POSSIBLE OCCURRENCE OF A GENETIC BOTTLENECK IN DENGUE SEROTYPE-2 VIRUSES BETWEEN THE 1980 AND 1987 EPIDEMIC SEASONS IN BANGKOK, THAILAND

Cocirculation of two genetic subtypes of dengue serotype 2 viruses was first observed in the 1980 epidemic season in Thailand. To further de lineate the evolutionary history and the contribution of these subtype s to subsequent epidemics, we determined the envelope glycoprotein gen e sequence of 20 dengue serotype 2 viruses isolated from infected pati ents during 1987 and compared them with those derived from earlier yea rs. Subtype IIIa strains represented the majority (18 of 19) of dengue type 2 viruses derived from Bangkok metropolitan area, whereas all th ree strains from a province in the northeastern region belonged to sub type IIIb, indicating uneven local distribution of dengue subtypes wit hin the same year, Three types of sequence variation were identified i n both subtypes: substitutions that were unique to individual strains; substitutions that were shared among ail subtype IIIa or IIIb viruses of both the 1980 and 1987 epidemics; and those that were shared only among all subtypes IIIa or nib viruses of the 1987 epidemic, but were absent from the corresponding subtypes of 1980. While the first and se cond types of substitution were indicative of the most recent random m utations and previous mutations that had been fixed in virus populatio ns, respectively, the third type suggested possible occurrence of a ge netic bottleneck and subsequent expansion of one or a limited number o f subtype IIIa strains in Bangkok between 1980 and 1987. Immunoblot an alysis of intracellular NS1 antigen with anti-NS1 monoclonal antibodie s also revealed antigenic heterogeneity of the NS1 protein that correl ated with the subdivision based on envelope protein variation.