Eleven subacute sclerosing panencephalitis (SSPE) cases diagnosed in the UK between 1965 and 2000 were investigated. The entire or partial matrix (M), hemagglutinin (H), and nucleoprotein (N) genes of measles virus (MV) were sequenced following direct RT-PCR amplification from brain tissues. All the M genes showed the characteristic biased hypermutations and a premature termination codon was detected in 5/11 M sequences. Based on the more highly conserved H and N genes observed in persistent MV studies, phylogenetic analysis showed that two of three strains from patients likely to have acquired infection in the 1950s were related to clade C (WHO designation) and one appears to be a novel genotype. Three strains from patients infected in the 1960s and 1970s were clearly related to a MV strain isolated in 1974 belonging to genotype D1. Four strains from patients infected in the 1980s clustered with genotype D7 strains. One sequence from a patient infected in 1990s was identified as genotype D6. No vaccine strains were detected although five of these patients had been previously immunized. The sequence data obtained from these historic strains do not support the view that vaccine strains are associated with SSPE and provide valuable information for further studies of MV epidemiology, evolution, and pathogenesis in SSPE.

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Hantaan virus (HTNV) is the prototype species of the genus Hantavirus and has remained the epidemiologically most important species in the genus until now. Hantaviruses form a separate genus within the family Bunyaviridae, forming a group of closely related negative-stranded RNA viruses (4,17,25,29). Hantaviruses are the causative agents of hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome. HFRS occurs mainly in Europe and Asia and is associated with HTNV, Seoul virus (SEOV), Dobrava virus (DOBV), and Puumala virus (PUUV) infections (34). Usually, hantavirus pulmonary syndrome is found in the New World, where most of the cases are caused by the Sin Nombre virus (SNV) and Andes virus (ANDV) serotypes (8,11,15). Hantaviruses are transmitted to humans through the aerosol excreta of infected small mammals, mainly wild rodents (17). In China, HTNV together with SEOV accounts for at least 100,000 cases of hantavirus-associated HFRS each year. Approximately 150,000 HFRS cases occur annually worldwide. HTNV infection is characterized by fever, renal dysfunction, and in some cases, hemorrhagic manifestations (9,10,12,13,15).Hantaviruses have a tripartite genome that encodes a nucleocapsid protein (N protein), two envelope glycoproteins, and a viral RNA polymerase (30). The viral N protein elicits a strong humoral immune response in infected patients and immunized animals and has been extensively used to produce reagents for the diagnosis of hantavirus infections (1, 14, 21). Comparison of the amino acid sequences of five amino-terminal immunogenic regions of the N proteins of the HTNV, SEOV, and DOBV hantaviruses shows that they have high degrees of homology. Rabbit polyclonal sera produced against cell culture-grown virus and recombinant viral proteins were tested for their responses to five hantavirus antigens. Two types of antibody responses were generated; hence, two groups of sera could be distinguished, with HTNV, SEOV, and DOBV be attributed to the first group and SNV and PUUV to the second group (3). Schmidt and coworkers (31) investigated the cross-reactivity of rabbit sera raised against the N proteins of SEOV and other hantaviruses. The N-protein-specific antibodies induced by natural infection in human and experimental infections and immunizations have been found to be highly cross-reactive among the different hantaviruses (16,26,31). The N-protein-specific antibody titers in SEOV N-protein-immunized rabbits were only slightly lower than those in rabbits immunized with the N protein of the closely related HTNV and much lower than those in rabbits immunized with the N proteins of PUUV, SNV, and ANDV. Similarly, the anti-