Molecular mechanism of persistent infection of SSPE virus

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Subacute sclerosing panencephalitis (SSPE) is a chronic progressive disease of the central nervous system (CNS) caused by a persistent infrction of measles virus or a variant of measles virus. In this study, RT-PCR (Reverse transcription-coupled polymerase chain reaction) and cDNA cloning were used to examine the matrix (M) protein gene of measles virus in the brain and lymph node from a case of SSPE.In the examination of the brain, ten independent clones of the entire length of the coding region of the M protein gene were sequenced. The identical multiple mutations were revealed in 57 of 1008 nucleotides in comparison with Edmonston strain of measles virus. Ninety-three percent of these mutations was transition (U to C and A to G), so-called biased hypermutation. The nucleotide differences resulted in amino acid changes with considerable frequency. The M protein of all clones was found to terminate prematurely due to a nonsense mutation at codon 114 although the initiation codon was preserved. In the lymph node, twelve clones had identical mutations with brain clones and had 2 to 19 additional mutations. In 8 out of 12 clones, the termination point of the M protein was found to change due to the other nonsense mutation at codon 296. Another five major structural protein genes (NP,P,F,HA and L) were also detected in both brain and lymph node in our case. These findings suggest that in addition to the central nervous system, the lymph node may also have a role in the progression of SSPE.