RESUMO
The virulence of a yellow fever (YF) virus (P-16065) isolated from a fatal case of vaccine-associated viral encephalitis was investigated. P-16065 appeared identical to its parent vaccine virus (17D-204 USA, lot 6145) when examined with monoclonal antibodies except that YF wild type-specific MAb S24 recognized P-16065 but not 17D-204 USA 6145. Thus, a mutation of at least one epitope on the envelope (E) protein had occurred. Unlike 17D-204 USA 6145 and other 17D vaccine viruses, P-16065 was neuroinvasive and virulent for mice after intranasal inoculation, and neurovirulent for monkeys after intracerebral inoculation. The E protein of P-16065 differed from 17D-204 USA by two amino acids at positions 155 and 303. Changes at amino acid position 155 are found in other YF vaccine viruses that are not neurovirulent, and it is therefore postulated that the change at position 303 is involved in the alteration of the phenotype of P-16065 and may be important for virulence of YF virus.
Assuntos
Encefalomielite Aguda Disseminada/microbiologia , Vacinas Virais/efeitos adversos , Febre Amarela/microbiologia , Vírus da Febre Amarela/isolamento & purificação , Aedes/microbiologia , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/imunologia , Sequência de Bases , DNA Viral , Humanos , Macaca fascicularis , Camundongos , Dados de Sequência Molecular , Mucosa Nasal/microbiologia , Temperatura , Células Tumorais Cultivadas , Células Vero , Virulência , Febre Amarela/etiologia , Febre Amarela/imunologia , Vírus da Febre Amarela/patogenicidade , Vírus da Febre Amarela/fisiologiaRESUMO
Turkish tick-borne encephalitis (TTE) virus causes an acute form of meningoencephalomyelitis in sheep in the north-western region of Turkey. The clinical syndrome resembles louping ill (LI) and the viruses responsible for both LI and TTE are members of the tick-borne encephalitis (TBE) complex of the Flaviviridae. The envelope protein gene of TTE virus was reverse-transcribed, amplified, cloned and sequenced. Alignment of the resultant sequence with those from other viruses of the TBE complex reveals that TTE virus is more closely related, at both nucleotide and amino acid levels (84.6% and 96% respectively), to the Central European (CEE) subtype of the TBE virus, usually associated with human disease. The relationship with LI virus is more distant (83% and 93.5% respectively). These studies support the assertion that the ovine encephalomyelitis found in Turkey is caused by a virus that is genetically distinct from known strains of both LI and CEE viruses and from a number of other known viruses of the TBE complex.
