Vaccinia virus meningitis in mice after intracerebral inoculation

Ginsberg, Arthur; Johnson, Kenneth P.

doi:10.1128/iai.13.4.1221-1227.1976

Cited by 17 publications

(5 citation statements)

References 19 publications

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“…Rapid virus replication is associated with the lysis of the host cell. Similar findings have been reported by others (3,5).…”

Section: Discussionsupporting

confidence: 93%

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Vaccinia virus infection of the central nervous system in X-irradiated mice

Simon¹,

Werner²

1979

Infect Immun

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The effect of X-irradiation on experimental vaccinia infection of BALB/c mice was studied. As compared with nonirradiated controls, the X-irradiated animals exhibited (i) a time lag in virus replication (delayed, but protracted replication); (ii) a delayed and repressed immune response: (iii) more severe acute cytocidal infection of leptomeninges, choroid plexus, ependyma, and vessels, with extensive damage to the brain-barrier system; and (iv) noncytocidal, latent infection of glial cells and neurons. Several animals developed acute or subacute demyelination disease, resembling experimental allergic encephalomyelitis or postinfectious encephalomyelitis.

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“…Rapid virus replication is associated with the lysis of the host cell. Similar findings have been reported by others (3,5).…”

Section: Discussionsupporting

confidence: 93%

“…No virus was found on day 13. In the nonirradiated controls (A) the virus was detected on day 3, reaching a maximum on day 5 on July 15, 2020 by guest http://iai.asm.org/ Downloaded from detected on day 9. The peak titers in both groups did not differ significantly.…”

Section: Resultsmentioning

confidence: 99%

Vaccinia virus infection of the central nervous system in X-irradiated mice

Simon¹,

Werner²

1979

Infect Immun

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“…Most mice infected with vaccinia virus at a high multiplicity of infection die several days after IC inoculation, exhibiting no marked cell accumulation. On the other hand, mice infected with a low multiplicity of infection recover from the infection, and a large number of mononuclear cells are accumulated in the meningeal area (5).…”

Section: Discussionmentioning

confidence: 99%

Meningeal exudate cells in vaccinia meningitis of mice: role of local T cells

Morishima¹,

Hayashi²

1978

Infect Immun

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Intracerebral inoculation of vaccinia virus into adult DDD mice produced intensive meningitis several days after infection. The inflammatory reaction could be quantitated by counting cells obtained from this inflammatory lesion. The local virus titer increased until day 5 and subsequently decreased rapidly with time. Concomitant with this titer decrease, numerous meningeal exudate cells appeared in the lesion. The cytotoxic activity of these cells against vaccinia virusinfected cells was studied after removal of glass-adherent cells. The results showed that these meningeal exudate cells possessed cytotoxic activity against the virusinfected cells and moreover inhibited plaque formation by vaccinia virus. The magnitude of this activity was much larger than that of spleen cells obtained from the same animals. After treatment with antithymocyte serum, or with antitheta serum plus complement, the meningeal cells lost their inhibitory activity, suggesting that the cells which exerted the effect were mainly T lymphocytes. The meningeal exudate cells obtained on day 7 postinfection were further characterized. A greater part, approximately 80%, of the cell population was composed of theta-positive cells. Less than 1% carried immunoglobulin, 7% possessed neither theta antigen nor immunoglobulin on the surface, and 12% represented glassadherent cells.

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“…Whether the neurovirulence capacity of VACV-WR involves not only the ability to attenuate the immune response in the brain as shown here but also additional, non-immune, virulence mechanisms, mainly within the brain, remains elusive. Intracranial infection of mice with poxviruses has been previously used to evaluate the importance of various proteins (i.e., N1L [17]), pathogenesis of different orthopoxviruses [20], and to characterize the cellular immune response following sublethal infection [18]. Viral proteins which contribute to the virulence of VACV-WR through modulation of the host immune response include C4, N2, B13, B14, 169, C6, N1, and F1 [29,30,31,32,33,34,35].…”

Section: Discussionmentioning

confidence: 99%

“…and followed by kinetic multi parametric analysis of both viral and host response to the infection. Intracranial infection can be used to address questions like virulence/attenuation and neuroadaptation and has also been used to demonstrate the attenuation of the vaccine strains [16,17,18,19,20,21]. Direct i.c.…”

Section: Introductionmentioning

confidence: 99%

Differential Response Following Infection of Mouse CNS with Virulent and Attenuated Vaccinia Virus Strains

et al. 2019

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Viral infections of the central nervous system (CNS) lead to a broad range of pathologies. CNS infections with Orthopox viruses have been mainly documented as an adverse reaction to smallpox vaccination with vaccinia virus. To date, there is insufficient data regarding the mechanisms underlying pathological viral replication or viral clearance. Therefore, informed risk assessment of vaccine adverse reactions or outcome prediction is limited. This work applied a model of viral infection of the CNS, comparing neurovirulent with attenuated strains. We followed various parameters along the disease and correlated viral load, morbidity, and mortality with tissue integrity, innate and adaptive immune response and functionality of the blood–brain barrier. Combining these data with whole brain RNA-seq analysis performed at different time points indicated that neurovirulence is associated with host immune silencing followed by induction of tissue damage-specific pathways. In contrast, brain infection with attenuated strains resulted in rapid and robust induction of innate and adaptive protective immunity, followed by viral clearance and recovery. This study significantly improves our understanding of the mechanisms and processes determining the consequence of viral CNS infection and highlights potential biomarkers associated with such outcomes.

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Vaccinia virus meningitis in mice after intracerebral inoculation

Cited by 17 publications

References 19 publications

Vaccinia virus infection of the central nervous system in X-irradiated mice

Vaccinia virus infection of the central nervous system in X-irradiated mice

Meningeal exudate cells in vaccinia meningitis of mice: role of local T cells

Differential Response Following Infection of Mouse CNS with Virulent and Attenuated Vaccinia Virus Strains

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