Influence of Host Factors on Neuroinvasiveness of Vesicular Stomatitis Virus

Sabin, Albert B.; Olitsky, Peter K.

doi:10.1084/jem.66.1.15

Cited by 92 publications

(28 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the present work, we examined the basis for this attenuation. Previous work has established that the pathogenesis in mice infected intranasally with VSV is due to infection of the brain that occurs via the olfactory nerve and olfactory bulb (10,17,19,28,32,36,45). The results presented here show that for the wt and all of the rearranged viruses examined, this was the mode of pathogenesis.…”

Section: Vol 77 2003 Gene Rearrangement Alters the Neuropathogenesisupporting

confidence: 57%

“…Mice have long been used to study the pathogenesis of VSV and its mutants (32,45,50). Intranasal inoculation of Swiss Webster, C57BL/6, and BALB/c mice with VSV has been well characterized, and infection results in fatal encephalitis.…”

mentioning

confidence: 99%

“…Intranasal inoculation of Swiss Webster, C57BL/6, and BALB/c mice with VSV has been well characterized, and infection results in fatal encephalitis. After intranasal administration, VSV enters the central nervous system (CNS) via the receptor neurons of the olfactory nerve, followed by invasion of the olfactory bulb and finally an acute infection of the brain (10,17,19,28,32,36,40,45). Animals given lethal doses of virus display hind-limb paralysis, meningitis, encephalitis, and death, which usually occurs within 6 to 10 days and is concurrent with a peak in viral titers in the brain.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Vesicular Stomatitis Viruses with Rearranged Genomes Have Altered Invasiveness and Neuropathogenesis in Mice

Flanagan¹,

Schoeb

Wertz³

2003

J Virol

View full text Add to dashboard Cite

Transcription of vesicular stomatitis virus is controlled by the position of a gene relative to the single 3 genomic promoter: promoter-proximal genes are transcribed at higher levels than those in more 5 distal positions. In previous work, we generated viruses having rearranged gene orders. These viruses had the promoter-proximal gene that encodes the nucleocapsid protein, N, moved to the second or fourth position in the genome in combination with the glycoprotein gene, G, moved from its usual promoter-distal fourth position to the first or third position. This resulted in three new viruses identified by the positions of the N and G genes in the gene order: G3N4, G1N4, and G1N2. The viruses G3N4 and G1N4 were attenuated for lethality in mice. In the present study, we addressed the basis of this attenuation by measuring the ability of each of the rearranged viruses to travel to and replicate in the olfactory bulb and brain following intranasal inoculation. In addition, the neuropathogenicity, serum cytokine levels, and immunoglobulin G isotype profiles in infected mice were determined. All the viruses reached the olfactory bulb and brain, but the outcomes of these infections were dramatically different. Viruses N1G4(wt) and G1N2 caused lethal encephalitis in 100% of animals within 7 days postinoculation; however, viruses G3N4 and G1N4 were cleared from the brain by 7 days postinoculation and all animals survived without apparent distress. The viruses differed in the distribution and intensity of lesions produced and the type and levels of cytokines induced. Animals inoculated with N1G4(wt) or G1N2 displayed extensive encephalitis and meningitis and had elevated levels of serum gamma interferon compared to what was seen with G3N4-or G1N4-infected mice. In contrast to what occurred with intranasal inoculation, all four viruses caused lethal encephalitis when administered by direct inoculation to the brain, a route that circumvents the majority of the host immune response, demonstrating that G3N4 and G1N4 were not deficient in their abilities to cause disease in the brain. These findings indicate that gene rearrangement and its consequent alteration of gene expression can, without any other changes, alter the viral spread and cytokine response following intranasal infection. Vesicular stomatitis virus (VSV) is the prototypic virus of the orderMononegavirales, which is composed of four families, Rhabdoviridae, Paramyxoviridae, Filoviridae, and Bornaviridae. The viruses in these families are responsible for a wide range of significant diseases in animals, fish, and plants. Viruses in all four families have a single strand of nonsegmented negativesense RNA as their genome (38). VSV is a member of the Rhabdoviridae, and its 11-kb genome has five genes encoding the five structural proteins of the virus: the nucleocapsid protein, N; the phosphoprotein, P; the matrix, M; the glycoprotein, G; and the RNA-dependent RNA polymerase, L. The order of the genes in the genome is 3Ј-N-P-M-G-L-5Ј, and the relative order of these ba...

show abstract

Section: Vol 77 2003 Gene Rearrangement Alters the Neuropathogenesisupporting

confidence: 57%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Vesicular Stomatitis Viruses with Rearranged Genomes Have Altered Invasiveness and Neuropathogenesis in Mice

Flanagan¹,

Schoeb

Wertz³

2003

J Virol

View full text Add to dashboard Cite

show abstract

“…The pathogenesis of VSV has been well described in mice (7,46,47,53,56,58,65). Mortality can be difficult to induce when delivering VSV by subcutaneous inoculation, while the mortality rate following intranasal inoculation of VSV averages 30 to 60% when a high challenge dose (e.g., Ͼ10…”

Section: Resultsmentioning

confidence: 99%

Acute Infection with Venezuelan Equine Encephalitis Virus Replicon Particles Catalyzes a Systemic Antiviral State and Protects from Lethal Virus Challenge

Konopka

Thompson

Whitmore

et al. 2009

J Virol

View full text Add to dashboard Cite

The host innate immune response provides a critical first line of defense against invading pathogens, inducing an antiviral state to impede the spread of infection. While numerous studies have documented antiviral responses within actively infected tissues, few have described the earliest innate response induced systemically by infection. Here, utilizing Venezuelan equine encephalitis virus (VEE) replicon particles (VRP) to limit infection to the initially infected cells in vivo, a rapid activation of the antiviral response was demonstrated not only within the murine draining lymph node, where replication was confined, but also within distal tissues. In the liver and brain, expression of interferon-stimulated genes was detected by 1 to 3 h following VRP footpad inoculation, reaching peak expression of >100-fold over that in mock-infected animals. Moreover, mice receiving a VRP footpad inoculation 6, 12, or 24 h prior to an otherwise lethal VEE footpad challenge were completely protected from death, including a drastic reduction in challenge virus titers. VRP pretreatment also provided protection from intranasal VEE challenge and extended the average survival time following intracranial challenge. Signaling through the interferon receptor was necessary for antiviral gene induction and protection from VEE challenge. However, VRP pretreatment failed to protect mice from a heterologous, lethal challenge with vesicular stomatitis virus, yet conferred protection following challenge with influenza virus. Collectively, these results document a rapid modulation of the host innate response within hours of infection, capable of rapidly alerting the entire animal to pathogen invasion and leading to protection from viral disease.

show abstract

“…Acute neurotropic infections are often studied in mice treated with vesicular stomatitis virus (VSV), 3 because this virus has been shown to infect neuroepithelial cells (3)(4)(5). VSV is a negativestrand RNA virus that is a member of the family rhabdoviridae.…”

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

View full text Add to dashboard Cite

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.

show abstract

Influence of Host Factors on Neuroinvasiveness of Vesicular Stomatitis Virus

Cited by 92 publications

References 2 publications

Vesicular Stomatitis Viruses with Rearranged Genomes Have Altered Invasiveness and Neuropathogenesis in Mice

Vesicular Stomatitis Viruses with Rearranged Genomes Have Altered Invasiveness and Neuropathogenesis in Mice

Acute Infection with Venezuelan Equine Encephalitis Virus Replicon Particles Catalyzes a Systemic Antiviral State and Protects from Lethal Virus Challenge

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

Contact Info

Product

Resources

About