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Dengue viruses comprise a group of four serotypes within the Flaviviridae, a family of closely related viruses transmitted by mosquitoes and ticks (1). These viruses produce enveloped particles containing a single positive stranded RNA genome of approximately 11 kb, which codes for three structural (C, prM/M, E) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5) (2). The size and functions of the virion structural proteins have been characterized (3, 4), however little is known about the non-structural region. Although several sequence motifs have been identified which suggest specific functions for a number of die NS proteins (5, 3), die only one confirmed to date is the protease activity of NS2B -NS3 (6). The function of the NS1 protein is still unknown, however evidence supports a role in virion assembly and maturation (7) and it seems associated with die viral replicase complex (8). In addition, it is unusual for a non structural viral protein in that it is boui glycosylated (9) and a major protective antigen (10). Dengue viruses continue to cause major epidemics throughout the tropical and sub-tropical regions of the world with no efficient vaccine against the four serotypes being currently available. Candidate live attenuated dengue virus vaccines have however been derived from wild-type isolates by repeated passage in cell culture (11, 14). Although the basis of attenuation is unknown, by comparing genome sequences of these isolates and their culture derivatives, it may be possible to determine molecular markers of virulence. The dengue virus type 2 (DEN-2), strain PR159, was isolated in Puerto Rico (1969) from a patient widi dengue fever and subsequendy passaged 19 times in cell culture (12, 13). This PR-159-S1 strain is a small-plaque, temperature-sensitive derivative, which exhibits reduced virulence for suckling mice and is markedly attenuated in rhesus monkeys. The complete genome sequence of die PR-159-S1 strain has been previously reported (15). We report here the sequence of die gene encoding NS1 of the parental PR-159 strain.

Sequence of the dengue virus type 2 (strain PR-159) NS1 gene and comparison with its vaccine derivative