................................................ SHORT COMMUNICAT ION A single nucleotide change in the E protein gene of dengue virus 2 Mexican strain affects neurovirulence in mice

were selected by the size of their lytic plaques. Nucleotide sequences of the clones producing large plaques (D2ML2, D2ML:3 and D2ML4) revealed 11 mutations, 10 of which were silent. The substitution at nucleotide 1168 (G- ~ C) generates one amino acid difference at residue:390 (Asp- ~ His) of the envelope protein (E). These clones showed high virulence in suckling mice when inoculated intra-cerebrally ( ~ 70 % mortality). However, the clones which showed small lyric plaques (D2MS1, D2MS2 and D2MS4) displayed a substitution from Asp-~ Asn at the same position and had attenuated virulence. Based on these data, we suggest that substitution of Asp- ~ His at residue:390 perhaps affects a functionally important structural element that could be a determinant of dengue neuro-virulence. This substitution falls in domain III of the E protein, which plays an important role in viral binding; therefore, we propose that the substi-tution affects virulence and cellular tropism. Dengue is caused by four different serotypes of the dengue virus. Dengue fever (DF) is an acute, mosquito-transmitted viral disease characterized by fever, headache, arthralgia, myalgia and rash; however, some patients manifest severe clinical symptoms of haemorrhage (dengue haemorrhagic fever; DHF) and shock (dengue septic shock; DSS)(Monath, 1986). It has been proposed that immunopathological mech-anisms play important roles in the development ofDHF/DSS (Halstead, 1988). Rosen (I977) has proposed that DHF/DSS is caused by dengue virus variants of increased pathogenic potential. The potential importance of natural variation among dengue viru