Defective Measles Virus in Human Subacute Sclerosing Panencephalitis Brain

Sidhu, M. S.; Crowley, Joan C.; Löwenthal, A.; Karcher, D.; Menonna, Joseph; Cook, Stuart D.; Udem, Stephen A.; Dowling, Peter C.

doi:10.1006/viro.1994.1384

Cited by 73 publications

(46 citation statements)

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“…However, it is thought that MV enters by the respiratory route, initially infecting epithelial cells in the respiratory tract (12). Furthermore, there have been reports that in addition to infecting cells of the immune system, MV also infects endothelial (11,15,16,21,24), epithelial (21,24,44), and neuronal cells (3,24,40) in vivo, none of which have been shown to express SLAM. One explanation for this paradox is that all of these cells express low levels of SLAM sufficient for MV infection.…”

Section: Discussionmentioning

confidence: 99%

“…We have also reported that viruses obtained from clinical specimens (throat swabs of measles patients) use SLAM but not CD46 as a receptor (28). Previous histopathological studies in vivo, however, have revealed that in addition to infecting SLAM-positive cells of the immune system, MV also infects endothelial (11, 15, 16, 21, 24), epithelial (21, 24, 44), and neuronal cells (3,24,40), none of which have been shown to express SLAM (7, 41). Thus, the in vivo receptor usage of MV remains to be determined.…”

Section: Ic323-egfp Infection Of Slam-negative Cells This Infection mentioning

confidence: 99%

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SLAM (CD150)-Independent Measles Virus Entry as Revealed by Recombinant Virus Expressing Green Fluorescent Protein

Hashimoto

Ono

Tatsuo

et al. 2002

J Virol

199

201

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IC323-EGFP infection of SLAM-negative cells. This infection occurred under conditions in which entry via endocytosis was inhibited. These results indicate that MV can infect a variety of cells, albeit with a low efficiency, by using an as yet unidentified receptor(s) other than SLAM or CD46, in part explaining the observed MV infection of SLAM-negative cells in vivo.Measles virus (MV) is an enveloped virus of the Morbillivirus genus in the Paramyxoviridae family and has a linear, nonsegmented, negative-strand RNA genome with two envelope glycoproteins, the hemagglutinin (H) and fusion (F) proteins (12). Despite the development of effective live vaccines, measles remains a significant cause of infant mortality worldwide, mainly due to secondary infections caused by MV-induced immunosuppression (12).Vaccine strains of MV such as the Edmonston strain use human CD46 as a cellular receptor (9, 25). Since CD46 is expressed on all nucleated human cells (19), vaccine strains of MV can infect almost any human cell line. In contrast, wildtype strains of MV isolated in the marmoset B-cell line B95a or human B-cell lines are usually unable to use CD46 as a receptor (6,13,17,18,36,37,46,47). Recently, we have demonstrated that signaling lymphocyte activation molecule (SLAM; also known as CD150) acts as a cellular receptor for both vaccine and wild-type strains of MV (48). SLAM is a costimulatory molecule in lymphocyte activation (7), and its expression is restricted to activated T and B lymphocytes, immature thymocytes (7, 41), mature dendritic cells (26), and activated monocytes (23), nicely explaining the tropism of MV as well as the lymphopenia and immunosuppression observed in MV infection. We have also reported that viruses obtained from clinical specimens (throat swabs of measles patients) use SLAM but not CD46 as a receptor (28). Previous histopathological studies in vivo, however, have revealed that in addition to infecting SLAM-positive cells of the immune system, MV also infects endothelial (11, 15, 16, 21, 24), epithelial (21, 24, 44), and neuronal cells (3,24,40), none of which have been shown to express SLAM (7, 41). Thus, the in vivo receptor usage of MV remains to be determined.Reverse genetics technology has enabled us to study a number of important problems concerning virus replication and pathogenesis. As for MV, the rescue of the Edmonston strain from cloned DNA was developed in 1995 (32), providing us with many insights into MV biology (10,30,31,35,49,50). However, since the vaccine strain does not exhibit pathogenicity in experimentally infected monkeys (1, 17), results obtained with it may not be applicable to clinical problems in vivo. Recently, Takeda et al. have successfully developed the rescue system of a wild-type MV strain that could reproduce the natural course of MV pathology in monkeys, opening the way to molecularly dissecting the pathogenesis of MV infection at the level of viral genomes (45).In this study, we examined MV entry into SLAM-negative cells. To facilitate the analysis, we recove...

