Characterization of measles virus strains causing SSPE: A study of 11 cases

Jin, Li; Beard, Stuart; Hunjan, Rashpal; Brown, David; Miller, Elizbeth

doi:10.1080/13550280290100752

Cited by 74 publications

(49 citation statements)

References 42 publications

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“…Furthermore, the sequences are typically related not to the currently circulating wild-type viruses, but to those in circulation when the individual developed the acute infection as an infant. These observations confirm that SSPE represents the prime example for the long-term persistence of an RNA virus in the human and that it is not caused by MV reinfection [78,79] (P Rota, personal communication). This is also consistent with the fact that an acute MV infection confers life-long immunity to the individual.…”

Section: The Defective Nature Of Virus In Sspe and Mibe Brainssupporting

confidence: 66%

Morbilliviruses and human disease

Rima

Duprex

2005

The Journal of Pathology

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Morbilliviruses are a group of viruses that belong to the family Paramyxoviridae. The most instantly recognizable member is measles virus (MV) and individuals acutely infected with the virus exhibit a wide range of clinical symptoms ranging from a characteristic mild selflimiting infection to death. Canine distemper virus (CDV) and rinderpest virus (RPV) cause a similar but distinctive pathology in dogs and cattle, respectively, and these, alongside experimental MV infection of primates, have been useful models for MV pathogenesis. Traditionally, viruses were identified because a distinctive disease was observed in man or animals; an infectious agent was subsequently isolated, cultured, and this could be used to recapitulate the disease in an experimentally infected host. Thus, satisfying Koch's postulates has been the norm. More recently, particularly due to the advent of exceedingly sensitive molecular biological assays, many researchers have looked for infectious agents in disease conditions for which a viral aetiology has not been previously established. For these cases, the modified Koch's postulates of Bradford Hill have been developed as criteria to link a virus to a specific disease. Only in a few cases have these conditions been fulfilled. Therefore, many viruses have over the years been definitely and tentatively linked to human diseases and in this respect the morbilliviruses are no different. In this review, human diseases associated with morbillivirus infection have been grouped into three broad categories: (1) those which are definitely caused by the infection; (2) those which may be exacerbated or facilitated by an infection; and (3) those which currently have limited, weak, unsubstantiated or no credible scientific evidence to support any link to a morbillivirus. Thus, an attempt has been made to clarify the published data and separate human diseases actually linked to morbilliviruses from those that are merely anecdotally associated.

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Section: The Defective Nature Of Virus In Sspe and Mibe Brainssupporting

confidence: 66%

Morbilliviruses and human disease

Rima

Duprex

2005

The Journal of Pathology

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“…4 are from a different SSPE brain than the brain-derived SSPE rAbs and differ from the Edmonston strain at 11 amino acid positions within this region (data not shown). Furthermore, the putative rAb 1 N protein epitope (AHLSTDTPLD) expressed by T7 clones A and B shares only weak homology (indicated in bold) to peptide 1-R (ARLLIG TSPD), while the sequence of this region in N proteins (AHL PIGTSLD) from other SSPE brains is more homologous to peptide 1-R (17). The homology of the N proteins from these strains identified this region of the N protein as the probable rAb 1 epitope.…”

Section: Discussionmentioning

confidence: 99%

Screening Random Peptide Libraries with Subacute Sclerosing PanencephalitisBrain-Derived Recombinant Antibodies Identifies Multiple Epitopes in the C-Terminal Region of the Measles Virus Nucleocapsid Protein

