Single amino acid changes in the mumps virus haemagglutinin-neuraminidase and polymerase proteins are associated with neuroattenuation.

It has previously been shown that three amino acid changes, one each in the fusion (F; Ala/Thr-91-->Thr), haemagglutinin-neuraminidase (HN; Ser-466-->Asn) and polymerase (L; Ile-736-->Val) proteins, are associated with attenuation of a neurovirulent clinical isolate of mumps virus (88-1961) following serial passage in vitro. Here, using full-length cDNA plasmid clones and site-directed mutagenesis, it was shown that the single amino acid change in the HN protein and to a lesser extent, the change in the L protein, resulted in neuroattenuation, as assessed in rats. The combination of both amino acid changes caused neuroattenuation of the virus to levels previously reported for the clinical isolate following attenuation in vitro.

Astrocytes play a key role in activation of microglia by persistent Borna disease virus infection.

Neonatal Borna disease virus (BDV) infection of the rat brain is associated with microglial activation and damage to certain neuronal populations. Since persistent BDV infection of neurons is nonlytic in vitro, activated microglia have been suggested to be responsible for neuronal cell death in vivo. However, the mechanisms of activation of microglia in neonatally BDV-infected rat brains remain unclear.

A single nucleotide change in the mumps virus F gene affects virus fusogenicity in vitro and virulence in vivo.

Mumps virus is highly neurotropic, with evidence of infection of the central nervous system in more than half of clinical cases. In the prevaccine era, mumps was a major cause of viral meningitis in most developed countries. Despite efforts to attenuate the virus, some mumps vaccines have retained virulence properties and have caused aseptic meningitis in vaccinees, resulting in public resistance to vaccination in some countries.

Functional consequences of attenuating mutations in the haemagglutinin neuraminidase, fusion and polymerase proteins of a wild-type mumps virus strain.

Wild-type mumps viruses (MuVs) are highly neurotropic and, prior to widespread vaccination programmes, were a major cause of viral meningitis and encephalitis in most developed countries. At present, there are no markers for virus attenuation, apart from the failure of a passaged isolate to produce clinical symptoms in vaccinees. Indeed, some MuV vaccines have retained residual neurovirulence properties and have caused aseptic meningitis in vaccinees.