Replication of dengue virus type 2 in human monocyte-derived macrophages: Comparisons of isolates and recombinant viruses with substitutions at aminoacid 390 in the envelope glycoprotein

The severity of dengue virus infection ranges from mild fever to dengue hem orrhagic fever and shock syndrome. The association of disease severity with virus replication in monocyte-derived macrophages (MDMs) was examined for dengue virus type 2 (DEN-2) isolates from Asia or America. Additionally, we constructed DEN-2 recombinant viruses with substitutions at residue 390 in the envelope glycoprotein (E390) because this residue is linked with the r egion of virus origin. Comparisons of virus yields of 3 isolates failed to show a correlation with clinical disease. However, the American strain did not replicate as well as the 2 Asian strains. For the recombinant viruses, substitution of Asn (Asian) at E390 with Asp (American) resulted in decreas ed ability to replicate in MDMs. These results are consistent with the prop osal that the lack of association of native American DEN-2 strains with sev ere disease is linked to reduced ability to replicate in MDMs, and that Asp at E390 may contribute to this reduction.