Distribution of vesicular stomatitis virus proteins in the brain of BALB/c mice following intranasal inoculation: an immunohistochemical analysis

Huneycutt, Brandon S.; Plakhov, Ilia V.; Shusterman, Zak; Bartido, Shirley; Huang, Alice S.; Reiss, Carol Shoshkes; Aoki, Chiye

doi:10.1016/0006-8993(94)91426-5

Cited by 87 publications

(103 citation statements)

References 49 publications

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“…Histology and severity of disease. Lesions in mice inoculated with N1G4(wt) were as expected based on the results of previous studies (19,32) and were characterized by the accumulation of lymphocytes in the leptomeninges and around vessels within the brain, accompanied by areas of necrosis and the accumulation of neutrophils (Fig. 3B and F).…”

Section: Viral Replication In Micesupporting

confidence: 86%

“…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.…”

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confidence: 99%

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

Flanagan¹,

Schoeb

Wertz³

2003

J Virol

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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...

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Section: Viral Replication In Micesupporting

confidence: 86%

mentioning

confidence: 99%

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

Flanagan¹,

Schoeb

Wertz³

2003

J Virol

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“…(Huneycutt et al, 1994;Sabin and Olitsky, 1938). Immunocompetent mice exhibit high morbidity and mortality at low doses of virus, succumbing to infection between 6 and 11 days post infection (p.i.).…”

Section: Introductionmentioning

confidence: 99%

“…Immunocompetent mice exhibit high morbidity and mortality at low doses of virus, succumbing to infection between 6 and 11 days post infection (p.i.). In contrast, inoculation of immunocompetent mice with high doses of VSV by the intramuscular, subcutaneous, or intraperitoneal routes generally leads to limited viral replication and no apparent disease (Reiss and Aoki, 1994). Similarly, intravenous (i.v.)…”

Section: Introductionmentioning

confidence: 99%

Peripheral, but not central nervous system, type I interferon expression in mice in response to intranasal vesicular stomatitis virus infection

2007

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Type I interferon (IFN) is critical for resistance of mice to infection with vesicular stomatitis virus (VSV). Wild type (wt) VSV infection did not induce type I IFN production in vitro or in the central nervous system (CNS) of mice; however IFN-β was detected in lungs, spleen, and serum within 24 h. The M protein mutant VSV, T1026R1 (also referred to as M51R), induced type I IFN production in vitro and in the CNS, with poor expression in spleens. In addition, VSV T1026R1 was not pathogenic to mice after intranasal infection, illustrating the importance of IFN in controlling VSV replication in the CNS. Experiments with chemical sympathectomy, sRAGE, and neutralizing antibody to VSV were performed to investigate the mechanism(s) utilized for induction of peripheral IFN; neither sRAGE infusion nor chemical sympathectomy had an effect on peripheral IFN production. In contrast, administration of neutralizing antibody (Ab) readily blocked the response. Infectious VSV was transiently present in lungs and spleens at 24 h post infection. The results are consistent with VSV traffic from the olfactory neuroepithelium to peripheral lymphoid organs hematogenously or via lymphatic circulation. These results suggest that VSV replicates to high titers in the brains of mice because of the lack of IFN production in the CNS after intranasal VSV infection. In contrast, replication of VSV in peripheral organs is controlled by the production of large amounts of IFN.Address correpondence to

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“…We inoculated these recombinant viruses into pigs and analyzed their pathogenicities as measured by the severity of the induced lesions and by virus replication. The results were compared to those obtained after intranasal inoculation of mice, a well-established laboratory model for VSV pathogenesis (21,36,38,40,48,55). Our observations demonstrated the involvement of the G glycoprotein in the pathogenesis of VSV in swine and highlighted the differences between laboratory mice and natural hosts following VSV infection.…”

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confidence: 99%

Vesicular Stomatitis Virus Glycoprotein Is a Determinant of Pathogenesis in Swine, a Natural Host

Martı́nez

Rodrı́guez

Jiménez

et al. 2003

J Virol

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There are two major serotypes of vesicular stomatitis virus (VSV), Indiana (VSIV) and New Jersey (VSNJV). We recovered recombinant VSIVs from engineered cDNAs that contained either (i) one copy of the VSIV G gene (VSIV-GI); (ii) two copies of the G gene, one from each serotype (VSIV-GNJGI); or (iii) a single copy of the GNJ gene instead of the GI gene (VSIV-GNJ). The recombinant viruses expressed the appropriate glycoproteins, incorporated them into virions, and were neutralized by antibodies specific for VSIV (VSIV-GI), VSNJV (VSIV-GNJ), or both (VSIV-GNJGI), according to the glycoprotein(s) they expressed. All recombinant viruses grew to similar titers in cell culture. In mice, VSIV-GNJ and VSIV-GNJGI were attenuated. However, in swine, a natural host for VSV, the GNJ glycoprotein-containing viruses caused more severe lesions and replicated to higher titers than the parental virus, VSIV-GI. These observations implicate the glycoprotein as a determinant of VSV virulence in a natural host and emphasize the differences in VSV pathogenesis between mice and swine

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Distribution of vesicular stomatitis virus proteins in the brain of BALB/c mice following intranasal inoculation: an immunohistochemical analysis

Cited by 87 publications

References 49 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

Peripheral, but not central nervous system, type I interferon expression in mice in response to intranasal vesicular stomatitis virus infection

Vesicular Stomatitis Virus Glycoprotein Is a Determinant of Pathogenesis in Swine, a Natural Host

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