Olfactory transmission of neurotropic viruses

Mori, Isamu; Nishiyama, Yukihiro; Yokochi, Takashi; Kimura, Yoshinobu

doi:10.1080/13550280590922793

Cited by 191 publications

(159 citation statements)

References 76 publications

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“…The most likely routes include retrograde transport through the olfactory or trigeminal nerves [9,12,13], or via hematogenous dissemination. The viral tropism for the orbitofrontal and mesiotemporal lobes argues against hematogenous dissemination in most cases.…”

Section: Introductionmentioning

confidence: 99%

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Herpes Simplex Virus-1 Encephalitis in Adults: Pathophysiology, Diagnosis, and Management

2016

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Herpetic infections have plagued humanity for thousands of years, but only recently have advances in antiviral medications and supportive treatments equipped physicians to combat the most severe manifestations of disease. Prompt recognition and treatment can be lifesaving in the care of patients with herpes simplex-1 virus encephalitis, the most commonly identified cause of sporadic encephalitis worldwide. Clinicians should be able to recognize the clinical signs and symptoms of the infection and familiarize themselves with a rational diagnostic approach and therapeutic modalities, as early recognition and treatment are key to improving outcomes. Clinicians should also be vigilant for the development of acute complications, including cerebral edema and status epilepticus, as well as chronic complications, including the development of autoimmune encephalitis associated with antibodies to the N-methyl-D-aspartate receptor and other neuronal cell surface and synaptic epitopes. Herein, we review the pathophysiology, differential diagnosis, and clinical and radiological features of herpes simplex virus-1 encephalitis in adults, including a discussion of the most common complications and their treatment. While great progress has been made in the treatment of this life-threatening infection, a majority of patients will not return to their previous neurologic baseline, indicating the need for further research efforts aimed at improving the long-term sequelae.

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Section: Introductionmentioning

confidence: 99%

“…There is some evidence to support olfactory spread to the CNS in humans, but definitive data are lacking [12,[14][15][16]. The trigeminal nerve innervates the meninges, and spread to the orbitofrontal and mesiotemporal lobes could also occur through this route [17].…”

Section: Introductionmentioning

confidence: 99%

Herpes Simplex Virus-1 Encephalitis in Adults: Pathophysiology, Diagnosis, and Management

2016

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“…inoculation VSV can readily infect olfactory receptor neurons (7,9). Because the cell body of olfactory receptor neurons is located in the nasal mucosa, whereas their axons project into the olfactory bulb, virus can easily enter the CNS (12). In contrast to i.n.-or i.v.-infected mice, intracerebrally inoculated mice rapidly develop fatal disease (13), probably because once virus entered the brain it cannot easily brought under control.…”

mentioning

confidence: 99%

Local Type I IFN Receptor Signaling Protects against Virus Spread within the Central Nervous System

Detje

Meyer

Schmidt

et al. 2009

The Journal of Immunology

137

144

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Several neurotropic viruses such as vesicular stomatitis virus (VSV) induce peripheral neutralizing Ab responses and still can infect cells within the CNS. To address whether local type I IFN receptor (IFNAR) triggering plays a role in controlling virus replication within the brain, we generated mice with a cell type-specific IFNAR deletion in neuroectodermal cells of the CNS (NesCre+/−IFNARflox/flox). Intranasal VSV infection with 103 PFU was well tolerated by wild-type mice, whereas conventional IFNAR−/− mice died within 2–3 days. In contrast, brain-specific NesCre+/−IFNARflox/flox mice survived until day 5–6 and then became hemiplegic and died. Terminally ill NesCre+/−IFNARflox/flox mice showed 10- to 100-fold higher virus loads in the brain than IFNAR−/− mice, whereas little or no virus was found in other organs. In wild-type animals, virus could be reisolated only from the olfactory bulb until day 6 where also STAT1 activation as a measure of IFNAR triggering was detected. Virus infection was found exclusively in glomerular structures of the olfactory bulb, whereas surrounding cells that showed STAT1 phosphorylation as a measure of IFNAR trigging were free of virus. Our data indicate that upon intranasal VSV instillation, early and localized IFNAR triggering in the glomerular layer of the olfactory bulb is critically required to prevent viral spread over the entire CNS and thus confers survival.

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“…This problem might be solved if instead of volatility we focus on molecular weight, which is relevant in both air and water; thus, perhaps the vomeronasal system mediates responses to high-molecular-weight molecules, and the olfactory organ detects low-molecular-weight compounds [8]. Even so, molecules of varying molecular weights would presumably have access to both the olfactory and vomeronasal epithelia in aquatic animals, and recent data suggest that large particles, such as viruses, can reach the olfactory epithelium in terrestrial animals [51]. Few studies have compared the movements of large and small molecules in external environments and inside chemosensory organs in either air or water, yet this information is potentially crucial for our understanding of vomeronasal system function.…”

Section: Vomeronasal Responses To Non-pheromonal Stimulimentioning

confidence: 99%