Clonal Expansion of Hypermutated Measles Virus in a SSPE Brain

Baczko, K.; Lampe, Johanna W.; Liebert, Uwe G.; Brinckmann, Ute; Meulen, Volker ter; Pardowitz, Iancu; Budka, Herbert; Cosby, S. L.; Isserte, S.; Rima, B. K.

doi:10.1006/viro.1993.1579

Cited by 111 publications

(78 citation statements)

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“…Similar results concerning the spread of virus were found with recombinant viruses lacking the cytoplasmic tail of the fusion (F) or hemagglutinin (H) protein, suggesting that the interaction of the M protein with the cytoplasmic parts of these proteins is involved in the regulation of virus-induced cell fusion (4). Interestingly, mutations in the matrix protein and the cytoplasmic domain of the fusion protein have been found in several SSPE brains (1,5,36). To prove whether virus entry or cell-to-cell spread is indeed affected by mutation of the glycosylation site at position 200 requires further studies using single mutations at positions 195, 200, and 202 as well as positions 157 and 175 in the CAM/RB background.…”

Section: Discussionmentioning

confidence: 99%

“…These include the acute postinfectious measles encephalitis, which develops 2 to 4 weeks after infection, or the late complications, measles inclusion body encephalitis in immunocompromised patients and subacute sclerosing panencephalitis (SSPE), which develops months to years after the initial infection, based on a persistent MV infection (reviewed in reference 3). In late stages of SSPE, massive amounts of MV antigen can be detected in inclusion bodies in various neural cell types (1). SSPE is characterized by a restriction of the viral envelope protein expression as a consequence of mutational, transcriptional, and translational alterations (1,5).…”

mentioning

confidence: 99%

“…In late stages of SSPE, massive amounts of MV antigen can be detected in inclusion bodies in various neural cell types (1). SSPE is characterized by a restriction of the viral envelope protein expression as a consequence of mutational, transcriptional, and translational alterations (1,5). An additional constraint is exerted by the high concentration of antiviral antibodies present in the cerebrospinal fluid of SSPE patients.…”

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confidence: 99%

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Recombinant Measles Viruses Expressing Altered Hemagglutinin (H) Genes: Functional Separation of Mutations Determining H Antibody Escape from Neurovirulence

Moeller

Duprex

et al. 2001

J Virol

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Measles virus (MV) strain CAM/RB, which was adapted to growth in the brain of newborn rodents, is highly neurovirulent. It has been reported earlier that experimentally selected virus variants escaping from the monoclonal antibodies (MAbs) Nc32 and L77 to hemagglutinin (H) preserved their neurovirulence, whereas mutants escaping MAbs K71 and K29 were found to be strongly attenuated (U. G. Liebert et al., J. Virol. 68:1486-1493, 1994). To investigate the molecular basis of these findings, we have generated a panel of recombinant MVs expressing the H protein from CAM/RB and introduced the amino acid substitutions thought to be responsible for antibody escape and/or neurovirulence. Using these recombinant viruses, we identified the amino acid changes conferring escape from the MAbs L77 (377R3Q and 378M3K), Nc32 (388G3S), K71 (492E3K and 550S3P), and K29 (535E3G). When the corresponding recombinant viruses were tested in brains of newborn rodents, we found that the mutations mediating antibody escape did not confer differential neurovirulence. In contrast, however, replacement of two different amino acids, at positions 195G3R and 200S3N, which had been described for the escape mutant set, caused the change in neurovirulence. Thus, antibody escape and neurovirulence appear not to be associated with the same structural alterations of the MV H protein.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Recombinant Measles Viruses Expressing Altered Hemagglutinin (H) Genes: Functional Separation of Mutations Determining H Antibody Escape from Neurovirulence

Moeller

Duprex

et al. 2001

J Virol

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“…Despite the long interval between the acute infection and symptoms of SSPE, there is evidence that measles virus infection of brain occurs soon after the acute infection with subsequent spread throughout the brain. 18 Measles virus is thought to reach the brain through infection of cerebral endothelial cells, perhaps during the acute exanthema of measles when other endothelial cells are also infected. 19 Access into the brain by circulating inflammatory cells is also possible.…”

Section: Pathogenesismentioning

confidence: 99%

Subacute sclerosing panencephalitis

Garg¹

2002

Postgraduate Medical Journal

315

167

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Subacute sclerosing panencephalitis (SSPE) is a progressive neurological disorder of childhood and early adolescence. It is caused by persistent defective measles virus. Brain biopsies or postmortem histopathological examination show evidence of astrogliosis, neuronal loss, degeneration of dendrites, demyelination, neurofibrillary tangles, and infiltration of inflammatory cells. Patients usually have behavioral changes, myoclonus, dementia, visual disturbances, and pyramidal and extrapyramidal signs. The disease has a gradual progressive course leading to death within 1-3 years. The diagnosis is based upon characteristic clinical manifestations, the presence of characteristic periodic EEG discharges, and demonstration of raised antibody titre against measles in the plasma and cerebrospinal fluid. Treatment for SSPE is still undetermined. A combination of oral isoprinosine (Inosiplex) and intraventricular interferon alfa appears to be the best effective treatment. Patients responding to treatment need to receive it life long. Effective immunisation against measles is the only solution presently available to the problem of this dreaded disease.

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“…These modifications result in a predominance of A G and U C mutations (' biased hypermutations ', Cattaneo & Billeter, 1992 ;Baczko et al, 1993 ;Komase et al, 1995). In our studies, such transitions ranged between 55 and 61 %, which is quite similar to measles virus (Wong et al, 1991).…”

Section: Hfdmentioning

confidence: 99%

No evidence for quasispecies populations during persistence of the coronavirus mouse hepatitis virus JHM: sequence conservation within the surface glycoprotein gene S in Lewis rats.

Stühler¹,

Flory²,

Lassmann³

et al. 1997

Journal of General Virology

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The surface glycoprotein S (spike) of coronaviruses is believed to be an important determinant of virulence and displays extensive genetic polymorphism in cell culture isolates. This led us to consider whether the observed heterogeneity is reflected by a quasispecies distribution of mutated RNA molecules within the infected organ. Coronavirus infection of rodents is a useful model system for investigating the pathogenesis of virus-induced central nervous system (CNS) disease. Here, we investigated whether genetic changes in the S gene occurred during virus persistence in vivo. We analysed the variability of S gene sequences directly from the brain tissue of Lewis rats infected with the coronavirus mouse hepatitis virus (MHV) variant

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Clonal Expansion of Hypermutated Measles Virus in a SSPE Brain

Cited by 111 publications

References 0 publications

Recombinant Measles Viruses Expressing Altered Hemagglutinin (H) Genes: Functional Separation of Mutations Determining H Antibody Escape from Neurovirulence

Recombinant Measles Viruses Expressing Altered Hemagglutinin (H) Genes: Functional Separation of Mutations Determining H Antibody Escape from Neurovirulence

Subacute sclerosing panencephalitis

No evidence for quasispecies populations during persistence of the coronavirus mouse hepatitis virus JHM: sequence conservation within the surface glycoprotein gene S in Lewis rats.

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