axonal swellings and reduced axonal growth with evidence of oxidative stress. We have shown that CVS infection alters a variety of mitochondrial parameters and increases reactive oxygen species (ROS) production and mitochondrial Complex I activity vs...
August 2015: Journal of Neurovirology
Travis Rudd, Bryan Y Chai, Raffi Gurunluoglu, Mark Glasgow
Varicella zoster virus (VZV) is the agent that causes chicken pox, a common childhood infection that characteristically presents as vesicular rashes affecting the trunk and head. After the primary infection has resolved, VZV lies dormant in the spinal dorsal root ganglia or extramedullary cranial nerve ganglia until reactivation results in herpes zoster (shingles). The sensory nerves of the trunk, as in classic shingles, and the fifth cranial nerve, as in trigeminal zoster, are the most frequently affected...
October 2014: Journal of Oral and Maxillofacial Surgery
Ana Maria Low-Calle, Jeanette Prada-Arismendy, Jaime E Castellanos
Herpes simplex virus type 1 (HSV-1) causes a lytic infection in epithelial cells before being captured and moved via retrograde axonal transport to the nuclei of the sensory neurons of the trigeminal ganglion or dorsal root, where it establishes a latent infection. HSV-1 infection induces an antiviral response through the production of Beta Interferon (IFN-β) in infected trigeminal ganglia. The aim of this work was to characterize the response induced by IFN-β in neuron-enriched trigeminal ganglia primary cultures infected with HSV-1...
February 13, 2014: Virus Research
C A Webber, J Salame, G-L S Luu, S Acharjee, A Ruangkittisakul, J A Martinez, H Jalali, R Watts, K Ballanyi, G F Guo, D W Zochodne, C Power
Distal sensory polyneuropathy (DSP) with associated neuropathic pain is the most common neurological disorder affecting patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Viral protein R (Vpr) is a neurotoxic protein encoded by HIV-1 and secreted by infected macrophages. Vpr reduces neuronal viability, increases cytosolic calcium and membrane excitability of cultured dorsal root ganglion (DRG) sensory neurons, and is associated with mechanical allodynia in vivo. A clinical trial with HIV/AIDS patients demonstrated that nerve growth factor (NGF) reduced the severity of DSP-associated neuropathic pain, a problem linked to damage to small diameter, potentially NGF-responsive fibers...
November 12, 2013: Neuroscience
Wenlong Huang, Margarita Calvo, Kersti Karu, Hans R Olausen, Gabriella Bathgate, Kenji Okuse, David L H Bennett, Andrew S C Rice
HIV-associated sensory neuropathy is the most frequent manifestation of HIV disease, afflicting 40-50% of patients whose HIV disease is otherwise controlled by antiretroviral therapy. It often presents with significant neuropathic pain and is consistently associated with previous exposure to nucleoside reverse transcriptase inhibitors including stavudine (d4T), which is widely used in resource-limited settings. Here we investigated complex pain-related behaviours associated with d4T treatment using ethologically relevant thigmotaxis and burrowing behaviours in adult rats...
April 2013: Pain
Leigh Zerboni, Xibing Che, Mike Reichelt, Yanli Qiao, Haidong Gu, Ann Arvin
The tropism of herpes simplex virus (HSV-1) for human sensory neurons infected in vivo was examined using dorsal root ganglion (DRG) xenografts maintained in mice with severe combined immunodeficiency (SCID). In contrast to the HSV-1 lytic infectious cycle in vitro, replication of the HSV-1 F strain was restricted in human DRG neurons despite the absence of adaptive immune responses in SCID mice, allowing the establishment of neuronal latency. At 12 days after DRG inoculation, 26.2% of human neurons expressed HSV-1 protein and 13...
March 2013: Journal of Virology
Brian Yordy, Akiko Iwasaki
Type I interferons (IFNs) are induced during most viral infections and are considered to be the primary and universal means of innate viral control. However, several other innate mechanisms, including autophagy, have recently been shown to play an important role in antiviral defense. In our recent study, we utilized a herpes simplex virus 1 (HSV-1) infection model to investigate the relationship between cell type and innate antiviral immune mechanisms. Our study demonstrates that dorsal root ganglion (DRG) neurons undergo an innate antiviral response to HSV-1 that differs from the antiviral program induced in mitotic cells in three distinct ways...
February 1, 2013: Autophagy
M Papini
Genital herpes simplex virus infection is a recurrent, lifelong disease with no cure. The strongest predictor for infection is a person's number of lifetime sex partners. HSV-2 is the commonest responsible, although infections caused by HSV-1 are rapidly increasing, particularly in adolescents, women and men who have sex with men. The natural history includes first-episode of mucocutaneous infection, establishment of latency in the dorsal root ganglion, and subsequent reactivation. Most infections are transmitted via asymptomatic viral shedding...
October 2012: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
Corey Horien, Charles Grose
Varicella-zoster virus (VZV) is a neurotropic herpesvirus, which can cause a variety of complications during varicella infections. These range from meningoencephalitis to polyneuritis to retinitis. After primary VZV infection, VZV enters the dorsal root ganglia in a latent state. Reactivation from latency leads to zoster. The velocity of VZV is 13 cm per day, as the virus travels from ganglion to skin. The live attenuated varicella vaccine virus is markedly less neurovirulent than the wild-type virus. Nevertheless, a few cases of herpes zoster due to the vaccine virus have been documented...
September 2012: Seminars in Pediatric Neurology
Yan-Chao Li, Wan-Zhu Bai, Norio Hirano, Tsuyako Hayashida, Tsutomu Hashikawa
Swine hemagglutinating encephalomyelitis virus (HEV) has been shown to have a capability to gain access to the cell bodies of sensory neurons after peripheral inoculation, resulting in ganglionic infection. It is not clearly understood how this virus is replicated within and released from the sensory neurons, and it remains to know how satellite cells response to the HEV invasion. By ultrastructurally examining HEV-infected rat dorsal root ganglia, we found that HEV in the cell bodies of infected neurons budded from endoplasmic reticulum-Golgi intermediate compartments, and were assembled either individually within small vesicles or in groups within large vesicles...
February 2012: Virus Research
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