Coronavirus infection and demyelination. Sequence conservation of the S-gene during persistent infection of Lewis-rats.
Adv Exp Med Biol
; 440: 767-73, 1998.
Article
em En
| MEDLINE
| ID: mdl-9782356
ABSTRACT
Coronaviruses display a large phenotypic variability, which may be an important factor for diversification and selection. Previous studies have demonstrated that the S-protein is an essential determinant of virulence and pathogenicity. Therefore we studied the S-gene as an indicator molecule for selection processes employing two different MHV-JHM variants. First, Lewis-rats were infected with MHV-JHM-Pi, a variant that causes demyelinating disease after several weeks p.i. It was not possible to isolate infectious MHV-JHM-Pi from such rats, although viral proteins were expressed. The S-gene was rescued directly from brain tissue employing RT-PCR technology. The amplicons were sequenced in bulk or at the level of single clones. We detected no evidence for an increase of S-gene mutants during the length of time. Only few mutations were found at the clonal level. The changes were distributed throughout the analysed S-gene fragments without a predilection in their location. The frequency of mutation remained low within a range of 0.03 to 0.5 mutations per thousand nucleotides. As a second approach, we sequenced the S-genes of viruses isolated from brain tissue infected with MHV-JHM-ts43. Infection of adult Lewis rats with that mutant resulted several weeks to months p.i. in demyelinating encephalomyelitis. The S-gene of this virus contains an insertion of 423 bp in the S1 region, which is identical to a polymorphic region described for MHV-4. In contrast to JHM-Pi, infectious MHV-JHM-ts43 was readily to isolate from brain tissue. The S-gene sequences of virus isolated 45-106 days p.i. from diseased rats were identical with that of the input virus. These results show, that during a persistent infection of Lewis-rats the S-gene was highly conserved.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glicoproteínas de Membrana
/
Proteínas do Envelope Viral
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Doenças Desmielinizantes
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Infecções por Coronavirus
/
Vírus da Hepatite Murina
Limite:
Animals
Idioma:
En
Revista:
Adv Exp Med Biol
Ano de publicação:
1998
Tipo de documento:
Article