Owens¹,

Shearer²,

Yu³

et al. 2006

J Virol

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Infectious and inflammatory diseases of the CNS are often characterized by a robust B-cell response that manifests as increased intrathecal immunoglobulin G (IgG) synthesis and the presence of oligoclonal bands. We previously used laser capture microdissection and single-cell PCR to analyze the IgG variable regions of plasma cells from the brain of a patient with subacute sclerosing panencephalitis (SSPE). Five of eight human IgG1 recombinant antibodies (rAbs) derived from SSPE brain plasma cell clones recognized the measles virus (MV) nucleocapsid protein, confirming that the antibody response in SSPE targets primarily the agent causing disease. In this study, as part of our work on antigen identification, we used four rAbs to probe a random phage-displayed peptide library to determine if epitopes within the MV nucleocapsid protein could be identified with SSPE brain rAbs. All four of the SSPE rAbs enriched phage-displayed peptide sequences that reacted specifically to their panning rAb by enzyme-linked immunosorbent assay. BLASTP searches of the NCBI protein database revealed clear homologies in three peptides and different amino acid stretches within the 65 C-terminal amino acids of the MV nucleocapsid protein. The specificities of SSPE rAbs to these regions of the MV nucleocapsid protein were confirmed by binding to synthetic peptides or to short cDNA expression products. These results indicate the feasibility of using peptide screening for antigen discovery in central nervous system inflammatory diseases of unknown etiology, such as multiple sclerosis, neurosarcoidosis, or Behcet's syndrome.Panning of phage-displayed random peptide libraries allows an unbiased selection of antibody epitopes/mimotopes without preconceptions about the nature of the target antigens (reviewed in reference 23). In central nervous system (CNS) inflammatory diseases, where access to active diseased tissue is limited or where the levels of tissue antigen may be extremely low, phage peptide panning provides an alternative and sensitive avenue for antigen identification. Panning of phage-displayed random peptide libraries has successfully identified rheumatoid factor-specific mimotopes (22) and allergen mimotopes (19) and has mapped both linear and discontinuous viral epitopes recognized by antibodies specific for various infectious agents (5,10,11,16,20).Infectious and inflammatory diseases of the CNS are often characterized by increased intrathecal immunoglobulin G (IgG) synthesis that is seen as discrete bands of oligoclonal IgG when cerebrospinal fluid (CSF) or brain IgG is separated by isoelectric focusing. In CNS infectious diseases, such as subacute sclerosing panencephalitis (SSPE), neurosyphilis, mumps meningitis, progressive rubella panencephalitis, cryptococcal meningitis, and varicella zoster virus vasculitis, the oligoclonal IgG is directed largely against the infectious agent that causes the disease (reviewed in reference 12). Increased CNS IgG synthesis is accompanied by an elevated number of CD19 ϩ B cells and the app...

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“…some SSPE virus strains have mutations that drastically alter the structure of the M protein, due to the lack of the normal initiation codon with the usage of an alternative initiation codon and alternative termination codons (3,14,20). Our study has revealed that the M protein of SSPE-Kobe-1 has the authentic N-and C-termini.…”

Section: Deduced Amino Acid Sequence Analysis Of the Sspe Virus Proteinsmentioning

confidence: 83%

“…The mutation rates of each viral protein-coding region range from 0.8% (L coding region) to 1.6% (H coding region), with the overall mutation rate being 1.2% (194/15,894) ( Table 2). It has been reported that the M gene of SSPE virus possesses a considerably large number of mutations (usually more than 30), the majority of which are the U-to-C biased hypermutation (2,9,20,45). We found that the mutation rate of the M coding region of SSPE-Kobe-1 was only 1.2% (12/1,008).…”

Section: Nucleotide Sequence and Phylogenetic Analyses Of The Sspe VImentioning

confidence: 99%

Full‐Length Sequence Analysis of Subacute Sclerosing Panencephalitis (SSPE) Virus, a Mutant of Measles Virus, Isolated from Brain Tissues of a Patient Shortly after Onset of SSPE

Hotta

Nihei

Abe

et al. 2006

Microbiology and Immunology

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Subacute sclerosing panencephalitis (SSPE) virus, a measles virus (MeV) mutant, was isolated from brain tissues of a patient shortly after the clinical onset, and the entire viral genome was sequenced. The virus, named SSPE‐Kobe‐1, formed syncytia on B95a and Vero/SLAM cells without producing cell‐free infectious virus particles, which is characteristic of SSPE virus. Phylogenetic analysis classified SSPE‐Kobe‐1 into genotype D3. When compared with an MeV field isolate of the same genotype (Ich‐B strain), SSPE‐Kobe‐1 exhibited mutation rates of 0.8–1.6% at the nucleotide level in each of the protein‐coding regions of the viral genome. It is noteworthy that the mutation rate of the M gene (1.2%) of SSPE‐Kobe‐1 was considerably lower than for other SSPE virus strains reported so far, but that the majority of the mutations (75%) were the uridine‐to‐cytidine biased hypermutation characteristic of the SSPE virus M gene. At the amino acid level, the viral proteins, such as N, P., C, V, M., F, H and L proteins, had point‐mutations on 3, 7, 1, 4, 3, 9, 8 and 14 residues, respectively, compared with the Ich‐B strain. In addition, the F and H proteins had mutated C‐termini due to single‐point mutations near or at the stop codons. Two of the three mutations in the M protein were Leu‐to‐Pro mutations, which are likely to affect the conformation and, therefore, the function of the protein. Because of the relatively small number of mutations, SSPE‐Kobe‐1 would be a useful tool to study genetic evolution of SSPE virus.

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Characterization of measles virus strains causing SSPE: A study of 11 cases

Cited by 74 publications

References 42 publications

Morbilliviruses and human disease

Morbilliviruses and human disease

Screening Random Peptide Libraries with Subacute Sclerosing PanencephalitisBrain-Derived Recombinant Antibodies Identifies Multiple Epitopes in the C-Terminal Region of the Measles Virus Nucleocapsid Protein

Full‐Length Sequence Analysis of Subacute Sclerosing Panencephalitis (SSPE) Virus, a Mutant of Measles Virus, Isolated from Brain Tissues of a Patient Shortly after Onset of SSPE

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