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Section: Discussionmentioning

confidence: 99%

Section: Ic323-egfp Infection Of Slam-negative Cells This Infection mentioning

confidence: 99%

SLAM (CD150)-Independent Measles Virus Entry as Revealed by Recombinant Virus Expressing Green Fluorescent Protein

Hashimoto

Ono

Tatsuo

et al. 2002

J Virol

199

201

View full text Add to dashboard Cite

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“…We modified the RT-PCR amplification protocol of Calain et al (1992), where the copy-back DI RNAs were amplified using two set of MV primers (for 5' copy-back DIs, JM396; 5'-TATAAGCTTACCAGACAAAGCTGGGAATAGAAACTTCG-3'/JM403; 5'-CGAAGATATTCTGGTGTAAGTCTAGTA-3', and for standard genome, JM396/JM402; 5'-TTTATCCAGAATCTCAARTCCGG-3') (Sidhu et al, 1994;Whistler et al, 1996). Viral RNA from the culture supernatant was extracted with QIAamp Viral RNA Mini kit (Qiagen).…”

Section: Rt-pcr Amplification Of Cdna From 5' Copy-back DI Rnasmentioning

confidence: 99%

Strain-to-strain difference of V protein of measles virus affects MDA5-mediated IFN-β-inducing potential

Takaki

Watanabe

Shingai

et al. 2011

Molecular Immunology

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Laboratory-adapted and vaccine strains of measles virus (MV) induce type I interferon (IFN) in infected cells to a far greater extent than wild-type strains. We investigated the mechanisms for this differential type I IFN production in cells infected with representative MV strains. The overexpression of the wild-type V protein suppressed melanoma differentiation-associated gene 5 (MDA5)-induced IFN-E promoter activity, while this was not seen in A549 cells expressing CD150 infected with the V protein of the vaccine strain. The V proteins of the wild-type also suppressed poly I:C-induced IFN regulatory factor 3 (IRF-3) dimerization. The V proteins of the wild-type and vaccine strain did not affect retinoic acid-inducible gene 1 (RIG-I)-or toll-IL-1R homology domain-containing adaptor molecule 1 (TICAM-1)-induced IFN-E promoter activation. We identified an amino acid substitution of the cysteine residue at position 272 (which is conserved among paramyxoviruses) to an arginine residue in the V protein of the vaccine strain. Only the V protein possessing the 272C residue binds to MDA5. The mutation introduced into the wild-type V protein (C272R) was unable to suppress MDA5-induced IRF-3 nuclear translocation and IFN-E promoter activation as seen in the V proteins of the vaccine strain, whereas the mutation introduced in the vaccine strain V protein (R272C) was able to inhibit MDA5-induced IRF-3 and IFN-E promoter activation. The other 6 residues of the vaccine strain V sequence inconsistent with the authentic sequence of the wild-type V protein barely affected the IRF-3 nuclear translocation. These data suggested that the structural difference of vaccine MV V protein hampers MDA5 blockade and acts as a nidus for the spread/amplification of type I IFN induction. Ultimately, measles vaccine strains have two modes of IFN-E-induction for their attenuation: V protein mutation and production of defective interference (DI) RNA.3

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“…18 24 Numerous alterations in M protein have been described in SSPE because of extensive point mutations in viral genome, possibly resulting in persistent viral infection. [25][26][27][28][29][30] The type II transmembrane protein H mediates virus cell attachment by binding to the cell surface protein CD46 (it is a measles virus receptor protein, which is, in fact, a complement regulating protein with isoforms present on neurons), 31 and is an essential cofactor for fusion. 32 Changes in the H and F proteins can also be associated with persistent infection, with M protein remaining relatively unaffected.…”

Section: Pathogenesismentioning

confidence: 99%

Subacute sclerosing panencephalitis

Garg¹

2002

Postgraduate Medical Journal

318

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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Defective Measles Virus in Human Subacute Sclerosing Panencephalitis Brain

Cited by 73 publications

References 0 publications

SLAM (CD150)-Independent Measles Virus Entry as Revealed by Recombinant Virus Expressing Green Fluorescent Protein

SLAM (CD150)-Independent Measles Virus Entry as Revealed by Recombinant Virus Expressing Green Fluorescent Protein

Strain-to-strain difference of V protein of measles virus affects MDA5-mediated IFN-β-inducing potential

Subacute sclerosing panencephalitis

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