Effect of the alterations in the fusion protein of measles virus isolated from brains of patients with subacute sclerosing panencephalitis on syncytium formation.

Measles virus (MV) is the causative agent of subacute sclerosing panencephalitis (SSPE) and viruses isolated from brains of the patients contain numerous mutations. We have previously demonstrated that the hemagglutinin (H) protein of MV SSPE strains can interact with the signaling lymphocyte activation molecule (SLAM) and an unidentified molecule on Vero cells, but not with CD46, as a receptor. The mechanism by which MV SSPE strains can induce cell-cell fusion in SLAM-negative Vero cells is not understood. We report here on the effect of mutations in the fusion (F) proteins of three MV SSPE strains on syncytium formation. The F proteins of the three SSPE strains were functional and co-expression with H protein from the MV wild-type or SSPE strains in this study induced formation of large syncytia in Vero cells as well as in cell lines expressing SLAM or CD46. Expression of chimeric F proteins of SSPE strains showed that amino acid substitutions in the F protein extracellular as well as cytoplasmic domain contributed to enhanced cell-cell fusion in Vero cells. These findings suggest a common molecular mechanism and a key role of the F protein for syncytium formation in cells expressing an unidentified third receptor for MV.

[Autoantibodies against glutamate receptors in patients with encephalitis].

We examined autoantibodies against GluRepsilon2 in patients with acute encephalitis, who were categorized into localized encephalitis and widespread encephalitis. Patients with localized encephalitis are defined as patients showing psychic symptoms (illusions, anxiety and distraction etc.), solitary seizures and/or very mild impairment of consciousness in the initial stage. Patients with widespread encephalitis are defined as patients showing a profound loss of consciousness and or convulsive status in the initial stage. In 24 patients with localized encephalitis, immunoglobulin (Ig) M autoantibodies against GluRepsilon2 tended to appear in CSF in the acute stage (0-20 days after onset of neurological symptoms) or recovery stage (21-60 days after onset of neurological symptoms) of encephalitis. In 22 patients with widespread encephalitis, IgM autoantibodies against GluRepsilon2 in CSF tended to appear in the recovery stage (21-60 days after onset of neurological symptoms) or chronic stage (>60 days after onset of neurological symptoms) of encephalitis. All patients with localized encephalitis had autoantibodies to the extracellular N epitope. However, no patients with widespread encephalitis had autoantibodies to the extracellular N epitope in acute stages. These data may suggest that GluR autoimmunity contributes to the onset of localized encephalitis.

[A child with non-herpetic acute limbic encephalitis affecting the claustrum and hippocampus].

We experienced an 8-year-old-boy with non-herpetic acute limbic encephalitis (NHALE), who developed headache, convulsion, consciousness disturbance, and ataxia following cold like symptoms. Disturbance of short term memory and a change of character were recognized. Myoclonic seizures and generalized tonic clonic convulsions developed, that responded to antiepileptic agents. Although other symptoms resolved spontaneously, short term memory disturbance persisted. Brain MRI demonstrated the lesion involving the bilateral claustrum and right hippocampus. Three months later, the lesion in the claustrum disappeared, but the hippocampus still showed slight hyperintensity on FLAIR image of MRI. Autoantibodies against glutamine receptor were detected in the cerebrospinal fluid and plasma, which suggested the involvement of immunologic disturbances in this disease. In NHALE, many cases have been reported in adults but not in children, and the further attentions should be paid to childhood-onset NHALE.

Biased hypermutation occurred frequently in a gene inserted into the IC323 recombinant measles virus during its persistence in the brains of nude mice.

Measles virus (MV) is the causative agent of measles and its neurological complications, subacute sclerosing panencephalitis (SSPE) and measles inclusion body encephalitis (MIBE). Biased hypermutation in the M gene is a characteristic feature of SSPE and MIBE. To determine whether the M gene is the preferred target of hypermutation, an additional transcriptional unit containing a humanized Renilla reniformis green fluorescent protein (hrGFP) gene was introduced into the IC323 MV genome, and nude mice were inoculated intracerebrally with the virus. Biased hypermutation occurred in the M gene and also in the hrGFP gene when it was inserted between the leader and the N gene, but not between the H and L gene. These results indicate that biased hypermutation is usually found in a gene whose function is not essential for viral proliferation in the brain and that the location of a gene in the MV genome can affect its mutational frequency.