Molecular mechanism of persistent infection of SSPE virus

亚急性硬化性全脑炎（SSPE）是一种慢性进行性中枢神经系统（CNS）疾病，由麻疹病毒或麻疹病毒的变异体引起的持续性梗死。本研究应用逆转录-聚合酶链反应（RT-PCR）和cDNA克隆技术对1例SSPE患儿脑组织和淋巴结组织中麻疹病毒基质（M）蛋白基因进行了检测，并对脑组织M蛋白基因编码区10个独立克隆进行了测序。在1008个核苷酸中，有57个核苷酸与Edmonston株麻疹病毒的核苷酸序列发生了相同的多重突变。这些突变中有93%是过渡（U到C和A到G），即所谓的偏倚超突变。核苷酸的差异导致了氨基酸的变化与相当大的频率。发现所有克隆的M蛋白由于密码子114处的无义突变而过早终止，尽管起始密码子被保留。在淋巴结中，12个克隆具有与脑克隆相同的突变，并且具有2至19个额外的突变。在12个克隆中的8个中，发现M蛋白的终止点由于密码子296处的其他无义突变而改变。另外5个主要结构蛋白基因（NP、P、F、HA和L）在我们的病例中也在脑和淋巴结中被检测到。这些发现表明，除了中枢神经系统，淋巴结也可能在SSPE的进展中发挥作用。

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.