Age-dependent resistance to murine retrovirus-induced spongiform neurodegeneration results from central nervous system-specific restriction of virus replication

Czub, Markus; Czub, Stefanie; McAtee, Frank J.; Portis, John L.

doi:10.1128/jvi.65.5.2539-2544.1991

Cited by 55 publications

(45 citation statements)

References 24 publications

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“…Mice were inoculated intraperitoneally as neonates (1 to 2 days postnatally) with 30 l of the virus stocks containing 6 ϫ 10 4 to 9 ϫ 10 4 focus-forming units of infectivity. Virus stocks were assayed for infectivity by using a focal immunoassay described previously (9). At 12 to 14 days postinoculation, mice were killed by exsanguination under methoxyflurane inhalation anesthesia and spleens were removed for analysis (see below).…”

Section: Methodsmentioning

confidence: 99%

Characterization of glycosylated Gag expressed by a neurovirulent murine leukemia virus: identification of differences in processing in vitro and in vivo

Fujisawa

McAtee

Zirbel

et al. 1997

J Virol

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The neuroinvasiveness of a chimeric murine retrovirus, CasFr KP (KP), is dependent on the expression of glycosylated Gag (gp85 gag). This viral protein is the product of alternate translation initiation 88 codons upstream of and in frame with the initiation codon of pr65 gag , the precursor of the viral core proteins. Although expression of glycosylated Gag affects virus spread in the spleen, it appears not to affect virus spread in vitro in fibroblast cell lines (J. L. Portis et al., J. Virol. 68:3879-3887, 1994). The differential effects of this protein in vitro and in vivo have not been explained, and its function is unknown. We have here compared the in vitro processing of this molecule with that expressed in spleens of infected mice. In vitro, gp85 gag was cleaved near the middle of the molecule, releasing the C-terminal half (containing capsid and nucleocapsid domains of pr65 gag) as a secreted glycoprotein. The N-terminal half of the protein was associated with the plasma membrane as a ϳ55-kDa glycoprotein bearing the matrix domain of pr65 gag as well as the N-terminal 88 residue L domain. This processing scheme was also observed in vivo, although two differences were seen. There were differences in N-linked glycosylation of the secreted form of the protein expressed in the spleen. In addition, whereas the membrane-associated species assumed the orientation of a type II integral membrane protein (N cyto C exo) in fibroblasts in vitro, a subpopulation of spleen cells was detected in which the N terminus of the protein was exposed at the cell surface. These results suggest that the differential effects of glycosylated Gag expression in vivo and in vitro may be related to differences in posttranslational processing of the protein.

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Section: Methodsmentioning

confidence: 99%

Characterization of glycosylated Gag expressed by a neurovirulent murine leukemia virus: identification of differences in processing in vitro and in vivo

Fujisawa

McAtee

Zirbel

et al. 1997

J Virol

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“…The age of the mouse at the time of infection is also critical in determining these kinetics. Beginning approximately at five days, neonatal mice become resistant to CNS infection, and by ten days this resistance is complete (7). Thus, virus infection of the CNS must be accom-…”

Section: The Model and T H E Consensusmentioning

confidence: 99%

The Pathogenesis of Murine Retroviral Infection of the Central Nervous System

Wiley

Gardner

1993

Brain Pathology

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Several decades have lapsed since the original description of retroviral infection of the central nervous system (CNS) appeared. With the recent arrival of the autoimmune deficiency syndrome (AIDS) epidemic and the associated human retroviral encephalitis, interest in murine models has been rekindled. In most of the published studies, susceptible mouse strains are infected as neonates with molecularly cloned type-C retroviruses. In most models, a spongiform encephalopathy follows an early CNS endothelial cell infection. The subsequent pathogenesis of this encephalopathy is unknown. In some models neuronal and glial infection is seen, while in others only non-neuroglial elements are infected. This variation can be traced to differences in strains of mice and viruses in addition to differences in assays. The different models offer fertile experimental ground to decipher the role of direct versus indirect neuroglial damage. Reconciliation of these various models where the final neuropathology appears so similar, may be the key to understanding their pathogenesis.

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“…In contrast to neonatally inoculated mice, when FrCas E is inoculated into mice at P10, the virus replicates in the periphery but the mice do not develop neurological disease. This age-dependent resistance is a consequence of an intrinsic central nervous system (CNS)-specific restriction of virus infection which develops as a function of as yet unknown, postnatal developmental factors (12,13). In these mice, there is neither immunohistochemical evidence of virus expression in the CNS nor any evidence of spongiform degeneration (12,44).…”

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confidence: 99%

Induction of focal spongiform neurodegeneration in developmentally resistant mice by implantation of murine retrovirus-infected microglia

Lynch

Robertson

Portis

1995

J Virol

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FrCas E is a highly neurovirulent murine leukemia virus which causes a noninflammatory spongiform neurodegenerative disease after neonatal inoculation. The central nervous system (CNS) infection is widespread, involving several different cell types, whereas the lesions are localized to motor areas of the brain and spinal cord. Inoculation of FrCas E at 10 days of age (P10) results in viremia, but infection of the CNS is restricted and neurological disease is not observed (M.

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Age-dependent resistance to murine retrovirus-induced spongiform neurodegeneration results from central nervous system-specific restriction of virus replication

Cited by 55 publications

References 24 publications

Characterization of glycosylated Gag expressed by a neurovirulent murine leukemia virus: identification of differences in processing in vitro and in vivo

Characterization of glycosylated Gag expressed by a neurovirulent murine leukemia virus: identification of differences in processing in vitro and in vivo

The Pathogenesis of Murine Retroviral Infection of the Central Nervous System

Induction of focal spongiform neurodegeneration in developmentally resistant mice by implantation of murine retrovirus-infected microglia

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