Acute Infections with Rare Late Complications Subacute Sclerosing Panencephalitis

The paradigm of persistent infection characterized by an acute infection with rare late complications is subacute sclerosing panencephalitis (SSPE), an invariably fatal complication occurring 1-10 years after recovery from measles (Table 10-1). It occurs in only 1 in 300,000 cases and has become very rare indeed following the reduction in measles itself by widespread immunization of children. Nevertheless, it remains of great interest because of the light it sheds on the pathogenesis of persistent infections in the brain.

Patients with SSPE reveal very little measles virus in the brain but exceptionally high titers of neutralizing antibodies in cerebrospinal fluid. The RNA viral genome is detectable in neurons by nucleic acid hybridization, and nu-cleocapsids are demonstrable by electron microscopy and immunofluorescence. Studies on infected neurons in culture indicate that, in the presence of high-titer neutralizing antibody, antigenic modulation brings about a pronounced inhibition of transcription from the viral genome. Even in the absence of antibody it is clear that there is something peculiar to neurons, and/or their state of differentiation, which down-regulates transcription from the measles viral RNA. Transcription from paramyxovirus genomes characteristically displays polarity, that is, a progressive decline in efficiency of transcription as the polymerase progresses from the 3' to the 5' end of the genome. This gradient is much steeper in neurons infected with measles virus, with the result that the production of the envelope proteins, M, F, and H, is reduced and the L protein is hardly made at all. Thus, virtually no infectious virions are assembled, but there is sufficient transcription of the 3' "housekeeping" genes, N and P/C, to permit viral RNA replication and transfer of nucleocapsids at a very slow rate from cell to cell. Further, during the long incubation period of SSPE, numerous mutations accumulate, seen particularly in the M gene transcripts. All in all, SSPE illustrates beautifully how peculiarities of particular viruses and their host cells may conspire to provide conditions enabling the viral genome to persist—in this case, to the detriment of the host.

Was this article helpful?

0 0

Post a comment