Restriction of measles virus gene expression in acute and subacute encephalitis of Lewis rats (original) (raw)
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Virological Aspects of Measles Virus-induced Encephalomyelitis in Lewis and BN Rats
Journal of General Virology, 1987
Lewis and Brown Norway (BN) rats which are susceptible or resistant to autoimmune reactions against brain antigen, respectively, were inoculated intracerebrally with a neurotropic measles virus. Suckling rats died from a rapidly fatal acute encephalopathy (AE). With increasing age Lewis rats developed a subacute measles encephalomyelitis (SAME) whereas BN rats showed a clinically silent encephalitis (CSE). Infectious virus could occasionally be recovered from SAME animals using cocultivation techniques but not from BN rats with CSE. With monoclonal antibodies against measles virus, viral proteins were localized in brain tissue. Nucleocapsid and phosphoprotein were detected in infected brain cells of all animals with AE, SAME and CSE, whereas measles virus haemagglutinin, fusion and matrix proteins were either reduced or absent, suggesting a restricted synthesis of measles virus envelope proteins. These data suggest that the different diseases of the two rat strains are related to the immunogenetic background rather than to the replication of measles virus in the central nervous system. This animal model provides the opportunity to investigate further the events occurring during establishment of measles virus persistence in the brain, and the genetic control of associated immunological and immunopathological reactions.
Journal of General Virology, 1986
The presence of five structural proteins of measles virus in brain material obtained at autopsy from four patients with subacute sclerosing panencephalitis (SSPE) was examined by immunofluorescence employing monoclonal antibodies. In addition, the humoral immune response against measles virus antigens in serum and cerebrospinal fluid was analysed by immunoprecipitation in combination with gel electrophoresis, revealing a reduced response mainly to the matrix (M) protein. In none of the brain material were all five structural proteins simultaneously detected. Nucleocapsid protein and phosphoprotein were found in every diseased brain area, whereas haemagglutinin (H) protein was detected in two, fusion (F) protein in three and M protein only in one SSPE case. In two cases, variations in the occurrence of H and F proteins could be observed between regions displaying different degrees of neuropathological changes. No correlation was observed between the humoral immune response and the immunohistological findings. These data support the hypothesis of a restricted synthesis of measles virus proteins, in particular the envelope and M proteins, in SSPE. 0000-7226 © 1986 SGM Downloaded from www.microbiologyresearch.org by IP: 54.160.90.203
2013
Background: During 2009/10 a major measles epidemic caused by genotype B3 occurred in South Africa. Measles inclusion body encephalitis (MIBE) was diagnosed in a number of highly immuno-compromised HIV patients. The diagnosis was based on typical clinical and MRI findings and positive measles virus PCR in brain or CSF. To characterize the brain virus, nucleoprotein, matrix, fusion and haemagglutinin genes from 4 cases was compared with virus from acutely infected patients. Methods: cDNA was synthesized using random primers and viral genes were amplified by nested RT-PCR. PCR products were sequenced in the forward and reverse direction and a contig of each gene was created. Sequences were aligned with reference sequences from GenBank and other local sequences. Results: Brain virus was very similar to the South African epidemic virus. Features characteristic of persistent measles virus in the brain were absent. Mutation frequency in brain virus was similar to epidemic virus and had the same substitution preference (U to C and C to U). The virus of 2 patients had the same L454W mutation in the fusion protein.
Acta Pathologica Microbiologica Scandinavica Section B Microbiology and Immunology, 2009
Brain tissue was obtained at autopsy from a patient with subacute sclerosing panencephalitis (SSPE) and kept frozen for nine months prior to attempts at virus isolation. Mixed cultures of trypsinized brain material and Vero monkey kidney cells developed cytopathic changes resembling those associated with measles virus. The cytopathogenic effect (CPE) was transferred by cells, and in later passages, also by culture supernatants. Cells and supernatants from cultures showing CPE agglutinated monkey red cells. Haemagglutinationinhibition, immunofluorescent and neutralization experiments showed the cytopathogenic agent to be serologically similar to measles virus. Gel precipitation experiments, on the other hand, indicated differences in antigenic composition between the SSPE cultures and cultures of a vaccine (Edmonston) strain of measles virus. Ultrastructural studies revealed cytoplasmic inclusions of nucleocapsids in the SSPE cultures. The appearance and diameter of the SSPE nucleocapsids differed from those of the vaccine strain. Budding and complete viral particles were seen in both SSPE and vaccine strain cultures. I t is concluded that the SSPE agent isolated here is most probably a measles virus, but in some respects different from the Edmonston strain of measles virus.
