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Viral infection of the dorsal root ganglion

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
Paul R Kinchington, William F Goins
Pain and post-herpetic neuralgia (PHN) are common and highly distressing complications of herpes zoster that remain a significant public health concern and in need of improved therapies. Zoster results from reactivation of the herpesvirus varicella zoster virus (VZV) from a neuronal latent state established at the primary infection (varicella). PHN occurs in some one fifth to one third of zoster cases with severity, incidence, and duration of pain increasing with rising patient age. While VZV reactivation and the ensuing ganglionic damage trigger the pain response, the mechanisms underlying protracted PHN are not understood, and the lack of an animal model of herpes zoster (reactivation) makes this issue more challenging...
December 2011: Journal of Neurovirology
Jason J Chen, Anne A Gershon, Zhishan Li, Robert A Cowles, Michael D Gershon
Case reports have linked varicella-zoster virus (VZV) to gastrointestinal disorders, including severe abdominal pain preceding fatal varicella and acute colonic pseudoobstruction (Ogilvie's syndrome). Because we had previously detected DNA and transcripts encoding latency-associated VZV gene products in the human gut, we sought to determine whether latent VZV is present in the human enteric nervous system (ENS) and, if so, to identify the cells in which it is located and its route to the bowel. Neither DNA, nor transcripts encoding VZV gene products, could be detected in resected gut from any of seven control children (<1 year old) who had not received the varicella vaccine or experienced varicella; however, VZV DNA and transcripts were each found to be present in resected bowel from 6/6 of children with a past history of varicella and in that of 6/7 of children who received the varicella vaccine...
December 2011: Journal of Neurovirology
Victoria A Laast, Beom Shim, Lisa M Johanek, Jamie L Dorsey, Peter E Hauer, Patrick M Tarwater, Robert J Adams, Carlos A Pardo, Justin C McArthur, Matthias Ringkamp, Joseph L Mankowski
Peripheral neuropathy is the most common neurological complication of HIV-1 infection, affecting over one-third of infected individuals, including those treated with antiretroviral therapy. To study the pathogenesis of HIV-induced peripheral nervous system disease, we established a model in which SIV-infected macaques developed changes closely resembling alterations reported in components of the sensory pathway in HIV-infected individuals. Significant declines in epidermal nerve fiber density developed in SIV-infected macaques, similar to that of HIV-infected individuals with neuropathy...
November 2011: American Journal of Pathology
Xianxun Chi, Tohti Amet, Daniel Byrd, Kuei-Hua Chang, Kavita Shah, Ningjie Hu, Ayslinn Grantham, Sishun Hu, Jianhong Duan, Feng Tao, Grant Nicol, Qigui Yu
The vast majority of people living with human immunodeficiency virus type 1 (HIV-1) have pain syndrome, which has a significant impact on their quality of life. The underlying causes of HIV-1-associated pain are not likely attributable to direct viral infection of the nervous system due to the lack of evidence of neuronal infection by HIV-1. However, HIV-1 proteins are possibly involved as they have been implicated in neuronal damage and death. The current study assesses the direct effects of HIV-1 Tat, one of potent neurotoxic viral proteins released from HIV-1-infected cells, on the excitability and survival of rat primary dorsal root ganglion (DRG) neurons...
2011: PloS One
Hongwei Yu, Greg Fischer, Guangfu Jia, Jakob Reiser, Frank Park, Quinn H Hogan
BACKGROUND: Lentivector-mediated gene delivery into the dorsal root ganglion (DRG) is a promising method for exploring pain pathophysiology and for genetic treatment of chronic neuropathic pain. In this study, a series of modified lentivector particles with different cellular promoters, envelope glycoproteins, and viral accessory proteins were generated to evaluate the requirements for efficient transduction into neuronal cells in vitro and adult rat DRG in vivo. RESULTS: In vitro, lentivectors expressing enhanced green fluorescent protein (EGFP) under control of the human elongation factor 1α (EF1α) promoter and pseudotyped with the conventional vesicular stomatitis virus G protein (VSV-G) envelope exhibited the best performance in the transfer of EGFP into an immortalized DRG sensory neuron cell line at low multiplicities of infection (MOIs), and into primary cultured DRG neurons at higher MOIs...
2011: Molecular Pain
Rachel E Allavena, Bhavika Desai, David Goodwin, Tansi Khodai, Helen Bright
Herpes simplex virus type 2 (HSV-2), a ubiquitous human pathogen associated with genital infections, is neurotropic. It establishes latent infections in local dorsal root ganglia from which it reactivates causing recurrent lesions and frequent episodes of viral shedding. Herpes simplex virus type 2 can also be transmitted from mother to child during birth, causing major neonatal complications including encephalitis. Animal models of HSV-2 genital infection are well described and used for testing of therapies; little is known about animal models of HSV-2-induced encephalitis...
August 2011: Journal of Neuropathology and Experimental Neurology
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