Pathogenesis of Herpetic Encephalitis in Mice after Ophthalmic Inoculation

Knotts, F. Barry; Cook, Margery L.; Stevens, Jack G.

doi:10.1093/infdis/130.1.16

Cited by 108 publications

(71 citation statements)

References 16 publications

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“…Within 2 days of inoculation in the skin the virus is present in the sensory ganglia, a frequent finding now generally accepted to result from axonal transport of virus from the inoculated skin (for review, see . Ample evidence also shows that virus replicates in the neurons of the ganglia (Cook & Stevens, 1973;Dillard et al, 1972;Knotts et al, 1974). Since the nerve root samples contained mostly CNS tissue the virus probably invades the CNS via the nerve roots within 3 days of introduction into the skin.…”

Section: Discussionmentioning

confidence: 99%

Pathogenesis of Zosteriform Spread of Herpes Simplex Virus in the Mouse

Blyth

Harbour

Hill

1984

Journal of General Virology

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SUMMARYZosteriform spread of herpes simplex virus (HSV) infection occurs after primary inoculation of the skin of both outbred and inbred mice. With HSV type I strain SC 16 few outbred animals died if they were inoculated when 8 weeks old whereas up to 50 of animals died if inoculated when 4 weeks old. However, at either age, zosteriform spread of infection occurred in almost all animals as it did when 4-week-old outbred animals were inoculated with the avirulent strain KOS. Thus, control of zosteriform spread must act by different mechanisms from those controlling the encephalitis which leads to death. During replication in the epidermis virus enters axons and could first be found in sensory ganglia 2 days after inoculation of the skin. Thereafter, it was found in the nerve roots and in skin within the same dermatome but remote from the site of inoculation. When sensory nerves to this latter area were cut during the 4 days after primary inoculation lesions developing as a result of zosteriform spread were either completely inhibited or, with later section, decreased in incidence. Mortality was not affected by such nerve section. Latent infection must be established in neurons serving areas of skin remote from the inoculation site since with HSV-1 strain SC16, recrudescent lesions on the pinna could be induced by stripping the skin of the ear when the original inoculation had been in the skin of the neck. Such recrudescent disease was not demonstrated in animals infected with HSV-1 strain KOS even though this virus efficiently established latent infection in sensory ganglia.

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Section: Discussionmentioning

confidence: 99%

Pathogenesis of Zosteriform Spread of Herpes Simplex Virus in the Mouse

Blyth

Harbour

Hill

1984

Journal of General Virology

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“…There have been several reports on the dissemination of herpes simplex virus (HSV) in experimental animals (Johnson, 1963;Wildy, 1967;Cook & Stevens, 1973;Knotts et al, 1974;Oakes, 1975 a;Renis et al, 1976;Davis et al, 1979). Although the site of inoculation varied from experiment to experiment and haematogenous spread operated in some systems, the results of these experiments suggest that HSV can spread to the central nervous system (CNS) by way of peripheral nerves and regional sensory ganglia.…”

Section: Dissemination Of Herpes Simplex Virus In Nude Mice After Lntmentioning

confidence: 99%

Dissemination of Herpes Simplex Virus in Nude Mice after Intracutaneous Inoculation and Effect of Antibody on the Course of Infection

Kino

Hayashi

Hayashida

et al. 1982

Journal of General Virology

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“…Shedding of infectious virus is similarly observed in rabbit ocular models of HSV infection, both spontaneously and in response to local or systemic stimuli (16,17). In contrast, latent HSV-1 infection in the mouse seems to be more tightly regulated, and attempts to identify infectious virus or viral antigen in murine sensory ganglia after resolution of primary infection (indicative of a spontaneous reactivation localized to the sensory ganglion) have been unsuccessful (2,7,9,11,(18)(19)(20)(21)(22)(23)(24)(25)(26). These findings have led many investigators to use the mouse model to study the latent state and to assume that features of viral gene expression in this model are attributable to latency and not to spontaneous reactivation.…”

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confidence: 99%

Spontaneous molecular reactivation of herpes simplex virus type 1 latency in mice

Feldman

Ellison

Voytek

et al. 2002

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

221

210

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Infection of the mouse trigeminal ganglia (TG) is the most commonly used model for the study of herpes simplex virus type 1 (HSV-1) latency. Its popularity is caused, at least in part, by the perception that latent infection can be studied in this system in the absence of spontaneous viral reactivation. However, this perception has never been rigorously tested. To carefully study this issue, the eyes of Swiss-Webster mice were inoculated with HSV-1 (KOS), and 37-47 days later the TG were dissected, serial-sectioned, and probed for HSV-1 ICP4, thymidine kinase, glycoprotein C, and latency-associated transcript RNA by in situ hybridization. Serial sections of additional latently infected TG were probed with HSV-1-specific polyclonal antisera. Analysis of thousands of probed sections revealed abundant expression of viral transcripts, viral protein, and viral DNA replication in about 1 neuron per 10 TG tested. These same neurons were surrounded by a focal white cell infiltrate, indicating the presence of an antigenic stimulus. We conclude that productive cycle viral genes are abundantly expressed in rare neurons of latently infected murine TG and that these events are promptly recognized by an active local immune response. In the absence of detectable infectious virus in these ganglia, we propose the term ''spontaneous molecular reactivation'' to describe this ongoing process.H erpes simplex virus type 1 (HSV-1) infections of the skin or eye lead to invasion of the trigeminal ganglia (TG), where the virus follows one of two pathways (1-3). In some infected neurons, the virus replicates and destroys the cell. This lytic cycle path involves regulated viral gene expression in which immediate-early genes are required for the efficient expression of early and late genes. In other neurons, a latent infection is established in which lytic cycle genes are not expressed and infectious virus is not produced. Latent infection of neurons is characterized by the expression of the latency-associated transcripts (LAT), which are encoded in a single region of the HSV-1 genome and which accumulate to high levels in the nucleus of the host cell (4-10). In situ hybridization (ISH) studies of latently infected sensory ganglia have revealed numerous neurons expressing LAT but no other viral RNAs (4, 5, 7, 9-15). Thus, for many years a latent neuron has been defined in molecular terms as a neuron that is positive for LAT and negative for other viral RNAs.In humans, HSV-1 intermittently reactivates from the latent state, with peripheral shedding of infectious virus. Shedding of infectious virus is similarly observed in rabbit ocular models of HSV infection, both spontaneously and in response to local or systemic stimuli (16,17). In contrast, latent HSV-1 infection in the mouse seems to be more tightly regulated, and attempts to identify infectious virus or viral antigen in murine sensory ganglia after resolution of primary infection (indicative of a spontaneous reactivation localized to the sensory ganglion) have been unsuccessful (2,7,9,...

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Pathogenesis of Herpetic Encephalitis in Mice after Ophthalmic Inoculation

Cited by 108 publications

References 16 publications

Pathogenesis of Zosteriform Spread of Herpes Simplex Virus in the Mouse

Pathogenesis of Zosteriform Spread of Herpes Simplex Virus in the Mouse

Dissemination of Herpes Simplex Virus in Nude Mice after Intracutaneous Inoculation and Effect of Antibody on the Course of Infection

Spontaneous molecular reactivation of herpes simplex virus type 1 latency in mice

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