Persistent measles virus infection of mouse neural cells lacking known human entry receptors
Neuropathology and Applied Neurobiology, 2009
Persistent measles virus infection of mouse neural cells lacking known human entry receptors Aims: Infection of the mouse central nervous system with wild type (WT) and vaccine strains of measles virus (MV) results in lack of clinical signs and limited antigen detection. It is considered that cell entry receptors for these viruses are not present on murine neural cells and infection is restricted at cell entry. Methods: To examine this hypothesis, virus antigen and caspase 3 expression (for apoptosis) was compared in primary mixed, neural cell cultures infected in vitro or prepared from mice infected intracerebrally with WT, vaccine or rodent neuroadapted viruses. Viral RNA levels were examined in mouse brain by nested and real-time reverse transcriptase polymerase chain reaction. Results: WT and vaccine strains were demonstrated for the first time to infect murine oligodendrocytes in addition to neurones despite a lack of the known MV cell receptors. Unexpectedly, the percentage of cells positive for viral antigen was higher for WT MV than neuroadapted virus in both in vitro and ex vivo cultures. In the latter the percentage of positive cells increased with time after mouse infection. Viral RNA (total and mRNA) was detected in brain for up to 20 days, while cultures were negative for caspase 3 in WT and vaccine virus infections. Conclusions: WT and vaccine MV strains can use an endogenous cell entry receptor(s) or alternative virus uptake mechanism in murine neural cells. However, viral replication occurs at a low level and is associated with limited apoptosis. WT MV mouse infection may provide a model for the initial stages of persistent MV human central nervous system infections.
Advances in Virology, 2015
Subacute Sclerosing Panencephalitis (SSPE), a rare lethal disease of children and young adults due to persistence of measles virus (MeV) in the brain, is caused by wild type (wt) MeV. Why MeV vaccine strains never cause SSPE is completely unknown. Hypothesizing that this phenotypic difference could potentially be represented by a molecular marker, we compared glycoprotein and matrix (M) genes from SSPE cases with those from the Moraten vaccine strain, searching for differential structural motifs. We observed that all known SSPE viruses have residues P64, E89, and A209 (PEA) in their M proteins whereas the equivalent residues for vaccine strains are either S64, K89, and T209 (SKT) as in Moraten or PKT. Through the construction of MeV recombinants, we have obtained evidence that the wt MeV-M protein PEA motif, in particular A209, is linked to increased viral spread. Importantly, for the 10 wt genotypes (of 23) that have had their M proteins sequenced, 9 have the PEA motif, the excepti...
The P gene of rodent brain-adapted measles virus plays a critical role in neurovirulence
The Journal of general virology, 2017
In rare cases, measles virus (MV) in children leads to fatal neurological complications such as primary measles encephalitis, post-acute measles encephalitis, subacute sclerosing panencephalitis and measles inclusion-body encephalitis. To investigate the pathogenesis of MV-induced encephalitis, rodent brain-adapted MV strains CAM/RB and CAMR40 were generated. These strains acquired mutations to adapt to the rodent brain during 40 passages in rat brain. However, it is still unknown which genes confer the neurovirulence of MV. We previously established a rescue system for recombinant MVs possessing the backbone of wild-type strain HL, an avirulent strain in mice. In the present study, to identify the genes in CAMR40 that elicit neurovirulence, we generated chimeric recombinant MVs based on strain HL. As a result, recombinant wild-type MV in which the haemagglutinin (H) gene was substituted with that of CAMR40 caused a non-lethal mild disease in mice, while additional substitution of t...
Journal of General Virology, 1991
Lewis rats were immunized with recombinant vaccinia virus (VV) expressing the nucleocapsid (N), phospho (P), matrix (M), fusion (F), and haemagglutinin (H) proteins of measles virus (MV). Animals developed humoral as well as cell-mediated immune (CMI) responses to the corresponding MV proteins. Rats immunized with recombinants VVN, VVF or VVH survived a MV challenge infection whereas VVP-and VVM-immunized rats were only partially protected. In vivo depletion of CD8 ÷ T lymphocytes did not prevent the protective effect of the N, F or H protein-specific CMI response in rats. VVH and VVF immunization induced neutralizing antibodies, but no such antibodies were detected after VVN immunization. Further investigation of the temporal occurrence of the antiviral antibodies indicated that the observed protection provided by VVN and VVF immunization depends on CD4 ÷ N-or F-specific T cells in the absence of neutralizing antibodies and CD8 ÷ T cells. A role for neutralizing antibodies induced by VVH cannot be ruled out. 0001-0323 © 1991 SGM