Recovery of Herpes-Simplex Virus from Human Trigeminal Ganglions

Baringer,; Swoveland, Peggy

doi:10.1056/nejm197303292881303

Cited by 622 publications

(139 citation statements)

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“…The virus then travels via retrograde transport to the sensory neurons, which are located in the TG. Here, HSV-1 establishes latency (18,19). Viral latency is characterized by the retention of a functional viral genome and very limited gene expression without the production of infectious virus particles (20).…”

Section: Discussionmentioning

confidence: 99%

Differential Involvement during Latent Herpes Simplex Virus 1 Infection of the Superior and Inferior Divisions of the Vestibular Ganglia: Implications for Vestibular Neuritis

Himmelein

Lindemann

Sinicina

et al. 2017

J Virol

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Controversy still surrounds both the etiology and pathophysiology of vestibular neuritis (VN). Especially uncertain is why the superior vestibular nerve (SVN) is more frequently affected than the inferior vestibular nerve (IVN), which is partially or totally spared. To address this question, we developed an improved method for preparing human vestibular ganglia (VG) and nerve. Subsequently, macro-and microanatomical as well as PCR studies were performed on 38 human ganglia from 38 individuals. The SVN was 2.4 mm longer than the IVN, and in 65% of the cases, the IVN ran in two separate bony canals, which was not the case for the SVN. Anastomoses between the facial and cochlear nerves were more common for the SVN (14/38 and 9/38, respectively) than for the IVN (7/38 and 2/38, respectively). Using reverse transcription-quantitative PCR (RT-qPCR), we found only a few latently herpes simplex virus 1 (HSV-1)-infected VG (18.4%). In cases of two separate neuronal fields, infected neurons were located in the superior part only. In summary, these PCR and micro-and macroanatomical studies provide possible explanations for the high frequency of SVN infection in vestibular neuritis.IMPORTANCE Vestibular neuritis is known to affect the superior part of the vestibular nerve more frequently than the inferior part. The reason for this clinical phenomenon remains unclear. Anatomical differences may play a role, or if latent HSV-1 infection is assumed, the etiology may be due to the different distribution of the infection. To shed further light on this subject, we conducted different macro-and microanatomical studies. We also assessed the presence of HSV-1 in VG and in different sections of the VG. Our findings add new information on the macro-and microanatomy of the VG as well as the pathophysiology of vestibular neuritis. We also show that latent HSV-1 infection of VG neurons is less frequent than previously reported.KEYWORDS HSV-1 latency, human, vestibular ganglia, vestibular neuritis V estibular neuritis (VN) is a common cause of an "acute unilateral vestibulopathy." The main clinical symptoms of VN are acute onset of prolonged severe spinning vertigo with spontaneous horizontal torsional nystagmus toward the unaffected ear, postural imbalance, and nausea (1). Its annual incidence is reported to be 3.5 to 15.5 per population of 100,000 (2, 3). It is the third most common cause of peripheral vestibular

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Section: Discussionmentioning

confidence: 99%

Differential Involvement during Latent Herpes Simplex Virus 1 Infection of the Superior and Inferior Divisions of the Vestibular Ganglia: Implications for Vestibular Neuritis

Himmelein

Lindemann

Sinicina

et al. 2017

J Virol

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“…In humans and mice, HSV-1 establishes lifelong latency in the trigeminal ganglia (TG) (4,5). Reactivations of HSV-1 in the TG can lead to anterograde movement of the virus along the ophthalmic branch of the trigeminal nerve, resulting in recurrent infection of virtually all the superficial tissues of the eye, including the cornea, conjunctiva, and eyelid (6-8).…”

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confidence: 99%

Herpesvirus Entry Mediator and Ocular Herpesvirus Infection: More than Meets the Eye

Edwards

Longnecker

2017

J Virol

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As its name suggests, the host receptor herpesvirus entry mediator (HVEM) facilitates herpes simplex virus (HSV) entry through interactions with a viral envelope glycoprotein. HVEM also bridges several signaling networks, binding ligands from both tumor necrosis factor (TNF) and immunoglobulin (Ig) superfamilies with diverse, and often opposing, outcomes. While HVEM was first identified as a viral entry receptor for HSV, it is only recently that HVEM has emerged as an important host factor in immunopathogenesis of ocular HSV type 1 (HSV-1) infection. Surprisingly, HVEM exacerbates disease development in the eye independently of entry. HVEM signaling has been shown to play a variety of roles in modulating immune responses to HSV and other pathogens, and there is increasing evidence that these effects are responsible for HVEM-mediated pathogenesis in the eye. Here, we review the dual branches of HVEM function during HSV infection: entry and immunomodulation. HVEM is broadly expressed; intersects two important immunologic signaling networks; and impacts autoimmunity, infection, and inflammation. We hope that by understanding the complex range of effects mediated by this receptor, we can offer insights applicable to a wide variety of disease states.KEYWORDS HVEM, herpes simplex virus, herpes stromal keratitis H erpes simplex virus 1 (HSV-1) infects the majority of the world's population by adulthood and is responsible for the vast majority of ocular herpesvirus infections (1-3). In humans and mice, HSV-1 establishes lifelong latency in the trigeminal ganglia (TG) (4,5). Reactivations of HSV-1 in the TG can lead to anterograde movement of the virus along the ophthalmic branch of the trigeminal nerve, resulting in recurrent infection of virtually all the superficial tissues of the eye, including the cornea, conjunctiva, and eyelid (6-8). Ocular herpesvirus infections can lead to epithelial ulceration of the cornea, uveitis, and retinitis but most commonly cause herpes stromal keratitis, or HSK (9). HSK is characterized by chronic inflammation of the corneal stroma, leading to corneal thickening, opacification, scarring, and, potentially, blindness (10, 11). While reactivation accounts for the majority of human disease, most murine studies of HSK model primary infection as mice do not efficiently or reliably reactivate from latency (6).In the primary murine model of HSK, actively replicating HSV-1 in the cornea is detectable by plaque assay for up to 5 to 6 days postinfection (dpi) (9,12). Viral replication initiates HSK, as UV-inactivated or replication-deficient mutant HSV fail to induce HSK in BALB/c mice (13). However, HSK is an inflammatory disease, brought about by host infiltrates, particularly CD4 ϩ T cells and polymorphonuclear cells (PMN), that invade the murine cornea several days after replicating virus has been cleared and that persist chronically (14)(15)(16)(17)(18). A dizzying array of cytokines, chemokines, and immune cell types have been implicated in the pathogenesis of HSK, the temporal and...

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“…Herpes simplex virus (HSV) is maintained in a latent state (1) within the neural tissue of humans (2)(3)(4)(5)(6). The establishment of latency, the state of the virus, and the conditions leading to reactivation of virus are the current foci of research in this area.…”

mentioning

confidence: 99%

“…To detect HSV-2, we exposed primary rabbit kidney (PRK) cells to material from cultures frozen and thawed three times and overlaid them with 0.5% methylcellulose (20). Plaques were counted after incubation at 37°C for [3][4] After treatment with medium or with normal or immune rabbit serum, virus was assayed by plaque formation on Flow 5000 cells and overlaid with 1% agarose. § Virus was harvested from cultures treated with ara-C and HSV-2 and superinfected with 0.2 PFU of HCMV (strain AD169) 19 days after infection with HSV-2.…”

mentioning

confidence: 99%

Reactivation of herpes simplex virus type 2 from a quiescent state by human cytomegalovirus.

Colberg-Poley¹,

Isom²,

Rapp³

1979

Proc. Natl. Acad. Sci. U.S.A.

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The ability of human cytomegalovirus to stimulate replication of herpes simplex virus type 2 (HSV-2) was examined. The system used involved HSV-2-infected human embryonic lung cells under conditions (39.5-40°C) in which HSV-2 remains undetectable. Reactivation of HSV-2 was maximal and persisted for the longest duration when cultures were superinfected with 0.02 plaque-forming unit of human cytomegalovirus per cell. Infectious HSV-2 appeared 2 days after superinfection with human cytomegalovirus and ranged from 102 to 106 plaque-forming units per culture. Virus reactivated from these cultures was neutralized by rabbit immune serum produced against HSV-2. The specificity of this interaction was demonstrated by various criteria: production of HSV-2 was not observed in cultures treated with mock infecting fluid, and inactivation of human cytomegalovirus by heat, ultraviolet irradiation, or immune serum prior to superinfection eliminated its ability to induce HSV-2 replication. These results suggest that interaction between these two human herpesviruses may be of importance in herpesvirus latency in vivo.Herpes simplex virus (HSV) is maintained in a latent state (1) within the neural tissue of humans (2-6). The establishment of latency, the state of the virus, and the conditions leading to reactivation of virus are the current foci of research in this area. HSV virions and antigens in latently infected neural tissues were not detected by electron microscopy and immunofluorescence studies (1, 7). Later studies, however, demonstrated the expression of an HSV-specified enzyme, thymidine kinase (8), in the dorsal root ganglia of latently infected mice (9). This evidence suggested that the HSV genome was at least partially expressed during latency. Ganglia from latently infected mice (10) and humans (11) have also been examined by solution hybridization; HSV DNA was detected in neurons during both the acute and latent (or chronic) states (10). In contrast, virus mRNA was not detected during latent infection (10). The lack of detectable HSV mRNA contrasted strongly with the finding of HSV-specified thymidine kinase in the ganglia of latently infected mice. This paradoxical situation was resolved when in situ hybridization methods detected HSV mRNA in a small percentage (0.4-8%) of neurons in human sensory ganglia (11), substantiating that transcription of at least some regions of the HSV genome occurs during latency.We were interested in studying the reactivation of HSV type 2 (HSV-2). Frequently, under natural conditions, the human host is simultaneously a reservoir for multiple animal viruses. The interaction among these harbored viruses may be crucial to the pathological state and may be of particular significance with regard to latent virus infection. Indeed, the replication of numerous viruses has been shown to be affected by the presence of coinfecting viruses such as human adenoviruses and simian virus 40 (12, 13) or simian adenovirus SV15 (14), Marek's disease virus and avian leukosis virus (15), and Molon...

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Recovery of Herpes-Simplex Virus from Human Trigeminal Ganglions

Cited by 622 publications

References 14 publications

Differential Involvement during Latent Herpes Simplex Virus 1 Infection of the Superior and Inferior Divisions of the Vestibular Ganglia: Implications for Vestibular Neuritis

Differential Involvement during Latent Herpes Simplex Virus 1 Infection of the Superior and Inferior Divisions of the Vestibular Ganglia: Implications for Vestibular Neuritis

Herpesvirus Entry Mediator and Ocular Herpesvirus Infection: More than Meets the Eye

Reactivation of herpes simplex virus type 2 from a quiescent state by human cytomegalovirus.

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